Dissertations / Theses: 'Potential Scaffolds'

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Hed, Yvonne. "Multifunctional Dendritic Scaffolds: Synthesis, Characterization and Potential applications." Doctoral thesis, KTH, Ytbehandlingsteknik, 2013. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-127429.

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The development of materials for advanced applications requires innovative macromolecules with well-defined structures and the inherent ability to be tailored in a straightforward manner. Dendrimers, being a subgroup of the dendritic polymer family, possess properties which fulfill such demands. They have a highly branched architecture with a high number of functional groups and are one of the most well-defined types of macromolecules ever synthesized. However, despite their well-defined nature and high functional density, traditional dendrimers commonly lack diverse chemical functionalities. Therefore, this thesis focuses on the synthesis of more complex dendritic materials to extend their tailoring capacity by introduction of dualfunctionalities for multipurpose actions. It covers the synthesis of dualfunctional dendrimers, dendritic modification of linear poly(ethylene glycol) polymers and cellulose surfaces, and the synthesis of linear dendritic hybrids. The building blocks enabling this synthesis, AB2C monomers, were also developed during this work. The orthogonal nature between click groups (azide, alkyne and alkene) and hydroxyl groups have efficiently been utilized for postfunctionalization by robust click chemistry and traditional esterification reactions. Furthermore, linear dendritic hybrids were synthesized, merging the properties of linear and dendritic macromolecules. The dendritic frameworks were tailored towards the production of bone fracture adhesives, novel biofunctional dendritic hydrogels, biosensors and micellar drug delivery vehicles.
Utveckling av material för avancerade applikationer kräver innovativa makromolekyler med väldefinierade strukturer och som kan skräddarsys på ett enkelt sätt. Dendrimerer är en undergrupp av dendritiska polymerer vars egenskaper uppfyller dessa krav. De har en mycket förgrenad arkitektur med många funktionella grupper och är en av de mest väldefinierade befintliga syntetiska makromolekylerna. Trots dess väldefinierade karaktär och höga funktionalitet saknar ofta traditionella dendrimerer multipla kemiska funktionaliteter. Denna avhandling fokuserar därför på syntesen av mer komplexa dendritiska material för att förbättra deras kapacitet att skräddarsys, detta görs genom att introducera fler funktionaliteter som kan utnyttjas för multipla ändamål . Avhandlingen redogör för syntesen av difunktionella dendrimerer, dendritiska modifikationer av polyetylenglykol och cellulosaytor samt syntes av traditionella dendritiska hybrider. Byggstenarna som möjliggör syntesen, AB2C monomerer, framställdes också under detta arbete. Den ortogonala karaktären mellan klick grupper (azid, alkyn och alkene) och hydroxylgrupper har utnyttjats effektivt för funktionaliseringar genom användande av robust ”Click”-kemi och traditionella esterifikationsreaktioner. Vidare tillverkades de linjära dendritiska hybrider för att kombinera egenskaperna hos både linjära och traditionella dendritiska polymerer i en och samma makromolekyl. Samtliga dendritiska strukturer skräddarsyddes för applikationer så som benlimmer, biofunktionella dendritiska hydrogeler, biosensorer och läkemedels-bärande miceller.

QC 20130830

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Sharp, Duncan McNeill Craig. "Bioactive scaffolds for potential bone regenerative medical applications." Thesis, University of Edinburgh, 2011. http://hdl.handle.net/1842/9520.

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Fracture non-unions and bone defects represent a recalcitrant problem in the field of orthopaedic surgery. Although the current gold-standard treatment, autologous bone grafting, has a relatively high success rate, the technique is not without serious problems. The emerging field of regenerative medicine may have the potential to provide an alternative treatment. One promising strategy involves the delivery of both cells and multiple growth factors with different release profiles. A range of scaffolds was developed from Poly( -caprolactone) (PCL), Poly(lactideco- glycolide) (PLGA), and two blends of PCL (Mn 42,500) and PLGA. The scaffolds were manufactured utilising a novel modified fused deposition modelling system, using polymer/dichloromethane solutions. The scaffolds were found to have pore sizes suitable for bone regenerative medical applications (373±9.5 μm in the Ydirection and 460±13 μm in the X-direction). However, the scaffolds were found to be only 52±3 μm in height. This means that the two-layer scaffolds were relatively flat. This was undesirable, as direct control of the complete 3D geometry was the favoured strategy, though it may not be a necessary requirement. Five scaffold coatings were also developed from alginate, chitosan (crosslinked using sodium hydroxide or tripolyphosphate), Type-I collagen and Type-A gelatin. The scaffold coatings were screened in vitro for their cell-compatibility with human marrow stromal cells (hMSCs), human osteoblasts and MG63 cells. This was assessed using an assay for cell death, and assessing total cell counts. From these studies, Type-I collagen was found to be the optimum coating. For hMSCs, their death rates were found to be 19.1±6.3% for alginate, 5.3±3.6% and 2.9±1.4% for chitosan crosslinked with tripolyphosphate and sodium hydroxide respectively, compared to 0.11±0.07% for Type-I collagen, and 0.15±0.13% and 0.16±0.12% for 0.1% and 0.2% gelatin respectively. Type-I collagen was found to be the most cellcompatible coating, as it was consistently associated with higher cell counts than Type-A gelatin. Similarly, PCL scaffolds vacuum dried for 1 hr were found to be cell-compatible. No detectable clinically significant difference was found in either total cell counts, or the proportion of cell death in; hMSCs exposed to PCL scaffolds processed with dichloromethane, hMSCs either exposed to scaffolds known to be biocompatible, or hMSCs cultured in the absence of scaffolds. When cell morphology was compared, scaffolds vacuum dried for 1 hr or more were found to have a similar morphology to the cells cultured in the absence of scaffolds. It was therefore concluded that a vacuum drying time of 1 hr was sufficient for cell-compatibility. The scaffold materials were screened both for their encapsulation efficiencies and release characteristics using the model drug, methylene blue. The encapsulation efficiency was found to be both relatively high and consistent for both Mn 42,500 and 80,000 PCL as well as PCL:PLGA 66:33, at 71±6%, 71±5%, and 78±10% respectively, relative to the low efficiencies recorded for both PCL:PLGA 66:33 and PLGA: 57±5% and 38±10% respectively. The release rate of methylene blue from PCL (Mn 42,500), was found to be relatively slow, controlled, and consistent between batches (between 21±2% and 20±3% released in the first 24 hr). Despite the release rate being consistent for PCL (Mn 80,000), the release rate was thought to be too high, since between 29±3% and 39±5% of the test compound was released in the first 24 hr period. The release rate of methylene blue from the PCL/PLGA blends (between 17±2% – 30±7% and 18±4% – 31±6% in the first 24 hr) and PLGA (between 7.1±3.4% – 9.3±2.9% in the first 24 hr) were found to be inconsistent, and low in the case of PLGA, even taking the different loading efficiencies into account. Therefore, PCL (Mn 42,500) was selected as the favoured candidate scaffold material. The loading content and release profiles from methylene blue loaded collagen scaffold coatings were also evaluated. The drug loading capacity was found to be suitable for use as a drug delivery system (65±5 μg/g of methylene blue per unit scaffold mass). The release of methylene blue was observed to be rapid (between 54±10% – 70±17% in the first 24 hr), which was thought to be desirable for the coating delivery system. Recombinant human bone morphogenetic protein-7 (rhBMP-7) was used as a representative growth factor of interest for bone regenerative medical applications. It was loaded in collagen scaffold coatings (CoatBMP 1.25) and encapsulated within PCL (Mn 42,500) scaffolds (ScaffBMP 1.25). Control coatings and scaffolds were designated CoatPBS and ScaffPBS respectively. Both delivery systems were found to release detectable quantities of rhBMP-7 (releasing 2.8±0.2 μg/g and 87±7 ng/g respectively in the first 24 hr), even after 14 days. The release rate of the growth factor from the scaffold coating was higher than that from the encapsulating scaffolds. However, the cumulative release profiles were found to deviate from the desired ideal release profiles, and burst release was observed from both delivery systems. Although differences were observed for the two delivery systems, this difference may not be of clinical significance. Nevertheless, scaffolds with less than ideal delivery properties may still be of potential clinical use. The bioactivity of the rhBMP-7 released from the test scaffolds was therefore assessed by quantifying the area of normalised ALP staining of hMSCs. The release of rhBMP-7 from the collagen coating of the PCL (Mn 42,500) scaffolds (CoatBMP 1.25ScaffPBS) was capable of statistically significantly increasing hMSC normalised ALP expression, although the actual differences were often relatively small. Therefore, at least a proportion of the growth factor released is likely to have been bioactive. The release from scaffolds encapsulating rhBMP-7 (CoatPBSScaffBMP 1.25) did not have this effect on the hMSCs, indicating that either the concentration released was too low, or the growth factor released was no longer bioactive. However, when the cells were seeded directly onto the scaffolds, the activity of ALP, normalised by a DNA assay, was statistically significantly increased for the CoatPBSScaffBMP 1.25 scaffolds, in hMSCs from all three test patient donors (by 35±10% on the control). ALP activity was also significantly increased in hMSCs from two of the three patients seeded onto CoatBMP 1.25ScaffBMP 1.25 scaffolds (by 39±10% on the control). ALP activity was only statistically significantly increased for one of the hMSC patients when seeded onto CoatBMP 1.25ScaffPBS scaffolds (by 35±14% on the control). The functional osteoinductive capacity of Type-I collagen coated PCL (Mn 42,500) scaffolds loaded with rhBMP-7 was assessed using C2C12 cells seeded onto the scaffolds, and quantified using qRT-PCR. The genes of interest were; Type-I collagen (Col1), osteopontin (OP), ALP, osteocalcin (OC) and runt related transcription factor 2 (Runx2). The CoatBMP 1.25ScaffPBS scaffolds had an early osteoinductive effect on the C2C12 cells, as ALP, OC and Runx2 were elevated during the first 2 days only, compared to the control (e.g. by 44±12%, 128±42%, 60±25% and 46±25% respectively at the 24 hr mark). The CoatPBSScaffBMP 1.25 scaffolds also had an osteoinductive effect on the cells, which was more sustained than that observed for the CoatBMP 1.25ScaffPBS group. While OP, ALP and Runx2 were up-regulated in the first 24 hr compared to the control (by 38±10%, 208±82% and 72±31% respectively), statistically significant up-regulation of the late marker OC was delayed until the 48 hr mark (by 73±49%). The effect was found to be sustained until day 7, when OC and Runx2 were both statistically significantly up-regulated compared to the control (by 151±91% and 93±27% respectively). The CoatBMP 1.25ScaffBMP 1.25 scaffolds were found to combine the early effect of the CoatBMP 1.25ScaffPBS scaffolds, with the more sustained effect of the CoatPBSScaffBMP 1.25 scaffolds. ALP, OC and Runx2 were all up-regulated at the 24 hr mark (by 312±56%, 329±39% and 96±25% respectively). This osteoinductive effect was sustained until day 7 when Col1, ALP and Runx2 were still up-regulated compared to the control (by 174±78%, 72±24% and 178±78% respectively). These data suggest that the scaffolds containing rhBMP-7 have a weak osteoinductive effect on the cells seeded onto them. The different delivery systems were found to affect the cells differently. The clinical significance of this was not assessed in these studies. 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) was used as a model drug to assess the feasibility of releasing lipid-soluble active factors from the scaffolds. This was assessed by quantifying the area of normalised ALP staining of hMSCs. The release of 1,25(OH)2D3 from the loaded collagen scaffold coatings and the encapsulating scaffolds significantly increased ALP expression compared to the control scaffold groups (by 115±28% and 69±25% respectively). Furthermore, ALP expression was significantly increased when the two delivery systems were used together, when compared to either delivery system on its own. These data suggest that the delivery of lipid-soluble active factors is feasible from collagen coated PCL scaffolds, and that the coating and encapsulating delivery systems are mutually compatible.

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Aduba, Donald C. Jr. "Multi-platform arabinoxylan scaffolds as potential wound dressing materials." VCU Scholars Compass, 2015. http://scholarscompass.vcu.edu/etd/3955.

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Biopolymers are becoming more attractive as advanced wound dressings because of their naturally derived origin, abundance, low cost and high compatibility with the wound environment. Arabinoxylan (AX) is a class of polysaccharide polymers derived from cereal grains that are primarily used in food products and cosmetic additives. Its application as a wound dressing material has yet to be realized. In this two-pronged project, arabinoxylan ferulate (AXF) was fabricated into electrospun fibers and gel foams to be evaluated as platforms for wound dressing materials. In the first study, AXF was electrospun with varying amounts of gelatin. In the second study, AXF was dissolved in water, enzymatically crosslinked and lyophilized to form gel foams. The morphology, mechanical properties, porosity, drug release kinetics, fibroblast cell response and anti-microbial properties were examined for both platforms. Carbohydrate assay was conducted to validate the presence of arabinoxylan ferulate in the electrospun GEL-AXF fibers. Swelling and endotoxin quantification studies were done to evaluate the absorptive capacity and sterilization agent efficacy respectively in AXF foams. The results indicated successful fabrication of both platforms which validated the porous, absorptive, biocompatibility and drug release properties. The results also exhibited that silver impregnated AXF scaffolds inhibited growth of Pseudomonas aeruginosa, Staphylococcus aureus and Enterococcus faecalis bacteria species, anti-microbial properties necessary to function as advanced wound dressing materials. Future work will be done to improve the stability of both platforms as well as evaluate its applications in vivo.

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Mohammadzadehmoghadam, Soheila. "Electrospun Silk Nanofibre Mats and Their Potential as Tissue Scaffolds." Thesis, Curtin University, 2018. http://hdl.handle.net/20.500.11937/77169.

