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1
Massai, Diana, Francesco Pennella, Piergiorgio Gentile, Diego Gallo, Gianluca Ciardelli, Cristina Bignardi, Alberto Audenino, and Umberto Morbiducci. "Image-Based Three-Dimensional Analysis to Characterize the Texture of Porous Scaffolds." BioMed Research International 2014 (2014): 1–8. http://dx.doi.org/10.1155/2014/161437.
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The aim of the present study is to characterize the microstructure of composite scaffolds for bone tissue regeneration containing different ratios of chitosan/gelatin blend and bioactive glasses. Starting from realistic 3D models of the scaffolds reconstructed from micro-CT images, the level of heterogeneity of scaffold architecture is evaluated performing a lacunarity analysis. The results demonstrate that the presence of the bioactive glass component affects not only macroscopic features such as porosity, but mainly scaffold microarchitecture giving rise to structural heterogeneity, which could have an impact on the local cell-scaffold interaction and scaffold performances. The adopted approach allows to investigate the scale-dependent pore distribution within the scaffold and the related structural heterogeneity features, providing a comprehensive characterization of the scaffold texture.
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Gao, Han Jun, Hao Yuan, Jian Qiang Xia, Hong Wei Li, and Yi Du Zhang. "Design and Simulation of Ti6Al4V Cartilage Scaffold Based on Additive Manufacturing Technology." Materials Science Forum 1032 (May 2021): 114–19. http://dx.doi.org/10.4028/www.scientific.net/msf.1032.114.
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The combination of additive manufacturing technology and cartilage tissue scaffold construction provides a new way for clinical treatment of cartilage injury. The high priority of the cartilage scaffold is closely related to the excellent biomechanical properties, fatigue life and medical performance. In this paper, three kinds of cartilage scaffolds are designed, and three-dimensional parametric geometric and numerical simulation models are established. Based on the simulation analysis and comparison of the three kinds of scaffolds, a scaffold model is finally determined. The porosity reaches 87.38%, the equivalent elastic modulus is 9.64Gpa, and it has permanent fatigue life in service environment. It concluded that the designed Ti6Al4V titanium alloy scaffold is suitable for cartilage transplantation.
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Farina, Erica, Dario Gastaldi, Francesco Baino, Enrica Vernè, Jonathan Massera, Gissur Orlygsson, and Pasquale Vena. "Micro computed tomography based finite element models for elastic and strength properties of 3D printed glass scaffolds." Acta Mechanica Sinica 37, no. 2 (February 2021): 292–306. http://dx.doi.org/10.1007/s10409-021-01065-3.
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Abstract In this study, the mechanical properties of glass scaffolds manufactured by robocasting are investigated through micro computed tomography ($$\mu -CT$$ μ - C T ) based finite element modeling. The scaffolds are obtained by printing fibers along two perpendicular directions on parallel layers with a $$90^\circ $$ 90 ∘ tilting between two adjacent layers. A parametric study is first presented with the purpose to assess the effect of the major design parameters on the elastic and strength properties of the scaffold; the mechanical properties of the 3D printed scaffolds are eventually estimated by using the $$\mu -CT$$ μ - C T data with the aim of assessing the effect of defects on the final geometry which are intrinsic in the manufacturing process. The macroscopic elastic modulus and strength of the scaffold are determined by simulating a uniaxial compressive test along the direction which is perpendicular to the layers of the printed fibers. An iterative approach has been used in order to determine the scaffold strength. A partial validation of the computational model has been obtained through comparison of the computed results with experimental values presented in [10] on a ceramic scaffold having the same geometry. All the results have been presented as non-dimensional values. The finite element analyses have shown which of the selected design parameters have the major effect on the stiffness and strength, being the porosity and fiber shifting between adjacent layers the most important ones. The analyses carried out on the basis of the $$\mu -CT$$ μ - C T data have shown elastic modulus and strength which are consistent with that found on ideal geometry at similar macroscopic porosity. Graphic Abstract In this work, elastic and strength properties of glass-ceramic Bone Tissue Engineering scaffolds manufactured by robocasting are investigated through micro-CT based finite element models. An incremental simulation using a multi-grid finite element solver has been implemented to perform a parametric study on the effect of the major geometrical parameters of the scaffold design as well as the effect. Eventually, the effect of the geometrical imperfections deriving from the 3D printing process has been investigated by means of micro-CT image-based models. The porosity and the shifting between adjacent layers play the dominant role in determing elasticity and strength of the scaffolds. The elastic and strength properties of 3D-printed real scaffold were assessed to be consistent those obtained from the idealized geometric models, at least for the subdomain used in this study.