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In this study new electrospun silk fibroin (SF) based scaffolds were developed and their material and biocompatibility characteristics evaluated. Three types of SF based scaffolds were generated: SF/halloysite (HNT), SF/gelatin and SF/collagen. Scaffolds chosen for their material and biocompatibility characteristics were coated with fibroblast extracellular matrix and their efficacy for supporting primary human keratinocyte expansion were investigated. Collectively these data indicated SF/HNT scaffolds have merit for wound healing and tissue engineering applications.

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Sisson, Kristin M. "Investigating the potential of electrospun gelatin and collagen scaffolds for tissue engineering applications." Access to citation, abstract and download form provided by ProQuest Information and Learning Company; downloadable PDF file, 133 p, 2010. http://proquest.umi.com/pqdweb?did=1993336301&sid=9&Fmt=2&clientId=8331&RQT=309&VName=PQD.

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Carlqvist, K. H. "The potential of muscle-derived progenitors on titanium scaffolds in bone regenerative applications." Thesis, University College London (University of London), 2011. http://discovery.ucl.ac.uk/1301768/.

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Muscle-derived cells (MDCs) are a heterogeneous population consisting of cells that can undergo myogenic differentiation; however, it has emerged that not all MDCs are restricted to the myogenic lineage. This discovery may have many implications; for example, MDCs may be a suitable alternative source of osteogenic cells for bone repair. The currently accepted treatment for bone repair, bone grafting, is often associated with small amount of obtainable bone. Much of the work published regarding the differential potential of MDCs has not, to date, focused on the osteogenic pathway and even fewer studies have been performed on human cells. In this thesis osteogenic MDCs were isolated by differential adhesion to fibronectin (Fn) i.e. MDCsFn and compared with mesenchymal stem cells (MSCs) in relation to their osteogenic potential. The osteogenic potential was assessed by measuring mineralization and relevant gene- and protein- expression. MSCs and MDCsFn had a similar pattern of ALP activity and expression. Furthermore, MSCs and MDCsFn both showed mineralization after 3 weeks measured by Alizarin Red S. A qPCR Array measuring the activity of 46 osteogenic genes also showed similarities in gene expression between the two cell types; however, the MSCs showed a more consistent pattern between patients, compared to MDCsFn. Titanium (Ti) has previously been used as a bone repair scaffold in humans due to its osteoconductivity. The interaction between Ti, of various roughness and hydrophilicity, and the two cell types, i.e. MSCs and MDCsFn, were assessed with relation to biocompatibility. Interestingly, the hydrophilic, rough surface, which has been described as superior in bone formation applications, showed higher levels of cell death, both apoptosis and necrosis, compared to the other tested surfaces for both cell types. In conclusion, due to the similarities between MDCsFn and MSCs there might be possibilities to use the osteogenic fraction in future bone regenerative applications.

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Bursey, Devan. "Ribosomally Synthesized and Post-Translationally Modified Peptides as Potential Scaffolds for Peptide Engineering." BYU ScholarsArchive, 2019. https://scholarsarchive.byu.edu/etd/8124.

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Peptides are small proteins that are crucial in many biological pathways such as antimicrobial defense, hormone signaling, and virulence. They often exhibit tight specificity for their targets and therefore have great therapeutic potential. Many peptide-based therapeutics are currently available, and the demand for this type of drug is expected to continue to increase. In order to satisfy the growing demand for peptide-based therapeutics, new engineering approaches to generate novel peptides should be developed. Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a group of peptides that have the potential to be effective scaffolds for in vivo peptide engineering projects. These natural RiPP peptides are enzymatically endowed with post-translational modifications (PTMs) that result in increased stability and greater target specificity. Many RiPPs, such as microcin J25 and micrococcin, can tolerate considerable amino acid sequence randomization while still being capable of receiving unique post-translational modifications. This thesis describes how we successfully engineered E. coli to produce the lasso peptide microcin J25 using a two-plasmid inducible expression system. In addition, we characterized the protein-protein interactions between PTM enzymes in the synthesis of micrococcin. The first step in micrococcin synthesis is the alteration of cysteines to thiazoles on the precursor peptide TclE. This step is accomplished by three proteins: TclI, TclJ, and TclN. We found that a 4-membered protein complex is formed consisting of TclI, TclJ, TclN, and TclE. Furthermore, the TclI protein functions as a central adaptor joining two other enzymes in the Tcl pathway with the substrate peptide.

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Adegoke, Yusuf Adeyemi. "Design and synthesis of new scaffolds as antiproliferative agents and potential hsp90 inhibitors." University of Western Cape, 2020. http://hdl.handle.net/11394/7722.

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Doctor Pharmaceuticae - DPharm
Natural products have been an important source of drugs and novel lead compounds in drug discovery. Their unique scaffolds have led to the synthesis of derivatives that continue to give rise to medicinally relevant agents. Thus, natural product-inspired drugs represent a significant proportion of drugs in the market and with several more in development. Cancer is among the leading public health problems and a prominent cause of death globally. Chemotherapy has been important in the management of this disease even though side effects that arise due to lack of selectivity is still an issue.

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Rodriguez, Isaac. "Mineralization Potential of Electrospun PDO-nHA-Fibrinogen Scaffolds Intended for Cleft Palate Repair." VCU Scholars Compass, 2010. http://scholarscompass.vcu.edu/etd/2111.

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The overall goal of this study was to identify mineralized scaffolds which can serve as potential alternatives to bone graft substitutes intended for cleft palate repair. The aim of this preliminary study was to evaluate the role of fibrinogen (Fg) and nano-hydroxyapatite (nHA) in enhancing mineralization potential of polydioxanone (PDO) electrospun scaffolds. Scaffolds were fabricated by blending PDO:nHA:Fg in the following weight ratios: 100:0:0, 50:25:25, 50:50:0, 50:0:50, 0:0:100 and 0:50:50. Scaffolds were immersed in different simulated body fluids for 5 and 14 days to induce mineralization. The inclusion of fibrinogen induced sheet-like mineralization while individual fiber mineralization was noticed in its absence. Modified protocols of alizarin red staining and burn-out test were developed to quantify mineral content of scaffolds. After mineralization, 50:50:0 scaffolds were still porous and contained the most mineral. 50:25:25 scaffolds had the highest mineralization potential but lacked porosity. Therefore, it can be anticipated that these mineralized organic-inorganic electrospun scaffolds will induce bone formation.

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Idahosa, Kenudi Christiana. "Bayliss-Hillman adducts as scaffolds for the construction of novel compounds with medicinal potential." Thesis, Rhodes University, 2012. http://hdl.handle.net/10962/d1006763.

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This project has focused on exploring the application of Baylis-Hillman (BH) {a.k.a. Morita-Baylis-Hillman (MBH)} scaffolds in the construction of various compounds with medicinal potential. A series of 2-nitrobenzaldehydes has been treated under BH conditions, with two different activated alkenes, viz., (MVK) and methyl acrylate, using (DABCO) or (3-HQ) as catalyst. While most of the BH reactions were carried out at room temperature, some reactions were conducted using microwave irradiation. The resulting BH adducts have been subjected to dehydration, conjugate addition and allylic substitution to obtain appropriate intermediates, which have been used in turn, to synthesize possible lead compounds, viz., cinnamate esters as HIV-1 integrase inhibitors, 3-(aminomethyl)quinolines and quinolones as anti-malarials and cinnamate ester-AZT conjugates as dual-action HIV-1 integrase-reverse transcriptase (IN-RT) inhibitors. Conjugate addition reactions of methyl acrylate-derived BH β-hydroxy esters with the amines, piperidine, propargylamine and 2-amino-5-(diethylamino)pentane, has afforded a range of products as diastereomeric mixtures in moderate to excellent yields. Catalytic hydrogenation of the aminomethy β-hydroxy esters derivatives, using a palladium-oncarbon (Pd-C) catalyst, has afforded the corresponding, novel 3-aminomethyl-2- quinolone derivatives in moderate yields. Effective allylic substitution reactions of the MVK-derived BH β-hydroxy ketones (via a conjugate addition-elimination pathway) using in situ-generated HCl has afforded the corresponding α-chloromethyl derivatives, which have been reacted with various amines, including piperidine, piperazine, propargylamine and 2-amino-5-(diethylamino)pentane, to yield α-aminomethyl derivatives. Catalytic hydrogenation of selected α-aminomethyl derivatives, using a Pd-C catalyst, has afforded the corresponding, novel 3- (aminomethyl)-2-methylquinoline derivatives in low to moderate yields. A bioassay, conducted on a 6-hydroxy-2-methyl-3-[(piperidin-1-yl)methyl]quinoline isolated early in the study indicated anti-malarial activity and prompted further efforts in the synthesis of analogous compounds. Reaction of the methyl acrylate-derived BH adducts with POCl3 has provided access to α-(chloromethyl)cinnamate ester derivatives, which have been aminated to afford α- (aminomethyl)cinnamate ester derivatives as potential HIV-1 integrase inhibitors. The α- (propargylaminomethyl)cinnamates were used, in turn, as substrates for the “click chemistry” reaction with 3'-azido-3'-deoxythymidine (AZT– an azide and an established reverse transcriptase HIV-1 inhibitor) to afford cinnamate ester-AZT conjugates as potential dual-action HIV-1 integrase-reverse transcriptase (IN-RT) inhibitors. Computer modelling and docking studies of a cinnamate ester-AZT conjugate into the HIV-1 integrase and reverse transcriptase active-sites revealed potential hydrogen-bonding interactions with amino acid residues within the receptor cavities. The isolated products have been appropriately characterized using IR, 1- and 2-D NMR and HRMS techniques, while elucidation of the stereochemistry of the double bond in the BH-derived halomethyl derivatives has been assigned on the basis of NOE, computer modelling and X-ray crystallographic data.

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Van, Heerden Esther. "Osseointegration potential for heat treated 3D Ti6Al4V scaffolds seeded with mysenchymal stem cells in vitro." Master's thesis, University of Cape Town, 2014. http://hdl.handle.net/11427/6012.

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Includes abstract.
Includes bibliographical references.
Aseptic loosening of artificial joints occurs due to the loss of implant fixation. By implementing a 3D porous structure at the bone-implant interface, the ingrowth of bone will permit better and stronger interlocking of the implant to prevent loosening. In this study, it is hypothesized that the seeding of 3D scaffolding structures with mesenchymal stem cells (MSCs) will improve the potential for osseointegration of the implants, as the existing bone may be more inclined to unite with developing bone than with the implant substrate. Titanium-6 Aluminium-4 Vanadium (Ti64) is one of the most commonly used implant materials. Heat treatment of Ti64 was seen in tests done at the University of Cape Town to further improve against implant failure by vastly improving the materials strength and reducing debris formation. Thus the aim of this study was to investigate the effects the heat treatment of Ti64 would have on the capabilities of seeded MSCs in vitro.

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Fox, Derek Bradford. "The potential roles of synoviocyte interactions with biological scaffolds in promoting avascular meniscal fibrocartilage regeneration /." Free to MU Campus, others may purchase, 2004. http://wwwlib.umi.com/cr/mo/fullcit?p3137698.

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Dey, Rebecca. "An investigation into the potential use of poly(vinylphosphonic acid-co-acrylic acid) in bone tissue scaffolds." Thesis, University of Manchester, 2017. https://www.research.manchester.ac.uk/portal/en/theses/an-investigation-into-the-potential-use-of-polyvinylphosphonic-acidcoacrylic-acid-in-bone-tissue-scaffolds(0f3b96dd-29e6-4b46-9760-57770dee8bde).html.

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Bone undergoes constant turnover throughout life and has the capacity to regenerate itself. However, the repair of critical size defects, caused by bone diseases such as osteoporosis, can be more problematic. Therefore, there is a clinical need for a bone graft substitute that can be used at sites of surgical intervention to enhance bone regeneration. Poly(vinylphosphonic acid-co-acrylic acid) (PVPA-co-AA) has recently been identified as a potential candidate for use in bone tissue scaffolds. It is hypothesised that PVPA-co-AA can mimic the action of bisphosphonates â a class of drugs used in the treatment of osteoporosis â by binding to calcium ions from bone mineral surfaces. In this way, bisphosphonates can affect bone turnover by increasing the activity of osteoblasts and reducing osteoclast activity. Although PVPA-co-AA has been shown to improve bone formation, the mechanism of action has so far not been fully elucidated. Therefore, this work aims to understand the effect of copolymer composition on the properties of PVPA-co-AA, and thus to determine its effect on osteoblast adhesion and proliferation. PVPA-co-AA copolymers have been synthesised with a range of monomer feed ratios. It was found that a VPA content of 30 mol % led to the greatest calcium binding affinity of the copolymer and is thus expected to lead to enhanced bone formation and mineralisation of the matrix produced by osteoblast cells. The release profile of PVPA-co-AA from electrospun PCL scaffolds was investigated. It was shown that all of the PVPA-co-AA was released into aqueous media within 8 h of immersion. It was also found that the calcium chelation from osteogenic differentiation media significantly increased within the first 8 h. Therefore, it was concluded that PVPA-co-AA is released from the scaffolds, where it can then bind to calcium ions from the bone mineral surface to promote mineralisation, thus acting as a mimic of non-collagenous proteins, which are present in the extracellular matrix (ECM) of bone. Hydrogels of PVPA-co-AA have been produced and the effect of monomer feed ratio (0-50 mol % VPA) on the properties of the gels was explored. It was found that an increase in VPA content led to greater hydrogel swelling and increased porosities. Hydrogels that contained 30 and 50 mol % VPA were shown to have similar morphologies to the native ECM of bone. Rheological testing showed that hydrogels with higher VPA contents were more flexible and could be deformed to a large extent without permanent deformation of their structure. An increase in osteoblast adhesion and proliferation was observed for hydrogels with 30 and 50 mol % VPA content as well as superior cell spreading. Osteoblast cell metabolic activity also increased as a function of VPA content in the hydrogels. This work indicates that hydrogels of PVPA-co-AA, with VPA contents of 30 or 50 mol %, are ideal for use as bone tissue scaffolds. Furthermore, the mechanical and cell adhesion properties of the gels can be tuned by altering the copolymer composition. Finally, composite hydrogels of PVPA-co-AA and hydroxyapatite (HA) have been produced and investigated for their ability to remove fluoride ions from groundwater. It was found that the fluoride uptake ability of PVPA-HA hydrogels was significantly enhanced when compared with HA powder alone. Furthermore, the fluoride uptake was dependent on many factors, including pH, contact time and the presence of competing ions. It was possible to regenerate the hydrogel to remove the fluoride ions, and thus it was shown that the material can be used a number of times with only a slight reduction in its fluoride uptake capacity.