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Damerau, Alexandra, Frank Buttgereit, and Timo Gaber. "Optimization of a Tricalcium Phosphate-Based Bone Model Using Cell-Sheet Technology to Simulate Bone Disorders." Processes 10, no. 3 (March 11, 2022): 550. http://dx.doi.org/10.3390/pr10030550.
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Bone diseases such as osteoporosis, delayed or impaired bone healing, and osteoarthritis still represent a social, financial, and personal burden for affected patients and society. Fully humanized in vitro 3D models of cancellous bone tissue are needed to develop new treatment strategies and meet patient-specific needs. Here, we demonstrate a successful cell-sheet-based process for optimized mesenchymal stromal cell (MSC) seeding on a β-tricalcium phosphate (TCP) scaffold to generate 3D models of cancellous bone tissue. Therefore, we seeded MSCs onto the β-TCP scaffold, induced osteogenic differentiation, and wrapped a single osteogenically induced MSC sheet around the pre-seeded scaffold. Comparing the wrapped with an unwrapped scaffold, we did not detect any differences in cell viability and structural integrity but a higher cell seeding rate with osteoid-like granular structures, an indicator of enhanced calcification. Finally, gene expression analysis showed a reduction in chondrogenic and adipogenic markers, but an increase in osteogenic markers in MSCs seeded on wrapped scaffolds. We conclude from these data that additional wrapping of pre-seeded scaffolds will provide a local niche that enhances osteogenic differentiation while repressing chondrogenic and adipogenic differentiation. This approach will eventually lead to optimized preclinical in vitro 3D models of cancellous bone tissue to develop new treatment strategies.
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Valdoz, Jonard Corpuz, Benjamin C. Johnson, Dallin J. Jacobs, Nicholas A. Franks, Ethan L. Dodson, Cecilia Sanders, Collin G. Cribbs, and Pam M. Van Ry. "The ECM: To Scaffold, or Not to Scaffold, That Is the Question." International Journal of Molecular Sciences 22, no. 23 (November 24, 2021): 12690. http://dx.doi.org/10.3390/ijms222312690.
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The extracellular matrix (ECM) has pleiotropic effects, ranging from cell adhesion to cell survival. In tissue engineering, the use of ECM and ECM-like scaffolds has separated the field into two distinct areas—scaffold-based and scaffold-free. Scaffold-free techniques are used in creating reproducible cell aggregates which have massive potential for high-throughput, reproducible drug screening and disease modeling. Though, the lack of ECM prevents certain cells from surviving and proliferating. Thus, tissue engineers use scaffolds to mimic the native ECM and produce organotypic models which show more reliability in disease modeling. However, scaffold-based techniques come at a trade-off of reproducibility and throughput. To bridge the tissue engineering dichotomy, we posit that finding novel ways to incorporate the ECM in scaffold-free cultures can synergize these two disparate techniques.
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Rojas-Rojas, Laura, María Laura Espinoza-Álvarez, Silvia Castro-Piedra, Andrea Ulloa-Fernández, Walter Vargas-Segura, and Teodolito Guillén-Girón. "Muscle-like Scaffolds for Biomechanical Stimulation in a Custom-Built Bioreactor." Polymers 14, no. 24 (December 11, 2022): 5427. http://dx.doi.org/10.3390/polym14245427.
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Tissue engineering aims to develop in-vitro substitutes of native tissues. One approach of tissue engineering relies on using bioreactors combined with biomimetic scaffolds to produce study models or in-vitro substitutes. Bioreactors provide control over environmental parameters, place and hold a scaffold under desired characteristics, and apply mechanical stimulation to scaffolds. Polymers are often used for fabricating tissue-engineering scaffolds. In this study, polycaprolactone (PCL) collagen-coated microfilament scaffolds were cell-seeded with C2C12 myoblasts; then, these were grown inside a custom-built bioreactor. Cell attachment and proliferation on the scaffolds were investigated. A loading pattern was used for mechanical stimulation of the cell-seeded scaffolds. Results showed that the microfilaments provided a suitable scaffold for myoblast anchorage and that the custom-built bioreactor provided a qualified environment for the survival of the myoblasts on the polymeric scaffold. This PCL-based microfilament scaffold located inside the bioreactor proved to be a promising structure for the study of skeletal muscle models and can be used for mechanical stimulation studies in tissue engineering applications.