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Takahashi, Yoshitake. "MATERIAL DESIGN OF BIODEGRADABLE CELL SCAFFOLDS FOR CONTROLLED RELEASE OF BONE MORPHOGENETIC PROTEIN-2 AND THE BONE REGENERATION POTENTIAL." Doctoral thesis, 京都大学 (Kyoto University), 2007. http://hdl.handle.net/2433/44145.

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学位授与年月日: 2007-07-23 ; 学位の種類: 新制・論文博士 ; 学位記番号: 論工博第3968号
GENERAL INTRODUCTION: Bone reconstruction is a clinically important procedure to treat bone defects and has been widely tried by different methods. Basically, bone has the inherent ability to spontaneously repair itself for the bone fracture of small size. However, such a self-repairing cannot always be expected for large-size defects that are caused by trauma, tumor resection, spinal arthodesis, and congenital abnormalities. This situation often happens clinically and the therapeutic demand has been being increased recently [1]. Autograft, which is considered to be a gold standard as bone substitutes, is applied to the defect site because it provides a suitable environment for cell attachment, proliferation, and differentiation for bone regeneration [2]. However, it has several disadvantages, such as the limited donor supply, potential complications with chronic pain at the donor sites [3, 4]. On the other hand, allograft is being performed clinically [2], but the rate of graft integration into the surrounding natural bone is lower than that of autograft. In addition, it is necessary for the allograft to consider a risk of disease transmission and postoperative complications due to the tissue rejection [4, 5]. Therefore, under these circumstances, as the substitute for the bone grafts, the biomaterials of metals and ceramics have been investigated and developed. Although the above problems may be cleared, they have other disadvantages, such as the lack of biodegradability under physiological conditions and the limited processability [6]. Especially, metals show poor integration property to the bone tissue at the implantation site compared with the autograft and allograft although they provide mechanical support [7]. Different from artificial biomaterials, one of the important advantages for the bone graft is to positively accelerate osteoconduction and osteoinduction. As one trial to tackle and improve the points to be resolved, bone tissue engineering has been attracted much attention as a new therapeutic technology [8-11]. The basic idea is to provide key cells the local environment suitable to promote their proliferation and differentiation for the induction of tissue regeneration. (...)　In summary, this thesis describes the feasibility of gelatin-based scaffolds in the controlled release carrier of BMP-2 and the three-dimensional matrix of MSC for osteogenic differentiation. It is concluded that this material design of scaffold is promising to effectively induce bone regeneration based on tissue engineering.
京都大学
0048
新制・論文博士
博士(工学)
乙第12103号
論工博第3968号
新制||工||1418(附属図書館)
UT51-2007-M983
(主査)教授田畑泰彦, 教授岩田博夫, 教授木村俊作
学位規則第4条第2項該当
Doctor of Engineering
Kyoto University
DFAM

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15

Schäfer, Gesa [Verfasser]. "Development of helix-mimetic scaffolds as potential disruptors of the interaction between protein kinase A and A kinase anchoring proteins / Gesa Schäfer." Berlin : Freie Universität Berlin, 2012. http://d-nb.info/1029937028/34.

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16

Liang, Meng. "Spatial organization of electric charges and discharge kinetics of nanofibers elaborated by electrospinning : application to the elaboration of 3D structured nanofibrous materials." Thesis, Strasbourg, 2020. http://www.theses.fr/2020STRAE002.

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L’electrospinning est un procédé permettant la production de matériaux nanofibreux sous l'action d'un champ électrostatique intense. Au cours du procédé, une solution de polymère en régime semi-dilué enchevêtré est introduite dans une aiguille métallique soumise à un potentiel électrique élevé. Lorsque le champ électrique entre l'aiguille et une contre-électrode métallique reliée à la terre électrique, appelée collecteur, est suffisamment fort (de l’ordre de 1 kV/cm), un jet de la solution est violemment éjecté vers le collecteur. Pendant le vol entre l'aiguille et le collecteur, le jet est soumis à des instabilités électro-hydrodynamiques qui provoquent des mouvements de fouet favorisant l'évaporation du solvant et la réduction du diamètre. Après un temps de vol de quelques ms, une nanofibre polymère solide est déposée sur le collecteur sous la forme d’un scaffold non-tissé. Lorsque la nanofibre chargée électriquement est mise en contact avec le collecteur, elle se décharge progressivement. La cinétique de la décharge électrique mais aussi la façon dont les charges sont réparties à la surface du matériau pendant le procédé déterminent l'organisation et la structuration 3D finale du scaffold.Les travaux de cette thèse ont consisté à mesurer les charges électriques portées par la nanofibre lors de son dépôt mais aussi à étudier comment ces charges se dissipent dans la membrane et dans le temps, une fois la nanofibre déposée. Cette étude a ensuite été appliquée au développement de scaffolds nanofibreux de structure contrôlée en 3D
Electrospinning is a process allowing the production of nanofibrous materials under the action of an intense electrostatic field. During the process, a polymer solution in a semi-diluted entangled regime is fed to a metal needle submitted to a high electrical potential. When the electric field between the needle and a metal counter electrode connected to the electrical ground, called a collector, is strong enough (i.e. about 1 kV/cm), a jet of the solution is violently ejected towards the collector. During the flight between the needle and the collector, the jet is subjected to electro-hydro-dynamic instabilities resulting in whipping movements that promote solvent evaporation and diameter reduction. After a flight time of a few ms, a solid polymer nanofiber in the form of a non-woven membrane is deposited on the collector. When the electrically charged nanofibre is brought into contact with the collector, it gradually discharges. The kinetics of electrical discharge but also the way in which the charges are distributed on the surface of the material during the process determine the organization and the final 3D structuring of the membrane.The work of this thesis consisted in measuring the electrical charges carried by the nanofibre during its deposition but also in studying how these charges dissipate in the membrane and over time once the nanofibre has been deposited. This study was then applied to develop nanofiber membranes with a controlled 3D structure

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17

Huang, Yijiang [Verfasser], and Peter [Akademischer Betreuer] Müller. "Chondrogenic differentiation and proliferation potential of human adipose-derived stem cells combined porous chitosan-based scaffolds for articular cartilage formation in vitro / Yijiang Huang ; Betreuer: Peter Müller." München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2019. http://d-nb.info/1182228720/34.

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18

Kim, Margaret. "Comparison of ovine mesenchymal cell and osteoblast osteogeic capacity in 2D and 3D." Thesis, Queensland University of Technology, 2014. https://eprints.qut.edu.au/75765/1/Margaret_Kim_Thesis.pdf.

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This thesis explored the different bone-forming potential of specific bone cells with differing embryological origin, on conventional culture platforms compared to 3D biocompatible scaffolds in vitro. Bone mesenchymal stem cells, mandibular osteoblasts and long bone osteoblasts from adult and juvenile sheep were compared in the study, as the embryological origin of the osteoblasts from the craniofacial and appendicular skeleton differs. The study demonstrated differing characteristics of the various cell types when cultured on the two different platforms compared and this may have an impact on future research into cell seeded tissue scaffolds to aid in vivo tissue regeneration.

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Orkun, Cevheroglu. "Unexpected Cyclization Of Dipyrilydl-glycoluril In The Presence Of Formaldehyde And Strong Acid: A New Scaffold With A Potential As A Receptor And Synthesis Of Vairous Calixarene Precursors." Master's thesis, METU, 2005. http://etd.lib.metu.edu.tr/upload/12606423/index.pdf.

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This thesis covers combination of two independent works accomplished throughout the study. One part research is about the unexpected cyclization of Dipyridyl-glycoluril, and the other part is about synthesis of precursor calix[4]arene derivatives. In an attempted synthesis of peripherally pyridine substituted cucurbituril, an unexpected cyclized product was obtained. A careful NMR analysis followed by mass spectrometry and preliminary crystallographic analyses, helped us in resolving the structure. The structure has two quaternized pyridine functionalities and a groove suitable as a potential receptor site. In addition, just like the parent glycoluril structure, two remaining urea-derived nitrogens can be alkylated by alkyl halides. Thus, we believe this high yielding reaction may become an entry point to a new class of anion receptors. In the second work, certain important calix[4]arene derivatives were synthesized. They are the building blocks of important potential molecular, anion and cation sensing, and enzyme mimics. For these precursor molecules, functionalizations both on lower and upper rim have been studied. A careful study on NMR data has been performed and detailed investigation on the NMR data was discussed herein. Applying further one or two step procedures produces important target molecules having potential as sensors or artificial enzymes.

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Southworth, Adam R. "Potential commercialization of a collagen-GAG scaffold for liver regeneration." Thesis, Massachusetts Institute of Technology, 2008. http://hdl.handle.net/1721.1/45354.

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Thesis (M. Eng.)--Massachusetts Institute of Technology, Dept. of Materials Science and Engineering, 2008.
Includes bibliographical references (p. 63-65).
The potential for commercializing a scaffold made of collagen and glycosaminoglycan to help regenerate cirrhotic liver was analyzed and a business plan and model were created. Using a lypholization technique, a bulk-sized and highly porous scaffold is created. It is then inserted into the hole created by the excised liver scar tissue. By blocking contraction of the wound and mimicking the natural extracellular matrix, the scaffold induces regeneration of normal liver tissue. The in vivo approach is compared to several other experimental treatments of cirrhosis found in the literature. The difficulties that need to be addressed are explained and potential solutions are given. A cost model was created, incorporating equipment, labor, FDA, and raw material costs. This model was combined with information regarding the cost of current liver transplant procedures to create a profitable business plan based on the collagen-GAG scaffolds. A manufacturing and product sales business model was chosen due to the fairly low level of market competition and moderate barrier to entry. The intellectual property landscape is described and analyzed in terms of problematic existing patents and the potential for protecting the proposed scaffolds. A timeline for future research and development was created, with potential sources of funding during each phase. In addition to the current embodiment of the scaffold, possible changes to the scaffold properties and composition are proposed.
by Adam R. Southworth.
M.Eng.

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21

Simkovsky, Nadja Melitta. "Synthesis of some potential IKK inhibitors based around a pyrimidine scaffold." Thesis, University of Liverpool, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.367619.

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22

Hakimi, Osnat. "Silkworm and spider silks as potential scaffold materials for tissue engineering." Thesis, Queen Mary, University of London, 2008. http://qmro.qmul.ac.uk/xmlui/handle/123456789/506.

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Silks have been described as biocompatible materials with a range of excellent mechanical properties, particularly a rare combination of strength and elasticity thought to arise from their unique molecular composition and ultrastructure. This project was aimed at studying the potential of natural silk fibres for tissue engineering. Species studied included degummed brins from the domestic silkworm Bombyx mori, the wild silkworm Antheraea pernyi and egg sac silk fibres from the spider Nephila edulis. A qualitative and quantitative description of the physical properties of the silks was carried out, where surface appearance, morphology and ultrastructure were investigated using a variety of microscopy techniques. The intrinsic fluorescence, density, linear density and cross section of silk fibres were also measured, facilitating a numerical estimation of their surface area per unit weight. Consequently, the tensile properties of the silks were measured, prior to and post cell culture preparation. The effect of autoclaving, washing and storage in growth medium was assessed through different tensile parameters. Upon culturing endothelial cells on the silk, a marked toxic effect was recorded and investigated, and different washing procedures to remove the toxic effect have been tested. Cell adhesion studies compared the ability of the different silks to support cell attachment for up to ten days. Also measured was as the effect of different treatments of the silk and scaffold design on rates of cell attachment. Finally, a new method of surface modification was developed and tested in order to functionalise natural silk fibres for endothelial guidance and angiogenesis. Results showed that all three silks shared a similar hierarchical ultrastructure of nanofibrils bundled into microfibrils, running parallel to the axis of the fibre. The silks also shared a lined, ridged topography where the fibroin monofilament was exposed or smooth topography when still coated in gum. However, tested silks differed in diameter, morphology, amino acid content and intrinsic fluorescence. Tensile tests showed that preparation for cell culture procedures, including sterilisation by autoclaving and water wetting had little or no effect on the mechanical properties, with the exception of medium incubation, which had a statistically significant effect on the mechanical properties of all tested silks. Cell growth studies showed that exposure of endothelial and myofibroblast cells to silk reduced their growth rates. The effect was mediated by iii both direct and indirect exposure to all tested silks, but most markedly by A. pernyi, which caused a severe cytostatic effect. One study showed that incubation of A.pernyi silk in medium supplemented with serum (but not non-supplemented medium) resulted in highly toxic growth medium. Among the different washing procedures devised to remove the toxicity, only lengthy enzymatic degumming was effective in reducing the toxic effect. Cell adhesion and growth studies indicated endothelial cells could attach and grow on the silk, but adhesion improved after the enzyme treatment. Scaffold design was also shown to have some effect on adhesion, with three-dimensional woven fabric proving a better scaffold than a random mesh of fibres. Finally, it was reported that the transglutaminase Factor XIII might be used to modify the surface of silk fibres with the biologically active factor L1Ig6. To conclude, studies presented in this described two poorly characterised silk species (Antheraea pernyi cocoon and Nephila edulis egg case) in term of their morphology, ultrastructure and fluorescence. They then showed that native, nonmodified silks supported cell attachment and growth provided they were treated to remove toxic coating and used in the form of a woven fabric rather then a loose mesh of fibres. Studies also presented a quantitative approach to the utilisation of silk in tissue engineering, and established wild silkworm silk Antheraea as a superior scaffold compared with egg case from the spider Nephile edulis or the domestic silkworm Bombyx mori. Finally, the novel method of silk modification using Factor XIII was reported as a potential route to further enhancing native silk fibres as cell scaffolds for specific applications. These studies present a unique approach, as they intentionally avoided harsh modifications of silk fibres before their use as scaffolds in order to preserve their excellent mechanical properties.