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Basri, Hasan, Jimmy Deswidawansyah Nasution, Ardiyansyah Syahrom, Mohd Ayub Sulong, Amir Putra Md. Saad, Akbar Teguh Prakoso, and Faisal Aminin. "The effect to flow rate characteristic on biodegradation of bone scaffold." Malaysian Journal of Fundamental and Applied Sciences 13, no. 4-2 (December 17, 2017): 546–52. http://dx.doi.org/10.11113/mjfas.v13n4-2.843.
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This paper proposes an improved modeling approach for bone scaffolds biodegradation. In this study, the numerical analysis procedure and computer-based simulation were performed for the bone scaffolds with varying porosities in determining the wall shear stresses and the permeabilities along with their influences on the scaffolds biodegradation process while the bio-fluids flow through within followed with the change in the flow rates. Based on the experimental study by immersion testing from 0 to 72 hours of the time period, the specimens with different morphologies of the commercial bone scaffolds were collected into three groups samples of 30%, 41%, and 55% porosities. As the representative of the cancellous bone morphology, the morphological degradation was observed by using 3-D CAD scaffold models based on microcomputed tomography images. By applying the boundary conditions to the computational fluid dynamics (CFD) and the fluid-structure interaction (FSI) models, the wall shear stresses within the scaffolds due to fluid flow rates variation had been simulated and determined before and after degradation. The increase of fluid flow rates tends to raise the pressure drop for scaffold models with porosities lower than 50% before degradation. As the porosities increases, the pressure drop decreases with an increase in permeability within the scaffold. The flow rates have significant effects on scaffolds with higher pressure drops by introducing the wall shear stresses with the highest values and lower permeability. These findings indicate the importance of using accurate computational models to estimate shear stress and determine experimental conditions in perfusion bioreactors for tissue engineering more accurate results will be achieved to indicate the natural distributions of fluid flow velocity, wall shear stress, and pressure.
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Acevedo, Cristian A., Yusser Olguín, Nicole Orellana, Elizabeth Sánchez, Marzena Pepczynska, and Javier Enrione. "Anatase Incorporation to Bioactive Scaffolds Based on Salmon Gelatin and Its Effects on Muscle Cell Growth." Polymers 12, no. 9 (August 28, 2020): 1943. http://dx.doi.org/10.3390/polym12091943.
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The development of new polymer scaffolds is essential for tissue engineering and for culturing cells. The use of non-mammalian bioactive components to formulate these materials is an emerging field. In our previous work, a scaffold based on salmon gelatin was developed and tested in animal models to regenerate tissues effectively and safely. Here, the incorporation of anatase nanoparticles into this scaffold was formulated, studying the new composite structure by scanning electron microscopy, differential scanning calorimetry and dynamic mechanical analysis. The incorporation of anatase nanoparticles modified the scaffold microstructure by increasing the pore size from 208 to 239 µm and significantly changing the pore shape. The glass transition temperature changed from 46.9 to 55.8 °C, and an increase in the elastic modulus from 79.5 to 537.8 kPa was observed. The biocompatibility of the scaffolds was tested using C2C12 myoblasts, modulating their attachment and growth. The anatase nanoparticles modified the stiffness of the material, making it possible to increase the growth of myoblasts cultured onto scaffolds, which envisions their use in muscle tissue engineering.
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Peng, Liqing, Bin Zhang, Xujiang Luo, Bo Huang, Jian Zhou, Shuangpeng Jiang, Weimin Guo, et al. "Small Ruminant Models for Articular Cartilage Regeneration by Scaffold-Based Tissue Engineering." Stem Cells International 2021 (December 6, 2021): 1–14. http://dx.doi.org/10.1155/2021/5590479.
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Animal models play an important role in preclinical studies, especially in tissue engineering scaffolds for cartilage repair, which require large animal models to verify the safety and effectiveness for clinical use. The small ruminant models are most widely used in this field than other large animals because they are cost-effective, easy to raise, not to mention the fact that the aforementioned animal presents similar anatomical features to that of humans. This review discusses the experimental study of tissue engineering scaffolds for knee articular cartilage regeneration in small ruminant models. Firstly, the selection of these scaffold materials and the preparation process in vitro that have been already used in vivo are briefly reviewed. Moreover, the major factors influencing the rational design and the implementation as well as advantages and limitations of small ruminants are also demonstrated. As regards methodology, this paper applies principles and methods followed by most researchers in the process of experimental design and operation of this kind. By summarizing and comparing different therapeutic concepts, this paper offers suggestions aiming to increase the effectiveness of preclinical research using small ruminant models and improve the process of developing corresponding therapies.
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Zhou, Yang, Gillian Pereira, Yuanzhang Tang, Matthew James, and Miqin Zhang. "3D Porous Scaffold-Based High-Throughput Platform for Cancer Drug Screening." Pharmaceutics 15, no. 6 (June 9, 2023): 1691. http://dx.doi.org/10.3390/pharmaceutics15061691.
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Natural polymer-based porous scaffolds have been investigated to serve as three-dimensional (3D) tumor models for drug screening owing to their structural properties with better resemblance to human tumor microenvironments than two-dimensional (2D) cell cultures. In this study, a 3D chitosan–hyaluronic acid (CHA) composite porous scaffold with tunable pore size (60, 120 and 180 µm) was produced by freeze-drying and fabricated into a 96-array platform for high-throughput screening (HTS) of cancer therapeutics. We adopted a self-designed rapid dispensing system to handle the highly viscous CHA polymer mixture and achieved a fast and cost-effective large-batch production of the 3D HTS platform. In addition, the adjustable pore size of the scaffold can accommodate cancer cells from different sources to better mimic the in vivo malignancy. Three human glioblastoma multiforme (GBM) cell lines were tested on the scaffolds to reveal the influence of pore size on cell growth kinetics, tumor spheroid morphology, gene expression and dose-dependent drug response. Our results showed that the three GBM cell lines showed different trends of drug resistance on CHA scaffolds of varying pore size, which reflects the intertumoral heterogeneity across patients in clinical practice. Our results also demonstrated the necessity to have a tunable 3D porous scaffold for adapting the heterogeneous tumor to generate the optimal HTS outcomes. It was also found that CHA scaffolds can produce a uniform cellular response (CV < 0.15) and a wide drug screening window (Z′ > 0.5) on par with commercialized tissue culture plates, and therefore, can serve as a qualified HTS platform. This CHA scaffold-based HTS platform may provide an improved alternative to traditional 2D-cell-based HTS for future cancer study and novel drug discovery.
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ZHANG, XIANBIN, and HE GONG. "SIMULATION ON TISSUE DIFFERENTIATIONS FOR DIFFERENT ARCHITECTURE DESIGNS IN BONE TISSUE ENGINEERING SCAFFOLD BASED ON CELLULAR STRUCTURE MODEL." Journal of Mechanics in Medicine and Biology 15, no. 03 (June 2015): 1550028. http://dx.doi.org/10.1142/s0219519415500281.
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In bone tissue engineering, mechanical stimuli are among the key factors affecting cell proliferation and differentiation. This study aimed to investigate the effects of different inlet fluid velocities and axial strains on the differentiation of bone marrow mesenchymal stem cells (BMSCs) on the surface of scaffolds with different morphologies. Five three-dimensional bone scaffold architectures with 65% porosity were designed using typical cellular structural models of trabecular bone. Apparent compressive strains between 0% and 5% were applied to simulate an unconfined compression test. Strain distributions were analyzed on the wall surface of the solid model. The interstitial fluid flow at inlet velocities ranging between 0.01 mm/s and 1 mm/s was applied to interconnected pores, simulating a steady state flow in the scaffold. The shear stress distributions on the surface of the scaffolds were calculated. The differentiation of BMSCs on the surface of the scaffolds with different morphologies was predicted according to mechanoregulation theory. This study shows that different levels of mechanical stimuli can be generated as a result of different scaffold morphologies under compressive loading and fluid flow to satisfy the mechanical requirements for different bone defect sites.
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Li, Yan, Dichen Li, Bingheng Lu, Dajing Gao, and Jack Zhou. "Current status of additive manufacturing for tissue engineering scaffold." Rapid Prototyping Journal 21, no. 6 (October 19, 2015): 747–62. http://dx.doi.org/10.1108/rpj-03-2014-0029.