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Gaut, Ludovic. "Mechanical and molecular signals underlying tendon cell differentiation." Electronic Thesis or Diss., Sorbonne université, 2018. http://www.theses.fr/2018SORUS301.

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Les tendons sont une forme unique de tissu conjonctif au sein du système musculosquelettique. Le développement, l’homéostasie et la réparation du tendon reposent sur des combinaisons de paramètres moléculaires et aussi mécaniques, régulant la production et l’assemblage des fibres de collagène. Notre objectif est de comprendre quelles sont les voies de mécanotransduction impliquées dans la différentiation tendineuse, via deux (co-)facteurs de transcription : EGR1 et YAP. Nous avons montré que l’expression du gène de tendon SCX, de EGR1 et l'activité de YAP sont réduites dans les tendons de membres de fœtus de poulet immobilisés. De plus, la reprise des contractions musculaires entraîne une reprise de l’expression des gènes de tendon comparable à celle des fœtus jamais immobilisés. La mécanobiologie du tendon a été étudiée avec des constructions cellulaires en 3-dimensions (3D) en gel de fibrine ou de collagène, faits de cellules souches mésenchymateuses. La perte de tension de ces constructions a induit une chute de l’expression de Egr1, des gènes de tendon et de l’activité de YAP. Une surexpression de Egr1 dans les constructions 3D en gel de fibrine sans tension a empêché la chute d’expression des gènes de tendon. L’activité de YAP et l’expression de Scx ont augmenté en étirant les constructions en gel de collagène. L’inactivation de l’activité de YAP par traitement à la verteporfin (VTPF) a induit une diminution de l’expression des gènes de tendon, qui n’a pas été restaurée lorsque ces constructions traitées ont été étirées. Ensemble, ces résultats montrent l’importance de YAP et EGR1 en aval des signaux mécaniques pour réguler la différentiation des cellules du tendon
Tendons are unique forms of connective tissue of the musculoskeletal system. Tendon development, homeostasis and repair rely on specific combinations of mechanical and molecular factors regulating the production and assembly of collagen fibers. Our objective is to decipher the mechanotransduction pathways underlying tendon cell differentiation, through the activity of two transcription (co-)factors, EGR1 and YAP. We showed that the expression of the tendon gene SCX, the mechanosensitive gene EGR1 and YAP activity were downregulated in limb tendons of immobilized chicken fetuses. Restored muscle contraction after immobilization led to a recovery of tendon gene expression. Tendon mechanobiology was studied in vitro in fibrin- or collagen-based 3-dimensional (3D) constructs made of mesenchymal stem cells and mimicking tendon formation. Tension release in fibrin and collagen 3D-constructs induced a drop of the expression of Egr1, tendon genes and YAP activity. Overexpression of Egr1 was able to prevent the downregulation of tendon gene expression in de-tensioned fibrin 3D-constructs. YAP activity was upregulated in dynamically stretched collagen 3D-constructs and was paired with the expression of the tendon gene Scx. Chemical knock-down of YAP activity with Verteporfin (VTPF) treatment showed a decrease in the expression of YAP target genes and the tendon genes. Besides, dynamic stretch applied on VTPF-treated constructs did not restore tendon gene expression, conforting the role of YAP as an intracellular relay of mechanical cues in tendon cells. Altogether, these results highlight the importance of EGR1 and YAP downstream of mechanical forces during tendon cell differentiation

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Egieyeh, Samuel Ayodele. "Computational strategies to identify, prioritize and design potential antimalarial agents from natural products." University of the Western Cape, 2015. http://hdl.handle.net/11394/5058.

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Philosophiae Doctor - PhD
Introduction: There is an exigent need to develop novel antimalarial drugs in view of the mounting disease burden and emergent resistance to the presently used drugs against the malarial parasites. A large amount of natural products, especially those used in ethnomedicine for malaria, have shown varying in-vitro antiplasmodial activities. Facilitating antimalarial drug development from this wealth of natural products is an imperative and laudable mission to pursue. However, the limited resources, high cost, low prospect and the high cost of failure during preclinical and clinical studies might militate against pursue of this mission. Chemoinformatics techniques can simulate and predict essential molecular properties required to characterize compounds thus eliminating the cost of equipment and reagents to conduct essential preclinical studies, especially on compounds that may fail during drug development. Therefore, applying chemoinformatics techniques on natural products with in-vitro antiplasmodial activities may facilitate identification and prioritization of these natural products with potential for novel mechanism of action, desirable pharmacokinetics and high likelihood for development into antimalarial drugs. In addition, unique structural features mined from these natural products may be templates to design new potential antimalarial compounds. Method: Four chemoinformatics techniques were applied on a collection of selected natural products with in-vitro antiplasmodial activity (NAA) and currently registered antimalarial drugs (CRAD): molecular property profiling, molecular scaffold analysis, machine learning and design of a virtual compound library. Molecular property profiling included computation of key molecular descriptors, physicochemical properties, molecular similarity analysis, estimation of drug-likeness, in-silico pharmacokinetic profiling and exploration of structure-activity landscape. Analysis of variance was used to assess statistical significant differences in these parameters between NAA and CRAD. Next, molecular scaffold exploration and diversity analyses were performed on three datasets (NAA, CRAD and malarial data from Medicines for Malarial Ventures (MMV)) using scaffold counts and cumulative scaffold frequency plots. Scaffolds from the NAA were compared to those from CRAD and MMV. A Scaffold Tree was also generated for all the datasets. Thirdly, machine learning approaches were used to build four regression and four classifier models from bioactivity data of NAA using molecular descriptors and molecular fingerprints. Models were built and refined by leave-one-out cross-validation and evaluated with an independent test dataset. Applicability domain (AD), which defines the limit of reliable predictability by the models, was estimated from the training dataset and validated with the test dataset. Possible chemical features associated with reported antimalarial activities of the compounds were also extracted. Lastly, virtual compound libraries were generated with the unique molecular scaffolds identified from the NAA. The virtual compounds generated were characterized by evaluating selected molecular descriptors, toxicity profile, structural diversity from CRAD and prediction of antiplasmodial activity. Results: From the molecular property profiling, a total of 1040 natural products were selected and a total of 13 molecular descriptors were analyzed. Significant differences were observed between the natural products with in-vitro antiplasmodial activities (NAA) and currently registered antimalarial drugs (CRAD) for at least 11 of the molecular descriptors. Molecular similarity and chemical space analysis identified NAA that were structurally diverse from CRAD. Over 50% of NAA with desirable drug-like properties were identified. However, nearly 70% of NAA were identified as potentially "promiscuous" compounds. Structure-activity landscape analysis highlighted compound pairs that formed "activity cliffs". In all, prioritization strategies for the natural products with in-vitro antiplasmodial activities were proposed. The scaffold exploration and analysis results revealed that CRAD exhibited greater scaffold diversity, followed by NAA and MMV respectively. Unique scaffolds that were not contained in any other compounds in the CRAD datasets were identified in NAA. The Scaffold Tree showed the preponderance of ring systems in NAA and identified virtual scaffolds, which maybe potential bioactive compounds or elucidate the NAA possible synthetic routes. From the machine learning study, the regression and classifier models that were most suitable for NAA were identified as model tree M5P (correlation coefficient = 0.84) and Sequential Minimization Optimization (accuracy = 73.46%) respectively. The test dataset fitted into the applicability domain (AD) defined by the training dataset. The “amine” group was observed to be essential for antimalarial activity in both NAA and MMV dataset but hydroxyl and carbonyl groups may also be relevant in the NAA dataset. The results of the characterization of the virtual compound library showed significant difference (p value < 0.05) between the virtual compound library and currently registered antimalarial drugs in some molecular descriptors (molecular weight, log partition coefficient, hydrogen bond donors and acceptors, polar surface area, shape index, chiral centres, and synthetic feasibility). Tumorigenic and mutagenic substructures were not observed in a large proportion (> 90%) of the virtual compound library. The virtual compound libraries showed sufficient diversity in structures and majority were structurally diverse from currently registered antimalarial drugs. Finally, up to 70% of the virtual compounds were predicted as active antiplasmodial agents. Conclusions:Molecular property profiling of natural products with in-vitro antiplasmodial activities (NAA) and currently registered antimalarial drugs (CRAD) produced a wealth of information that may guide decisions and facilitate antimalarial drug development from natural products and led to a prioritized list of natural products with in-vitro antiplasmodial activities. Molecular scaffold analysis identified unique scaffolds and virtual scaffolds from NAA that possess desirable drug-like properties, which make them ideal starting points for molecular antimalarial drug design. The machine learning study built, evaluated and identified amply accurate regression and classifier accurate models that were used for virtual screening of natural compound libraries to mine possible antimalarial compounds without the expense of bioactivity assays. Finally, a good amount of the virtual compounds generated were structurally diverse from currently registered antimalarial drugs and potentially active antiplasmodial agents. Filtering and optimization may lead to a collection of virtual compounds with unique chemotypes that may be synthesized and added to screening deck against Plasmodium.

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25

Puig, Sanvicens Verònica. "Cardiomyogenic potentiality of somatic and stem cells when cultured in the three-dimensional peptide scaffold RAD16-I." Doctoral thesis, Universitat Ramon Llull, 2014. http://hdl.handle.net/10803/128947.

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Les malalties cardiovasculars són una de les majors causes de mortalitat a escala mundial. L’infart de miocardi és el principal responsable de les cardiopaties isquèmiques. La irrigació sanguínia al cor es veu bloquejada degut a una oclusió en un capil•lar sanguini provocant mort cel•lular massiva que genera una zona miocardíaca necròtica. En la última dècada, la medicina cardíaca regenerativa s’ha focalitzat en estratègies fonamentades en l’enginyeria de teixits i la teràpia cel•lular basada en cèl•lules mare. En aquest treball, hem caracteritzat el potencial cardíac de diferents tipus cel•lulars cultivats en bastides tri-dimensionals (3D) generades a partir de l’hidrogel peptídic RAD16-I. En primer lloc, hem estudiat l’adquisició de potencial mesenquimàtic de fibroblasts humans de dermis (hNDFs) en cultius 3D i la seva diferenciació subseqüent a llinatges adipogènic i cardiogènic. Únicament els hNDFs cultivats en hidrogels de RAD16-I adquireixen una potenciació mesenquimàtica. Les cèl•lules adopten espontàniament propietats semblants a les cèl•lules mare mesenquimàtiques mentre que la diferenciació a adipogènesis i cardiogènesis requereix medi d’inducció. En segon lloc, hem comparat el grau de diferenciació cardíaca de cèl•lules mare humanes pluripotents induïdes (hiPSCs) cultivades en ambients 2D versus 3D i hem avaluat l’efecte de l’àcid ascòrbic (AA) en el procés. En el nostre treball i com ja s’havia demostrat en publicacions prèvies, l’AA va resultar accelerar i millorar la diferenciació cardíaca de hiPSCs en cultius 2D. A més, els resultats presentats suggereixen que les hiPSCs cultivades en 3D augmenten el seu grau de diferenciació i adquireixen un potencial cardiogènic 105 vegades més elevat que en els cultius 2D. En tercer lloc, hem dissenyat un pegat cardíac basat en cultius 3D de cèl•lules adultes porcines progenitores del teixit adipós del mediastí (pMATPCs) injectats en matrius naturals (pericardi humà descel•lularitzat). Hem implantat la bio-pròtesis miocardíaca in vivo i hem determinat que la bio-bastida afavoreix la migració cel•lular i la regeneració de la zona infartada en el model porcí. En conclusió, hem analitzat el potencial cardiogènic de cèl•lules adultes somàtiques (hNDFs), cèl•lules mare adultes (pMATPCs) i cèl•lules mare pluripotents (hiPSCs) en cultius 3D basats en hidrogels de RAD16-I per a futures aplicacions en el tractament de malalties cardíaques.
Las enfermedades cardiovasculares son una de las mayores causas de mortalidad a escala mundial. El infarto de miocardio es el principal responsable de las cardiopatías isquémicas. La irrigación sanguínea al corazón se ve bloqueada debido a una oclusión en un capilar sanguíneo provocando muerte celular masiva que genera una zona miocárdica necrótica. En la última década, la medicina cardíaca regenerativa se ha focalizado en estrategias fundamentadas en la ingeniería de tejidos y la terapia celular basada en células madre. Es este trabajo, hemos caracterizado el potencial cardíaco de distintos tipos celulares cultivados en andamios tridimensionales (3D) generados a partir del hidrogel peptídico RAD16-I. En primer lugar, hemos estudiado la adquisición de potencial mesenquimático de fibroblastos humanos de dermis (hNDFs) en cultivos 3D y su diferenciación subsecuente a linajes adipogénico y cardiogénico. Únicamente los hNDFs cultivados en hidrogeles de RAD16-I adquieren una potenciación mesenquimática. Las células adoptan espontáneamente propiedades parecidas a las células madre mesenquimáticas mientras que la diferenciación a adipogénesis y cardiogénesis requiere medio de inducción. En segundo lugar, hemos comparado el grado de diferenciación cardíaca de células madre humanas pluripotentes inducidas (hiPSCs) cultivadas en ambientes 2D versus 3D y hemos evaluado el efecto del ácido ascórbico (AA) en el proceso. En nuestro trabajo y como ya se había demostrado en publicaciones previas, el AA resultó acelerar y mejorar la diferenciación cardíaca de hiPSCs en cultivos 2D. A demás, los resultados presentados sugieren que las hiPSCs cultivadas en 3D aumentan su grado de diferenciación y adquieren un potencial cardiogénico 105 veces más elevado que en los cultivos 2D. En tercer lugar, hemos diseñado un parche cardíaco basado en cultivos 3D de células adultas porcinas progenitoras del tejido adiposo del mediastino (pMATPCs) inyectados en matrices naturales (pericardio humano descelularizado). Hemos implantado la bio-prótesis miocárdica in vivo y hemos determinado que el bio-andamio favorece la migración celular y la regeneración de la zona infartada en el modelo porcino. En conclusión, hemos analizado el potencial cardiogénico de células adultas somáticas (hNDFs), células madre adultas (pMATPCs) y células madre pluripotentes (hiPSCs) en cultivos 3D basados en hidrogeles de RAD16-I para futuras aplicaciones en el tratamiento de enfermedades cardíacas.
Cardiac failure is the primary cause of mortality throughout the world. One of the leading causes of heart failure is myocardial infarction, which results from a reduced flow of blood to a part of the heart. This leads to cardiomyocyte death and myocardial necrosis. In the past decade, various strategies for cardiac reparative medicine have been investigated, from tissue engineering to stem cell-based therapy. Herein, we characterized the cardiac potential of different cell types cultured in three-dimensional (3D) scaffolds based on the peptide hydrogel RAD16-I. Firstly, we studied the mesenchymal potential acquisition of human Normal Dermal Fibroblasts (hNDFs) in 3D cultures and further commitment into adipogenic and cardiogenic lineages. We suggest that only hNDFs cultured in RAD16-I hydrogels undergo a mesenchymal potentiation. Cells spontaneously acquired mesenchymal stem cell-like properties whereas they required induction media to differentiate into adipogenic- and cardiogenic-like lineages. Secondly, we compared the degree of cardiac commitment of human induced Pluripotent Stem Cells (hiPSCs) when cultured in 2D versus 3D and the effect of ascorbic acid (AA), which has been proven to promote cardiac differentiation, on the process. In fact, AA seemed to accelerate and improve the cardiac commitment of hiPSCs in 2D cultures. Results suggested that hiPSCs in 3D cultures displayed an increased level of differentiation and acquired 105-fold more cardiogenic potential than cells cultured in 2D. Thirdly, we designed a cardiac patch based on 3D cultures of adult porcine Mediastinal Adipose Tissue Progenitor Cells (pMATPCs) injected into natural matrices (decellularized human pericardium). We implanted the myocardial bioprosthesis in vivo and determined that the bioscaffold supported cell migration and regeneration into the infarcted area in swine. In summary, we studied the cardiogenic potential of adult somatic cells (hNDFs), adult stem cells (pMATPCs) and pluripotent stem cells (hiPSCs) in 3D cultures based on RAD16-I hydrogels for potential future applications in the treatment of heart disease.