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Purpose – The purpose of this paper is to review the current status of additive manufacturing (AM) used for tissue engineering (TE) scaffold. AM processes are identified as an effective method for fabricating geometrically complex objects directly from computer models or three-dimensional digital representations. The use of AM technologies in the field of TE has grown rapidly in the past 10 years. Design/methodology/approach – The processes, materials, precision, applications of different AM technologies and their modified versions used for TE scaffold are presented. Additionally, future directions of AM used for TE scaffold are also discussed. Findings – There are two principal routes for the fabrication of scaffolds by AM: direct and indirect routes. According to the working principle, the AM technologies used for TE scaffold can be generally classified into: laser-based; nozzle-based; and hybrid. Although a number of materials and fabrication techniques have been developed, each AM technique is a process based on the unique property of the raw materials applied. The fabrication of TE scaffolds faces a variety of challenges, such as expanding the range of materials, improving precision and adapting to complex scaffold structures. Originality/value – This review presents the latest research regarding AM used for TE scaffold. The information available in this paper helps researchers, scholars and graduate students to get a quick overview on the recent research of AM used for TE scaffold and identify new research directions for AM in TE.
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Tomar, Akanksha, Pinar Uysal-Onganer, Pooja Basnett, Uttam Pati, and Ipsita Roy. "3D Disease Modelling of Hard and Soft Cancer Using PHA-Based Scaffolds." Cancers 14, no. 14 (July 21, 2022): 3549. http://dx.doi.org/10.3390/cancers14143549.
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Tumour cells are shown to change shape and lose polarity when they are cultured in 3D, a feature typically associated with tumour progression in vivo, thus making it significant to study cancer cells in an environment that mimics the in vivo milieu. In this study we established hard (MCF7 and MDA-MB-231, breast cancer) and soft (HCT116, colon cancer) 3D cancer tumour models utilizing a blend of P(3HO-co-3HD) and P(3HB). P(3HO-co-3HD) and P(3HB) belong to a group of natural biodegradable polyesters, PHAs, that are synthesised by microorganisms. The 3D PHA scaffolds produced, with a pore size of 30 to 300 µm, allow for nutrients to diffuse within the scaffold and provide the cells with the flexibility to distribute evenly within the scaffold and grow within the pores. Interestingly, by Day 5, MDA-MB-231 showed dispersed growth in clusters, and MCF7 cells formed an evenly dispersed dense layer, while HCT116 formed large colonies within the pockets of the 3D PHA scaffolds. Our results show Epithelial Mesenchymal Transition (EMT) marker gene expression profiles in the hard tumour cancer models. In the 3D-based PHA scaffolds, MDA-MB-231 cells expressed higher levels of Wnt-11 and mesenchymal markers, such as Snail and its downstream gene Vim mRNAs, while MCF7 cells exhibited no change in their expression. On the other hand, MCF7 cells exhibited a significantly increased E-Cadherin expression as compared to MDA-MB-231 cells. The expression levels of EMT markers were comparative to their expression reported in the tumour samples, making them good representative of cancer models. In future these models will be helpful in mimicking hypoxic tumours, in studying gene expression, cellular signalling, angiogenesis and drug response more accurately than 2D and perhaps other 3D models.
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Li, Mingke, and Wangyu Liu. "A novel parameterized digital-mask generation method for projection stereolithography in tissue engineering." Rapid Prototyping Journal 24, no. 6 (August 13, 2018): 935–44. http://dx.doi.org/10.1108/rpj-06-2017-0110.
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PurposeThe purpose of this paper is to present the novel parameterized digital-mask generation method which is aimed at enhancing bio-scaffold’s fabricating efficiency with digital micro-mirror device (DMD)-based systems.Design/methodology/approachA method to directly generate the digital masks of bio-scaffolds without modeling the entire 3D scaffold models is presented. In most of the conventional methods, it is inefficient to dynamically modify the size of the structural unit cells during design, because it relies more or less on commercial computer aided design (CAD) platforms. The method proposed in this paper can achieve high efficient parameterized design, and it is independent from any CAD platforms. The generated masks in binary bitmap format can be used by the DMD-based to achieve scaffold’s additive manufacture. In conventional methods, the Boolean operation of the external surface and the internal architectures would result in the damage of unit cells in boundary region. These damaged unit cells not only lose its original mechanical property but also cause numbers of gaps and isolated features that would reduce the geometric accuracy of the fabricated scaffolds; the proposed method in this paper provides an approach to tackle this defect.FindingsThe results show that the proposed method can improve the digital masks generation efficiency.Practical implicationsThe proposed method can serve as an effective supplement to the slicing method in additive manufacture. It also provides a way to design and fabricate scaffolds with heterogeneous architectures.Originality/valueThis paper gives supports to fabricate bio-scaffold with DMD-based systems.