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Ramirez, Magaly Alexandra. "Cellulose Nanocrystals Reinforced Electrospun Poly(lactic acid) Fibers as Potential Scaffold for Bone Tissure Engineering." NCSU, 2010. http://www.lib.ncsu.edu/theses/available/etd-04012010-153822/.

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Poly(lactic acid) / Cellulose Nanocrystals (PLA / CNs) were simultaneously electrospun to fabricate a novel renewable and biocompatible nanocomposite as potential scaffold for bone tissue engineering. CNs were successfully incorporated into the PLA fibers to reinforce the electrospun fiber mat. Thermal, chemical and mechanical analyses were performed to characterize and determine the properties of the scaffold fabricated. Highly porous fibers with fibers diameters in the range of 500-1000 nm were characterized by Scanning Electron Microscopy (SEM) and Transmission Electron Microscopy (TEM). Crystallinity of the electrospun nanocomposite was studied by Differential Scanning Calorimetry. Adipose-derived human mesenchymal stem cells (hMSCs) were used to study the cytocompatibility of the nanocomposite scaffold. Life/dead cell assay was performed to determine cell viability of the scaffolds. After one week of cell culture, confocal microscopy indicated that the cells grown on the PLA / CNs nanocomposite were confluent and very well aligned along the fibers while cells cultured on pure PLA fibers were not as confluent as in the developed nanocomposite. This project has demonstrated the feasibility of the fabricated PLA/CNs nanocomposite as a potential scaffold for bone tissue engineering.

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27

He, Guijia. "Potential inhibitors of COPD-relevant serine proteases based on the N-amino-4-imidazolidinone scaffold." Thesis, Wichita State University, 2009. http://hdl.handle.net/10057/2511.

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Human neutrophil elastase (HNE) and proteinase 3 (PR3) are serine proteases which play a crucial role in the pathogenesis of chronic obstructive pulmonary disease (COPD), a multifactorial disorder associated with an imbalance between the levels of COPD-relevant proteases and their physiological protein inhibitors. The N-amino-4-imidazolidinone scaffold was used in the design and synthesis of potential inhibitors of HNE and PR3. The results show that this is a promising avenue of investigation for the development of reversible competitive inhibitors with good selectivity toward HNE and PR3. Molecular docking simulations are supportive of the validity of this approach.
Thesis (M.S.)--Wichita State University, College of Liberal Arts and Sciences, Dept. of Chemistry

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Cockell, Simon J. "Aplip1, a potential scaffold protein of Drosophila melanogaster, may be involved in facilitating signal transduction." Thesis, University of Leicester, 2004. http://hdl.handle.net/2381/30353.

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The mammalian JIP group of proteins have been shown to have a physiologically important role in controlling the specificity of JNK signal transduction. The Drosophila gene SP512 has been identified as a homologue of JIP1 and JIP2, and is termed aplip1. Expression studies of the aplip1 gene reveal that it is expressed in the embryonic nervous system, the eye imaginal disc, and the nurse cells of the developing oocyte. In an attempt to generate an alpha-Aplip1 antibody, 6xHIS-tagged Aplip1 protein was expressed in E. coli and purified on a Ni2+-NTA column. The resulting purified Aplip1 protein used to generate an antibody that bound to the protein in vitro but did not when the protein was present in physiological levels. To investigate the function of aplip1 in Drosophila the protein was used in the yeast two-hybrid assay to show that it could interact with the products of the basket, rolled, jun-related antigen, and kinesin light chain genes. Partial deletions of the Aplip1 protein were used to refine the areas of the protein with which these partners could interact, showing that they all interact with the N-terminal region. Finally RNA interference was used to reduce the levels of aplip1, although no mutant phenotype could be detected.

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Lohneis, Taylor Paige. "Consistent Fabrication of Ultrasmall PLGA Nanoparticles and their Potential Biomedical Applications." Thesis, Virginia Tech, 2019. http://hdl.handle.net/10919/95943.

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Nanotechnology and its potential for biomedical applications has become an area of increasing interest over the last few decades. Specifically, ultrasmall nanoparticles, ranging in size from 5 to 50 nm, are highly sought after for their physical and chemical properties and their ability to be easily transmitted though the bloodstream. By adjusting the material properties, size, surface potential, morphology, surface modifications, and more, of nanoparticles, it is possible to tailor them to a specific use in biomedical areas such as drug and gene delivery, biodetection of pathogens or proteins, and tissue engineering. The aim of this study was to fabricate ultrasmall poly-(lactic-co-glycolic acid) nanoparticles (PLGA NPs) using a quick and easy nanoprecipitation method1, with some modifications, for general use in various biomedical areas. Nanoprecipitation of two solutions – PLGA dissolved in acetonitrile and aqueous poly(vinyl alcohol) (PVA) – at varying concentrations produced ultrasmall nanoparticles that range in size, on average, from 10 to 30 nm. By the data collected from this study, a selection method can be used to choose a desired PLGA nanoparticle size given a potential biomedical application. The desired nanoparticle can be fabricated using specific concentrations of the two nanoprecipitation solutions. Size of the ultrasmall PLGA NPs was characterized by dynamic light scattering (DLS) and confirmed by transmission electron microscopy (TEM). Spherical morphology of the PLGA NPs was also proved by TEM. By generalizing the ultrasmall PLGA NP fabrication process, the idea is that these NPs will be able to be used in various biomedical applications depending on the goal of the furthered study. As an example of potential application, ~15 to 20 nm PLGA NPs were consistently fabricated for use as virus-like particle (VLP) scaffolds. Following formation, PLGA NPs were introduced to modified human papillomavirus (HPV) protein during protein refolding and assembly into virus-like particles (VLPs) via buffer exchange. The size of the VLPs was monitored with and without PLGA nanoparticles present in solution during the refolding process and TEM images were collected to confirm encapsulation.
Master of Science
Nanotechnology, the manipulation of materials on an atomic or molecular scale, and its potential for biomedical applications has become an area of increasing interest over the last few decades. Nanoparticles, spherical or non-spherical entities of sizes approximately one-billionth of a meter, have been used to solve a wide variety of biomedical problems. For reference, a human hair is about 80,000 to 100,000 nm in size and the nanoscale typically ranges in size from 1 to 1000 nm. This size range is not visible to the naked eye, so methods of analysis via scientific equipment becomes paramount. Specifically, this study aims to fabricate ultrasmall nanoparticles, ranging in size from 5 to 50 nm, which are highly sought after for their physical and chemical properties and their ability to easily travel though the bloodstream. By adjusting the material properties, size, shape, surface charge, surface modifications, and more, of nanoparticles, it is possible to tailor them to a specific use in biomedical areas such as drug delivery, detection of viruses, and tissue engineering. The specific aim of this study was to fabricate ultrasmall poly-(lactic-co-glycolic acid) nanoparticles (PLGA NPs), a type of polymer, using a quick and easy nanoprecipitation method1, with some modifications. Nanoprecipitation occurs by combining two liquid solutions – PLGA and aqueous poly(vinyl alcohol) (PVA) – which interact chemically to form a solid component – a polymer nanoparticle. These two solutions, at varying concentrations, produced ultrasmall nanoparticles that range in size, on average, from 10 to 30 nm. Data collected from this study can be used to select a desired nanoparticle size given a potential application. The desired nanoparticle can be fabricated using specific concentrations of the two nanoprecipitation solutions. By generalizing the ultrasmall PLGA NP fabrication process, the idea is that these NPs can be used for a variety of biomedical applications depending on the goal of the furthered study. Two PLGA NP example applications are tested for in this work – in DNA loading and in encapsulation of virus-like particles (VLPs), which are synthetically produced proteins that can be neatly folded to resemble a virus. These VLPs can be used to as an alternative to live vaccines and they can be designed to stimulate the immune system. Positive initial results from this study confirm the potential of these nanoparticles to have a wide impact on the biomedical field depending on specific tailoring to a given application.

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Li, Jessica C. (Jessica Ching-Yi). "Potential commercial application of a bi-layer bone-ligament regeneration scaffold to anterior cruciate ligament replacement." Thesis, Massachusetts Institute of Technology, 2006. http://hdl.handle.net/1721.1/37882.

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Thesis (M. Eng.)--Massachusetts Institute of Technology, Dept. of Materials Science and Engineering, 2006.
Includes bibliographical references (p. 71-74).
A business model was created in order to explore the commercial application of a bi-layer bone-ligament scaffold to the treatment of torn anterior cruciate ligaments (ACL) requiring replacement. The two main keys in producing the bone scaffold are triple co-precipitation of type-I collagen, chodroitin-6-sulphate, and calcium phosphate minerals and the use of lyophilization to create a network where all the materials are homogeneously dispersed and present in significant amounts. This process allows the creation of a porous network whose physical characteristics, mechanical properties, and material content can all be changed to create a scaffold that closely mimics natural bone. A collagen and chondroitin-6-sulphate scaffold is used for ligament regeneration. The ACL replacement market was chosen because it is one of the most commonly surgically repaired ligaments in the body and because all of the current treatments have drawbacks.
(cont.) The exercise of creating a business model made it clear that the commercial potential of starting a company that focused on marketing a direct ACL replacement scaffold would most likely not be successful mainly because surgeons would hesitate to use this product over current methods that are satisfactory and it would be difficult to separate our product from other newer methods which all boast similar advantages over current treatment options. However, the commercial potential of using the technology to create a scaffold for graft site morbidity in certain ACL replacement surgeries is large because there is no competition, and the implantation procedure for the surgeon would be simple.
by Jessica C. Li.
M.Eng.

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Mohr, Stefan. "Placenta mesenchymal stem cells on a chorion scaffold as a potential osteogenic graft for peripartal bone regeneration /." [S.l.] : [s.n.], 2008. http://opac.nebis.ch/cgi-bin/showAbstract.pl?sys=000277056.

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Dongargaonkar, Alpana. "SYNTHESIS AND CHARACTERIZATION OF ELECTROSPUN GELATIN/DENDRIMER SCAFFOLD ENCAPSULATED WITH A SILVER AS A POTENTIAL ANTIMICROBIAL WOUND DRESSING." VCU Scholars Compass, 2010. http://scholarscompass.vcu.edu/etd/2318.

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A novel nanofiber scaffold was fabricated and characterized as a potential antimicrobial wound dressing. Half generation polyamidoamine (PAMAM) dendrimer G3.5 was covalently conjugated to gelatin. Gelatin alone or with gelatin-dendrimer conjugates was electrospun into nanofiber scaffolds. Gelatin is a derivative of natural collagen, and it is biocompatible, non-toxic and inexpensive, making it a desirable component in a wound dressing. Dendrimers are synthetic polymers comprising of a central core, internal branches and reactive surface groups. They provide a structurally controlled architecture for drug release. Silver was incorporated into the scaffold in situ due to its broad spectrum of antimicrobial properties. The scaffolds were further crosslinked by photo curable PEG-diacrylate in solution or vapor to gain structure stability. The fabricated scaffolds with various compositions displayed a wide range of structure characteristics and properties in terms of fiber morphology, swelling and degradation, mechanical properties, antimicrobial activity and silver release kinetics. The scaffolds showed a similar fiber structure and morphology. It was found that the fiber diameter of the scaffolds containing silver was greater than scaffolds without silver. The porosity of the crosslinked scaffolds ranged from 67.56% to 90.42% and also exhibited a high capacity of swelling and adsorption. The results of the antimicrobial assay showed that scaffolds containing silver could effectively inhibit growth of bacteria at the end of 48 h. In vitro silver release studies demonstrated that silver could be released in a controlled manner over an extended period of time.

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Nadeem, Muhammad. "Synthesis and characterization of biopolymer nanoapatite composite electrospun bioactive scaffold: A potential application for guided tissue/bone regeneration." University of the Western Cape, 2019. http://hdl.handle.net/11394/7040.

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Philosophiae Doctor - PhD
Search for an ideal scaffold for guided tissue/bone (GTR/GBR) regeneration continues as till now none of the commercially available GTR/GBR membrane fulfils the desired criteria. Currently, a variety of new materials and techniques have been investigated all over the world to improve the properties of GTR/GBR membranes. In the recent past three dimensional bioactive scaffolds composed of natural polymers have gained enormous popularity as potential future GTR/GBR devices. Electrospinning has emerged as one of the relatively simple, cost effective and efficient technique to fabricate three dimensional nanofibrous scaffolds in the field of tissue engineering. The rationale of this project is to investigate the natural polymers based bioactive nanofibrous scaffolds for GTR/GBR applications in the field of Periodontology.

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Tanaka, Kojiro. "A bioactive and bioresorbable porous cubic composite scaffold loaded with bone marrow aspirate: A potential alternative to autogenous bone grafting." Kyoto University, 2010. http://hdl.handle.net/2433/120597.

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Saatchi, Sanaz 1980. "A novel osteochondral composite consisting of a self-assembling peptide hydrogel and 3D printed polycaprolactone scaffold : potential for articular cartilage repair." Thesis, Massachusetts Institute of Technology, 2004. http://hdl.handle.net/1721.1/17949.

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Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Mechanical Engineering, 2004.
Includes bibliographical references (p. 133-135).
Degenerative diseases, such as osteoarthritis, and traumatic injuries are both prominent causes of cartilage defects. Due to its avascular nature, adult human cartilage displays limited capacity for regeneration. Current surgical treatments to induce a spontaneous repair response rely on access to the subchondral bone region. These procedures result in fibrocartilage generation, as opposed to hyaline cartilage, that is variable in structure, composition, and durability. Furthermore, the success rates of these surgeries are also variable. Deficiencies in these cartilage repair methods motivate investigation into a tissue engineering means of repairing or regenerating cartilage. Various composites designed to emulate a cartilage and bone interface are under investigation. The aim of this study was to conceive a means of integrating a chondrocyte-seeded peptide hydrogel with an interconnected porous 3D printed polycaprolactone (PCL) scaffold to create a novel osteochondral construct. The self-assembling peptide hydrogel has been shown to provide an environment that maintains chondrocyte phenotype and viability. Furthermore, the 3D scaffold fosters extracellular matrix production and chondrocyte division. PCL is a bioresorbable and biocompatible polymer scaffold, capable of supporting the attachment of both osteogenic and chondrogenic cells and cell-specific extracellular matrix production, that can be integrated with the peptide hydrogel to constitute an osteochondral construct. A primary advantage of the 3D printing technology is the ability to control the microarchitecture and macroarchitecture of the PCL scaffold in a layer by layer fashion. Integration of the peptide hydrogel into the porous PCL scaffold may be enhanced by creating a gradient of porosity
(cont.) at the interface of the materials, while the lower portion of the PCL scaffold would possess a scaffold microarchitecture optimized for bone ingrowth. Through the use of an agarose mold, the construction of an osteochondral composite consisting of the chondrocyte-seeded peptide hydrogel and porous PCL scaffold was made possible in an integrated, controlled, and repeatable fashion. PCL was found to act as an inert material with regard to chondrocyte behavior, as chondrocyte morphology, viability, extracellular matrix production, and biosynthesis rates proved to be analogous to those seen in the chondrocyte-seeded peptide hydrogel only systems previously studied. A distinction in the microarchitecture of the PCL scaffold, 70% porosity versus 90% porosity, was not found to markedly impact chondrocyte behavior in the peptide hydrogel. The efficacy of the peptide hydrogel material selection was illustrated by comparison to a chondrocyte-seeded agarose hydrogel and PCL composite, with an agarose hydrogel serving as a more traditional means of studying chondrocyte behavior. Biochemical, mechanical, and histological characterization of the peptide hydrogel and porous PCL construct delineate the potential use of this composite for osteochondral defect repair. Future studies may involve dynamic compression of the composite to stimulate extracellular matrix synthesis and accumulation, and in vivo investigations to demonstrate the clinical impacts of such a construct on cartilage repair.
by Sanaz Saatchi.
S.M.

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Sladkova, Martina. "Contributions to the optimisation of the osteogenic Potential of human mesenchymal stem cells seeded on Carbonate calcium scaffold : in vitro and in vivo studies." Paris 7, 2013. http://www.theses.fr/2013PA077043.

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Afin de traiter les grandes pertes de substance osseuse, l'ingenierie tissulaire propose de construire ex vivo des substituts tissulaires ostéogènes composés de cellules souches ensemencées sur un support ostéoconducteur. La présente thèse a été conçue pour mieux comprendre et optimiser le potentiel ostéogene de tels substituts tissulaires. Nous avons tout d'abord étudié l'influence de l'application d'un flux sur la prolifération et la différenciation de cellules souches mesenchymateuses humaines (hcsms) et de progeniteurs mesodermiques issues d'une lignée de cellules souches embryonnaires humaines (hes-mps) ensemencées sur des cubes de corail et cultivées en bioréacteur. Nous avons ensuite évalué le potentiel ostéogene de substituts tissulaires HCSMS/corail cultivés en bioréacteur dans un modèle ectopique murin. A notre grande surprise, ces substituts tissulaires n'étaient pas ostéogenes. Notre hypothèse a été que la taille du support en corail n'était pas optimale pour permettre l'expression du potentiel ostéogène des HCSMS. Cette hypothèse nous a conduits a évaluer l'influence de la taille des particules de corail sur le potentiel ostéogene des HCSMS. Nous avons ainsi pu observer que les potentiels ostéo- et hemato-inducteur des HCSMS était directement dépendant de la taille des particules. De plus, la mort massive des HCSMS apres implantation n'était pas un obstacle à la formation osseuse. Enfin, une analyse détaillée a montre que la distance inter-particulaire ainsi que la resorption du corail étaient des paramètres déterminants des potentiels ostéo- et hemato-inducteur de HCSMS
Tissue engineering (te) aims at obtaining functional tissues by combining cells with a scaffold. Because of their expansion potential, ability to differentiate into various phenotypes, paracrine effects, and immune-modulatory properties, mesenchymal stromal cells (mscs) are a very promising cell type for repairing damaged bone. The efficacy of te in experimental and clinical studies, however, has been less than optimal and remains inferior to that of autologous bone grafts, the gold standard. The present thesis was designed to better understand and optimize the osteogenic potential of such tissue constructs. First, we studied the effect of fluid flow application on the proliferation and differentiation of hmscs and mesodermal progenitors derived from the human embryonic stem cell line (hes-mps) loaded onto coral cubes and cultivated in a bioreactor. Then, we evaluated in an ectopic mouse model the osteogenic potential of hmscs/coral constructs cultured in the bioreactor. Surprisingly, these tissue constructs were not osteogenic. We hypothesized that scaffold size was not optimal for hmscs to express their osteogenic potential. We therefore evaluated the effect of the size of coral particles on the osteogenic potential of hmscs. In this ectopic model, the osteogenic-and hematopoietic-inductive potentials of hmscs were directly dependent on the particle size. Moreover, bone formation was not prevented by massive death of hmscs post-implantation. Last but not least, the detailed histological and micro-ct analysis showed that both the inter-particular distance and coral resorption were critical parameters of the osteogenic-and hematopoietic-inductive potentials of HCSMS

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Collignon, Anne-Margaux. "Utilisation de cellules souches pulpaires combinées à une matrice de collagène pour la réparation osseuse cranio-faciale Strategies developed to induce, direct, and potentiate bone healing Accelerated craniofacial bone regeneration through dense collagen gel scaffolds seeded with dental pulp stem cells Mouse Wnt1-CRE-RosaTomato dental pulp stem cells directly contribute to the calvarial bone regeneration process Early angiogenesis detected by PET imaging with 64Cu-NODAGA-RGD is predictive of bone critical defect repair." Thesis, Sorbonne Paris Cité, 2018. http://www.theses.fr/2018USPCB113.

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La région cranio-faciale est particulièrement vulnérable aux pertes de structures. Sa localisation et sa visibilité font qu'une atteinte entraîne des troubles, aussi bien physiques (alimentation, phonation...) que psychologiques (intégrité de la personne...). Les traitements actuels (régénération osseuse guidée, autogreffe osseuse ou allogreffe) sont particulièrement invasifs et présentent un taux d'échec élevé. Tout cela affecte fortement la qualité de vie du patient. De plus, le coût direct de ces traitements est important pour les systèmes de santé et le patient. Il existe donc un réel besoin de développer des traitements innovants basés sur des approches biomimétiques d'ingénierie tissulaire pour la régénération/réparation osseuse. L'objectif de ce travail est de développer une approche d'ingénierie tissulaire pour la réparation/régénération de tissus osseux cranio-faciaux lésés. Il est basé sur l'utilisation de matrices cellularisées avec des cellules souches mésenchymateuses issues de la pulpe dentaire : les Dental Pulp Stem Cells (DPSCs). De nombreux travaux ont démontré la grande plasticité de ces cellules, qui dérivent initialement de la crête neurale, mais aussi leur rôle trophique dans la réparation de tissus lésés par leur capacité de différenciation ostéogénique et chondrocytaire. Par ailleurs, ces cellules présentent des propriétés pro-angiogéniques supérieures aux cellules mésenchymateuses de la moelle osseuse (MSCs) et l'accès à cette réserve est aisé puisqu'elles peuvent être obtenues à partir de dents extraites. Dans ce contexte, nous avons à ce jour utilisé des matrices denses de collagène contenant des cellules souches pulpaires pour régénérer un tissu osseux crânien après réalisation de défauts critiques. L'objectif est d'induire très précocement une néo-angiogenèse favorisant à court terme la survie des cellules implantées, puis de stimuler leur maintien à long terme au sein du néo-tissu implanté, pour enfin provoquer une ostéoformation. Nous avons, ainsi, pu étudier et valider différents aspects de cette thématique : .1 L'impact positif de l'utilisation de matrices denses de collagène comme support ostéoconducteur, .2 Le suivi à long terme des cellules après implantation in vivo .3 L'impact positif d'un pré-traitement à l'hypoxie sur i/ la survie des cellules après implantation in vivo ii/ la potentialisation de leur apport pour la régénération/réparation osseuse en orientant leur différenciation vers une voie ostéoblastique, .4 L'apport significatif des techniques d'imageries pour le suivi des animaux grâce à la tomographie par émission de positons (utilisation de traceurs spécifiques de la minéralisation au sein des matrices et de la néo-angiogenèse) et au microscanner à rayons X (suivi cinétique de la qualité et de la quantité de matrice osseuse régénérée), .5 La validation et la confirmation de l'ensemble de ces résultats par l'histologie. Ainsi, ces résultats nous ont permis de répondre à l'objectif de travail et de perfectionner certains aspects de la composante cellulaire. Toutefois, il reste nécessaire d'optimiser le biomatériau lui-même. Il est en effet envisageable d'améliorer les matrices de collagène compressées que nous utilisons actuellement, en y intégrant par exemple des céramiques bioactives. En perspective, potentialiser les biomatériaux des matrices et combiner les DPSCs avec un support plus adapté à leur survie et à leur croissance permettrait d'améliorer considérablement la cicatrisation osseuse. Ces dernières années, l'étude des cellules souches a progressé d'approche in vitro vers l'in vivo. Les modèles in vivo établis pour étudier ces cellules dans le domaine cranio-facial ont déjà apporté des renseignements et ce travail s'inscrit dans leur continuité en cherchant à concevoir des stratégies adaptées pour l'utilisation future des DPSCs en ingénierie tissulaire
The craniofacial area is particularly vulnerable to structural loss. Its location and visibility make a loss causes disorders, both physical (food, phonation...) than psychological (integrity of the person...). Current treatments (autografts, allografts or synthetic bone grafts) are particularly invasive and have a high failure rate. All this strongly affects the quality of life of the patient. In addition, the cost of these treatments is significant for the health systems and the patient. Therefore, there is a real need to develop innovative treatments based on biomimetic tissue approaches for bone repair. The purpose of this thesis is to develop a tissue engineering approach for the repair/regeneration of injured cranial-facial bone tissue. It is based on the use of cellularized scaffolds with mesenchymal stem cells derived from the dental pulp: Dental Pulp Stem Cells (DPSCs). Many studies have demonstrated the high plasticity of these cells, which initially derive from the neural crest, but also their trophic ability in the repair of damaged tissues by their osteogenic and chondrocyte differentiation capacity. Moreover, these cells have better's pro-angiogenic properties than mesenchymal cells of the bone marrow (MSCs) and access to this reserve is easy since they can be obtained from extracted teeth. In this context, we have used dense collagen scaffolds seeded with DPSCs to regenerate cranial bone tissue on critical defects model. The objective is to induce a very early neo-angiogenesis for improved short-term survival of implanted cells, then stimulate the long-term maintenance of cells in the implanted neo-tissue, finally to cause osteoformation. We were able to study and validate various aspects of this theme: 1- The positive impact of the use of dense collagen scaffold as osteoconductive support, 2- Long-term follow-up of the cells after implantation in vivo (thanks to the use of a cell line constitutively expressing an intracellular fluorescence protein), 3- The positive impact of a pre-treatment with hypoxia on i/ the survival of the cells after implantation in vivo ii/ their contribution to bone regeneration / repair by orienting their differentiation towards an osteoblastic pathway, 4- The significant contribution of imaging techniques for the monitoring of animals (less sacrifice and longitudinal follow-up...) thanks to positron emission tomography (use of specific tracers of the mineralization within the scaffolds and neo-angiogenesis) and X-ray microscanner (kinetic monitoring of the quality and quantity of regenerated bone matrix) 5- Validation and confirmation of all these results by histology. Thus, these different results allowed us to respond to the working hypothesis and optimize some aspects of the cellular component. However, it remains necessary to optimize the biomaterial itself. It is indeed possible to improve the compressed collagen scaffolds that we currently use, for example by incorporating bioactive ceramics such as bioglasses or hydroxyapatite. In recent years, the study of stem cells has progressed from in vitro to in vivo. The in vivo models established to study these cells in the craniofacial area have already provided valuable information and this work is a continuation of these previous studies by seeking to build on better strategies (right characterization, environment oriented...) for the future use of DPSCs for tissue engineering purposes. In view of this work, potentiating the biomaterials of the scaffolds and combining the DPSCs with a support more adapted to their survival and their growth would considerably improve bone healing, as well as bone regeneration / repair

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CATALANI, MARIA PIA. "Stereoselective synthesis of new piperazinic polycyclic scaffolds with potential biological activity." Doctoral thesis, 2014. http://hdl.handle.net/2158/850912.

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Valente, Cláudia Sofia dos Santos 1975. "Potential irreversible inhibitors of cysteine proteases based on sultam and naphthoquinone scaffolds." Doctoral thesis, 2007. http://hdl.handle.net/10451/277.

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40

Shanmugasundaram, Shobana. "Fabrication of nanofiber scaffolds by electrospinning and it's potential for tissue engineering." Thesis, 2004. http://library1.njit.edu/etd/fromwebvoyage.cfm?id=njit-etd2004-069.

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Ku, Wen-Xin, and 古文昕. "Pharmacophore- and structure-based virtual screening of potential Kv1.3 inhibitors with new scaffolds." Thesis, 2011. http://ndltd.ncl.edu.tw/handle/mtn4zz.

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碩士
國立臺北科技大學
生物科技研究所
99
In addition to KCa3.1, Kv1.3 has been regarded as a promising target for the selective inhibition of terminally differentiated effector memory T (TEM) cell in T cell-mediated autoimmune diseases, such as multiple sclerosis and type 1 diabetes. In this study, pharmacophore-based virtual screening was used to search for new lead compounds with new scaffolds that can serve as potential drugs without causing liver toxicity. A total of 106 Kv1.3 inhibitors, which were collected from published literatures, were used to build pharmacophore model. The best pharmacophore model (Hypo3-3), containing of two hydrogen bond acceptor, one hydrophobic, and one aromatic ring, has the highest R2 value (0.763) for the test set. The cross validation method with 95% confidence level was further used to validate Hypo3-3 and proved that this model was reliable in identifying structurally diverse compounds for Kv1.3 inhibition. This model was then employed as a filter to search for lead compounds with new scaffolds from the NCI chemical database. Top 10 hit compounds, selected based on their fit values, were found to share different conformations. On the other hand, the potent and selective Kv1.3 inhibitors can be retrieved by structure-based virtual screening. In the beginning, the Kv1.3 structure was build by homology modeling using the highest resolution structure of Kv1.2 as the template. Then, PAP-1, Psora-4 and 7-substituted khelliones inhibitors with selectivity for Kv1.3 were collected to construct a consensus scoring function with highly predicative ability by molecular docking. After docking ligand from commercially available database, this consensus scoring function was used to discover the novel selective Kv1.3 inhibitors. The resulting hit compounds from both ligand- and structure-based virtual screening can be applied in further in vitro biological evaluation and optimization.

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Lin, Ting-Yu, and 林庭宇. "Evaluation of Chondrogenic Differentiation Potential of Human Mesenchymal Stem Cells Grown in Tissue Engineering Scaffolds." Thesis, 2012. http://ndltd.ncl.edu.tw/handle/06982406708395512361.

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碩士
國立臺灣大學
高分子科學與工程學研究所
100
The chondrogenesis differentiation potential of mesenchymal stem cells (MSC) isolated from four different human tissues were compared on two biomaterials, type II collagen-hyaluronan composite (CII-HA) films and small intestinal submucosa (SIS) sheets. The four human MSCs were bone marrow-derived mesenchymal stem cells (BMSC), adipose-derived adult stem cells (ADAS), gingival fibroblasts (GF) and placenta-derived mesenchymal stem cells (PDMC). The CII-HA composite films or three-dimensional (3D) scaffold were fabricated in this study. Upon TGF-β3 induction, PDMC demonstrated the best chondrogenesis differentiation potential on both materials, followed by GF. PDMC and GF were further seeded in CII-HA composite scaffolds and 8-layer SIS scaffolds for evaluation of neocartilage formation in vitro. After 28 days, CII-HA composite scaffolds seeded with either MSCs were surfaced with a cartilaginous-like layer. Histology also showed better neocartilage formation when MSCs were grown in CII-HA composite scaffolds. NOD SCID mice subcutaneous implantation further confirmed that the combination of PDMC and CII-HA composite scaffolds promoted the formation of tissue-engineered cartilage.

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Chavarria, Daniel Freitas. "Development of new chemical entities based on natural scaffolds with therapeutic potential towards age-related disorders." Doctoral thesis, 2020. https://hdl.handle.net/10216/125620.

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Chavarria, Daniel Freitas. "Development of new chemical entities based on natural scaffolds with therapeutic potential towards age-related disorders." Tese, 2020. https://hdl.handle.net/10216/125620.

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45

Pinto, A. R. "Potential of human bone marrow derived stem cells combined with chitosan based biodegradable scaffolds for bone tissue engineering." Doctoral thesis, 2011. http://hdl.handle.net/1822/12361.

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Tese de doutoramento em Engenharia de Tecidos, Medicina Regenerativa e Células Estaminais
Bone tissue engineering has emerged as a promising alternative in cases of bone loss, overcoming problems of rejection and donor scarcity associated to the clinical used bone grafts (autografts, allografts and xenografts). By combining threedimensional structures (3D) – scaffolds, autologous cells and growth factors, bone tissue engineering seeks to achieve a long lasting and fully functional regeneration of bone. The selected scaffold should be biodegradable, allowing cells to adhere, proliferate and differentiate into the osteogenic phenotype, producing a mineralized extracellular matrix (ECM), to be later implanted into the bone defect. The rate of degradation of the scaffold should, therefore, be compatible to the rate of neo-tissue ingrowth. The rationale of the experimental work of this thesis was designed to study a bone tissue engineering strategy by combining chitosan based scaffolds and human bone marrow mesenchymal stem cells (hBMSCs), aiming bone tissue regeneration. Blends of chitosan with different types aliphatic polyesters were produced by extrusion. Afterwards, scaffolds were produced by compression molding followed by salt leaching. Several scaffolds formulations were produced and subjected to cytotoxicity and cytocompatibility tests, allowing selecting the most suitable formulation in terms of biological response. From the results obtained, the chitosanpoly( butylene succinate) (PBS) formulation presented the most promising results in in vitro cell studies with relevant cell lines. To understand why this formulation has enhanced cell performance, several formulations using different percentages of chitosan (0, 25 and 50%) and PBS (100, 75 and 50%) were used to produce scaffolds. The influence of chitosan content was evaluated with hBMSCs in vitro. All in vitro results evidenced a better performance for the highest chitosan containing scaffolds, as for cell adhesion and proliferation, as for osteogenic differentiation. Scaffolds containing chitosan (50% chitosan-50% PBS) and without chitosan (100% PBS) were implanted in different anatomic regions (cranial defect, auricular pocket and submuscular) of rats. The tissue response was evaluated by studying the inflammatory response to the implanted scaffolds. Again, scaffolds with higher chitosan amounts evidenced superior results, with a mild inflammatory response without cell necrosis, in vivo, as compared to PBS scaffolds, that evidenced tissue necrosis in all implantation regions. A different morphology of chitosan-PBS scaffolds was developed by fiber bonding to improve the porous structure. These scaffolds were clearly non-cytotoxic and cytocompatible. Furthermore, chitosan-PBS scaffolds seeded and cultured with hBMSCs in osteogenic conditions, showed an excellent cell performance. The biodegradation of chitosan-PBS scaffolds was assessed in vitro using enzymes responsible for the degradation of chitosan (lysozyme) and PBS (lipase), in similar concentrations to the ones found in human body. The cocktail of both enzymes induced a superior effect on the scaffolds biodegradation. The in vivo biodegradation and biocompatibility of the scaffolds were evaluated. The in vivo model applied to this study was the rat subcutaneous model. Results showed that the in vivo degradation was much slower than in vitro. The host tissue response was the typically associated with biomaterialsʼ implantation, with the presence of foreign body giant cells and an inflammatory response that progressed over time. The in vivo response was similar to those observed for biodegradable fixation devices or bioresorbable sutures. The final study included in this thesis was performed to confirm the tissue engineering strategy followed in this work. The potential of chitosan-PBS scaffolds combined with hBMSCs, as previously demonstrated, was studied in a relevant animal model. A critical size cranial defect in nude mice was used. This model allowed evaluating the in vivo matured construct using human cells. The results showed that constructs were able to promote bone regeneration in a superior level than scaffolds without cells. The strategy followed under the scope of this PhD thesis was successfully validated in this small animal model, using a combination of chitosan-poly(butylene succinate) scaffolds with hBMSCs.
A área de engenharia de tecidos ósseos surgiu como uma alternativa de tratamento em casos clínicos de perdas ósseas, evitando problemas de rejeição e morbidez associada a enxertos ósseos obtidos do próprio paciente. Combinando estruturas tridimensionais (3D) porosas, células autólogas e factores de crescimento, a engenharia de tecidos ósseos visa encontrar soluções para a regeneração de osso neste tipo de pacientes. O suporte 3D seleccionado deverá ser biodegradável, permitindo a adesão, proliferação e diferenciação osteogénica das células, de forma a produzir uma matriz extracelular mineralizada, sendo posteriormente implantada no defeito ósseo. A taxa de degradação do suporte 3D poroso deverá ser compatível com a taxa de regeneração do tecido ósseo O objectivo do trabalho experimental desenvolvido nesta tese foi planeado de forma validar uma estratégia de engenharia de tecidos ósseos, através da combinação de suportes 3D porosos biodegradáveis à base de quitosano e células estaminais adultas de origem humana obtidas a partir de medula óssea. Neste trabalho foram produzidas várias misturas de quitosano com diferentes tipos de poliésteres alifáticos usando a técnica de extrusão. Usando estas misturas desenvolveram-se suportes tridimensionais que foram processados por moldação por compressão com partículas de sacrifício de sal. As misturas produzidas foram avaliadas em termos de citotoxicidade e citocompatibilidade. Desta forma, foi possível seleccionar a formulação mais adequada em termos de resposta biológica. A formulação de quitosano e polibutileno succinato (PBS) foi a formulação seleccionada para posterior desenvolvimento da estratégia de engenharia de tecidos. Por ter tido consistentemente os melhores resultados biológicos in vitro, a mistura seleccionada foi usada para produzir suportes porosos contendo diferentes percentagens de quitosano (0, 25 and 50%) e PBS, de forma a estudar a importância do quitosano nas formulações. A influência da percentagem de quitosano nos suportes porosos foi avaliada através de estudos in vitro com culturas primárias de células estaminais mesenquimais de origem humana. Os resultados celulares obtidos mostraram um melhor desempenho em termos de adesão e proliferação, assim como na diferenciação osteogénica das células nos suportes 3D com maior percentagem de quitosano. Tendo-se observado uma maior eficácia no desempenho biológico dos suportes porosos contendo quitosano, interessava confirmar estes resultados in vivo, tendo como controlo suportes sem quitosano, só com PBS. Suportes porosos sem quitosano e com quitosano (50%), uma vez que foram aqueles para os quais se obteve o pior e o melhor comportamento celular in vivo respectivamente, foram implantados em diferentes regiões anatómicas (defeito craniano, implantação auricular e submuscular) em ratos. A resposta inflamatória foi avaliada, tendo os suportes porosos com quitosano evidenciado uma resposta inflamatória moderada, não se observando necrose celular. Suportes porosos com apenas PBS na sua constituição, mostraram necrose celular em todos os locais anatómicos implantados.O passo seguinte passou por optimizar a morfologia dos suportes, tendo sido neste caso desenvolvida uma estrutura porosa de malha de fibras de quitosano e PBS, por compressão a quente. Estes suportes porosos foram avaliados e confirmou-se também que não eram citotóxicos e que eram citocompatíveis. Adicionalmente, foram cultivadas células primárias humanas de medula óssea nestas estruturas tridimensionais, em condições de diferenciação osteogénica, mostrando um excelente desempenho in vitro. A biodegradação destes suportes porosos de quitosano-PBS foi estudada usando enzimas responsáveis pela degradação do quitosano (lisozima) e PBS (lipase) em concentrações idênticas às encontradas no corpo humano. Os resultados obtidos mostraram que um cocktail das duas enzimas teve um efeito pronunciado no que respeita à taxa de degradação dos suportes porosos. O estudo foi complementado pela análise da biodegradação e biocompatibilidade dos suportes tridimensionais in vivo. O modelo in vivo escolhido para este estudo foi o implante subcutâneo em ratos. Os resultados obtidos mostraram que a taxa de degradação in vivo foi consideravelmente menor comparativamente com os estudos efectuados in vitro. A resposta in vivo foi semelhante à observada em implantes de placas de fixação óssea biodegradáveis ou em suturas bioabsorvíveis. O último estudo incluído nesta tese foi realizado para confirmar a estratégia de engenharia de tecidos proposta neste trabalho: a associação de suportes porosos biodegradáveis de quitosano e PBS e células estaminais humanas de medula óssea diferenciadas para a linhagem osteogénica. O potencial desta estratégia foi estudado num modelo animal relevante: um defeito craniano de tamanho crítico em ratinhos imunocomprometidos. Este modelo permitiu avaliar o efeito da implantação dos suportes porosos cultivados com células humanas naqueles defeitos ósseos. Os resultados obtidos mostraram que esta associação de suportes porosos de quitosano-PBS com células humanas pré-cultivados in vitro em condições osteogénicas, promoveram regeneração óssea de uma forma mais significativa quando comparados com suportes porosos implantados sem células. A estratégia de engenharia de tecidos seguida no âmbito desta tese de doutoramento, através da combinação de suportes porosos de quitosano-PBS e células estaminais humanas de medula óssea foi validada com sucesso neste modelo animal de pequeno porte.

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46

(9874484), PJP Foley. "DNA bis-intercalators: Design, synthesis and DNA binding properties of potential anti-cancer agents based on rigid polynorbornyl molecular scaffolds." Thesis, 2001. https://figshare.com/articles/thesis/DNA_bis-intercalators_Design_synthesis_and_DNA_binding_properties_of_potential_anti-cancer_agents_based_on_rigid_polynorbornyl_molecular_scaffolds/13423973.

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DNA bis-intercalating agents constitute an important class of compounds for cancer chemotherapy. The work presented in this dissertation deals with the synthesis of a new class of DNA bis-intercalating agents of type I containing rigid polynorbomyl molecular frameworks. The highly rigid molecular framework is designed to place and orient the two intercalating chromophores (the DNA-reactive entities) optimally for specific binding to a known nucleotide sequence. The chromophores are attached to the rigid framework via short flexible tethers, allowing some degree of conformational mobility while maintaining well-defined maximum and minimum inter-chromophore separations. A modular approach to synthesis has been adopted to prepare the bis-intercalators that involved initial preparation of a series of complementary A-BLOCKs II and B-BLOCKIII (Scheme I), each of which contains one intercalating chromophore. These BLOCKs contain different end-functionality (A-BLOCK: alkene; B-BLOCK: epoxide) which react with each other stereospecifically, but not with themselves to produce the desired product IV. The wide range of topologically well defined products generated by this approach show variations which include spacer length, chromophore type and nature of the tether joining the chromophores to the rigid molecular framework. In particular, the BLOCK approach has permitted the preparation of the most comprehensive range of asymmetrical bis-intercalators containing rigid spacers yet described. Representative products derived from this methodology, include the bisacridine V and the acridine-naphthalimide mixed derivative VI. In addition, significant advances have been made to control the hydrophilicity of these drugs, thereby enhancing the bio-compatibility of these novel molecules. DNA binding experiments have been performed on the bis-intercalators prepared in this study. Polynucleotide structural selectivity was observed and sequence-selectivity was associated with the binding of two of the compounds with the highest affinity for DNA. Some features that enhance binding selectivity and affinity have been identified so that the synthesis of more selective compounds for effective gene targeting in chemotherapy can proceed in the future. The results which have helped to define more clearly the parameters of drug-DNA interaction represent a good example of how organic chemistry can be a useful tool to help elucidate and understand biological phenomena. The ground work has been completed providing a solid foundation from which the preparation of novel synthetic targets of medicinal interest using the BLOCK coupling concept can now be approached with less trepidation.

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"Characterization of decellularized adipose tissue hydrogel and analysis of its regenerative potential in mouse femoral defect model." Tulane University, 2020.

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archives@tulane.edu
Hydrogels serve as three-dimensional scaffolds whose composition can be customized to allow the attachment and proliferation of several different cell types. Decellularized tissue-derived scaffolds are considered close replicates of the tissue microenvironment. Decellularized adipose tissue (DAT) hydrogel has proven to be a useful tool for tissue engineering applications in pre-clinical models. The first aim of the present study was to characterize the biochemical composition of DAT hydrogel. The DAT hydrogel was prepared by processing adipose tissue acquired from three female human donors, and subsequently quantitatively analyzed using liquid chromatography-mass spectrometry (LC-MS). The enriched and depleted proteins were determined in DAT hydrogel and further analyzed by gene ontology (GO) analysis. Extracellular matrix proteins were found to be enriched, while cellular proteins were depleted relative to native adipose tissue. Furthermore, GO analysis identified that the enriched proteins could affect various biological processes via the regulation of a range of cellular pathways. The second aim was focused on the analysis of the effect of adipose-derived stromal/stem cells (ASCs) and DAT hydrogel interaction on cell morphology, proliferation, differentiation, and hydrogel microstructure. The ASCs seeded in DAT hydrogel remained viable and displayed proliferation. The adipogenic and osteogenic differentiation of ASCs seeded in DAT hydrogel was confirmed by marker gene expression and histochemical staining. Moreover, ASC attachment and differentiation altered the fibril arrangement, which indicated remodeling of the DAT hydrogel. The third aim was to analyze the regenerative potential of DAT hydrogel in a critical-sized mouse femoral defect model. The DAT hydrogel alone, or its composites with ASCs, osteo-induced ASCs (OIASC), and hydroxyapatite were tested for the ability to mediate repair of the femoral defect. The data indicated that DAT hydrogel promoted bone regeneration alone, while the regeneration was enhanced in the presence of OIASCs and hydroxyapatite. In summary, the current findings confirm that DAT hydrogel is a cytocompatible and bio-active scaffold, with potential utility as an off-the-shelf product for tissue engineering applications. In future, the analysis of DAT hydrogel using a wider range of donors representing different body mass index, age, gender, and ethnicity will provide a more comprehensive characterization.
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Omair A. Mohiuddin

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Gouveia, Analuce Canha. "Osteogenic Potential of Human Wharton’s Jelly Stromal Cells Cultured on Hierarchical Fibrous-Based Scaffold." Master's thesis, 2010. http://hdl.handle.net/10348/2174.

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Dissertação de Mestrado em Genética Molecular Comparativa e Tecnológica
A Engenharia de Tecidos é um novo conceito que surgiu como uma estratégia alternativa às terapias actuais aplicadas nas desordens musculoesqueléticas. Esta estratégia difere da transplantação de órgãos pela regeneração do tecido do próprio paciente, evitando assim a rejeição imunológica e a fraca biocompatibilidade. Na estratégia de engenharia de tecidos desenvolvida pelo Grupo de Investigação 3Bs, o scaffold desempenha um papel crítico. A arquitectura do scaffold é uma característica importante pois permite modular a resposta biológica ao respectivo scaffold. Apesar da completa interconectividade que caracteriza os scaffolds produzidos por prototipagem rápida (RP), a baixa eficiência de seeding continua a ser uma limitação para aplicações de engenharia de tecidos. Uma solução possivel para esta limitação é a integração de nanofibras nas estruturas de prototipagem. Os scaffolds hierarquicos (6 RP+ 5NFM) são obtidos pela combinação de microfibras e nanofibras, produzidas respectivamente por prototipagem rápida e electrospinning. Este estudo demonstrou que estes scaffold à base de SPCL são favoráveis para as estratégias de engenharia de tecidos. As imagens de Microscopia Eletrónica de Varrimento e Hematoxilina-Eosina provam que a integração das nanofibras nos scaffold RP melhora a eficiência de seeding. Estas imagens também demonstraram que hWJSCs aderiram preferencialmente às malhas de nanofibras. Além disso, as células foram capazes de se multiplicar e colonizar as regiões internas dos scaffolds. Este facto indica que a porosidade e interconectividade dos scaffolds produzidos são suficientes para a infiltração de células. A quantificação de DNA e os ensaios de viabilidade (MTS) também corroboram a hipótese destes scaffolds serem uma válida alternativa aos scaffolds de prototipagem rápida. O potencial osteogénico das construções celulares formadas pelos scaffolds 6 RP+NFM e hWJSCs foi comprovado pelos níveis mais elevados de ALP, o que indica uma diferenciação precoce das hWJSCs. No espectro de EDS é possivel detectar a presença de iões cálcio e fósforo o que confirma a minerilização destas construções celulares. A diferenciação osteogénica também foi confirmada pela análise de PCR em Tempo Real. Após 3 semanas de cultura, é possivel a detecção de sobreexpressão de genes associados à diferenciação osteogénica tais como RUNX2, SP7, BGLAP, SPP1 e IBSP. Finalmente, dadas às inúmeras vantagens das hWJSCs e o potencial osteogénico das mesmas quando colocadas em scaffolds 6RP e em scaffolds 6RP+5NFM, esta fonte de células estaminais adultas é uma alternativa promissora para as estratégias de engenharia de tecido ósseo.
Tissue engineering is a new concept emerged as an alternative approach to tissue and organ reconstruction. It differs from organ transplantation by regenerating patient’s own tissue and organs avoiding the biocompatibility and low biofunctionality problems as well as severe immune rejection; which are the main problems of organ transplantation. In tissue engineering approach developed in 3Bs Research Group, the scaffold performs a critical role. The architecture of the tissue engineered scaffold is an important factor to take into consideration that can modulate biological response and the clinical success of the scaffold. Despite the periodical and completely interconnected pore network that characterizes rapid prototyped (RP) scaffolds, cell seeding efficiency still remains a critical factor for optimal tissue engineering applications. Hierarchical fibrous scaffolds, obtained by the combination of RP micro- and electrospun nano-motifs, have been considered a solution to overcome this drawback. This study demonstrated that hierarchical starch-based fibrous scaffolds are favorable for tissue engineering strategies and represent a solution to overcome the cell seeding limitation of rapid prototyped scaffolds. SEM micrographs and HE images prove that the integration of nanofiber meshes into 3D RP scaffolds improved the seeding performance, as they functioned as a cell entrapment system. SEM micrographs demonstrated that hWJSCs adhered preferentially to the nanofiber meshes. Moreover, cells were able to proliferate and colonize the inner regions of the scaffolds, highlighting that the porosity and interconnectivity of the developed scaffolds allow better cell infiltration and ingrowth than the traditional RP scaffolds. Our hypothesis that integration of nanofiber meshes enhances the cell seeding efficiency and provides a better environment for cell growth is also corroborated by the results of MTS viability assay and DNA quantification. Besides the chondrogenic potential of this scaffolds have already been proved, this work also demonstrates their osteogenic potential. Higher levels of ALP expression in WJSCs RP+NFM constructs were detected the second week, reflecting the cells early osteogenic differentiation stage. Moreover EDS spectra showed the presence of calcium and phosphorous elements at the surface of the cell cultured scaffolds, confirming the mineralization. Ultimately osteogenic differentiation of hWJSCs onto RP and RP+NFM scaffolds was demonstrated by Real Time Quantitative-PCR. After 3 weeks of culture, hWJSCs showed upregulation of genes linked to osteogenic differentiation such as transcription factors RUNX2 and SP7, and the matrix proteins BGLAP, SPP1, IBSP. Furthermore, a significantly higher fold change of these genes was detected on hWJSCs RP+NFM constructs, when compared to hWJSCs RP constructs. Concomitantly, given the numerous advantages of adult stem cells as cell source and their successful osteogenesis in 3D polymeric structures, hWJSCs may be a promising alternative for bone tissue engineering strategies.

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Wu, Yi-Jhen, and 吳宜真. "Effects of scaffold porosity on angiogenesis and its potential application on hepatic fibrosis therapy." Thesis, 2018. http://ndltd.ncl.edu.tw/handle/zu5u26.

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博士
義守大學
電機工程學系
106
In general, Porous 3D scaffold has merits of providing larger surface and interconnection for cell growth and thereafter to generate tissues. The properties, pore size, pore geometry and the interconnection of pores all affect the cellular growth and differentiation of culture cells. Till today, It is very difficulty to prepare big pore size （＞300 µm）and good interconnection 3D porous scaffolds, especially for collagen biomaterials. In this present study, we prepared collagen scaffolds with various pore sizes and geometries and to evaluate the effects on cultured cells, angiogenesis and liver fibrosis repair. The obtained results indicated that we could produce average 80 µm pore size and good interconnection 3D collagen scaffold. Furthermore, we could produce more large pore size, about 500 µm, collagen scaffold by using alginate microspheres as porogen materials. The prepared collagen scaffolds all with good interconnection and with 99% water content. The porosity could be varied by using different alginate microspheres porogen and with a range of 70% -90%. The cell culture results showed that ADSCs grew well on large pore size collagen scaffolds. The ADSCs number did not change significantly after ultrasound stimulus. From SEM observation, the cell number increased obviously on ADSCs/Liver cell/HUVECs co-culture groups after ultrasound stimulus. The co-cultured cells grew better on the small pore size/mixed pore size collagen scaffolds; besides, ultrasound stimulus would influence the growth of cells. From confocal microscopy observation, the ADSCs expressed un-differentiated CD49d protein expression after 28-d culturing. The SD rats had obvious angiogenesis on the collagen scaffolds that implanted in the dorsal site after 4-w ultrasound stimulus. The liver repair and angiogenesis also appealed on rats that fibrotic liver implanted with small pore size collagen scaffolds.

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Ramírez, Vicéns Magaly Alexandra. "Cellulose nanocrystals reinforced electrospun poly(lactic acid) fibers as potential scaffold for bone tissure engineering." 2010. http://www.lib.ncsu.edu/theses/available/etd-04012010-153822/unrestricted/etd.pdf.

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Dissertations / Theses on the topic 'Potential Scaffolds'

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