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Gerschenfeld, Gaspard, Rachida Aid, Teresa Simon-Yarza, Soraya Lanouar, Patrick Charnay, Didier Letourneur, and Piotr Topilko. "Tuning Physicochemical Properties of a Macroporous Polysaccharide-Based Scaffold for 3D Neuronal Culture." International Journal of Molecular Sciences 22, no. 23 (November 25, 2021): 12726. http://dx.doi.org/10.3390/ijms222312726.
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Central nervous system (CNS) lesions are a leading cause of death and disability worldwide. Three-dimensional neural cultures in biomaterials offer more physiologically relevant models for disease studies, toxicity screenings or in vivo transplantations. Herein, we describe the development and use of pullulan/dextran polysaccharide-based scaffolds for 3D neuronal culture. We first assessed scaffolding properties upon variation of the concentration (1%, 1.5%, 3% w/w) of the cross-linking agent, sodium trimetaphosphate (STMP). The lower STMP concentration (1%) allowed us to generate scaffolds with higher porosity (59.9 ± 4.6%), faster degradation rate (5.11 ± 0.14 mg/min) and lower elastic modulus (384 ± 26 Pa) compared with 3% STMP scaffolds (47 ± 2.1%, 1.39 ± 0.03 mg/min, 916 ± 44 Pa, respectively). Using primary cultures of embryonic neurons from PGKCre, Rosa26tdTomato embryos, we observed that in 3D culture, embryonic neurons remained in aggregates within the scaffolds and did not attach, spread or differentiate. To enhance neuronal adhesion and neurite outgrowth, we then functionalized the 1% STMP scaffolds with laminin. We found that treatment of the scaffold with a 100 μg/mL solution of laminin, combined with a subsequent freeze-drying step, created a laminin mesh network that significantly enhanced embryonic neuron adhesion, neurite outgrowth and survival. Such scaffold therefore constitutes a promising neuron-compatible and biodegradable biomaterial.
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Palmroth, Aleksi, Sanna Pitkänen, Markus Hannula, Kaarlo Paakinaho, Jari Hyttinen, Susanna Miettinen, and Minna Kellomäki. "Evaluation of scaffold microstructure and comparison of cell seeding methods using micro-computed tomography-based tools." Journal of The Royal Society Interface 17, no. 165 (April 2020): 20200102. http://dx.doi.org/10.1098/rsif.2020.0102.
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Micro-computed tomography (micro-CT) provides a means to analyse and model three-dimensional (3D) tissue engineering scaffolds. This study proposes a set of micro-CT-based tools firstly for evaluating the microstructure of scaffolds and secondly for comparing different cell seeding methods. The pore size, porosity and pore interconnectivity of supercritical CO 2 processed poly( l -lactide-co- ɛ -caprolactone) (PLCL) and PLCL/β-tricalcium phosphate scaffolds were analysed using computational micro-CT models. The models were supplemented with an experimental method, where iron-labelled microspheres were seeded into the scaffolds and micro-CT imaged to assess their infiltration into the scaffolds. After examining the scaffold architecture, human adipose-derived stem cells (hASCs) were seeded into the scaffolds using five different cell seeding methods. Cell viability, number and 3D distribution were evaluated. The distribution of the cells was analysed using micro-CT by labelling the hASCs with ultrasmall paramagnetic iron oxide nanoparticles. Among the tested seeding methods, a forced fluid flow-based technique resulted in an enhanced cell infiltration throughout the scaffolds compared with static seeding. The current study provides an excellent set of tools for the development of scaffolds and for the design of 3D cell culture experiments.
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D’Andrea, Luca, Dario Gastaldi, Enrica Verné, Francesco Baino, Jonathan Massera, Gissur Örlygsson, and Pasquale Vena. "Mechanical Properties of Robocast Glass Scaffolds Assessed through Micro-CT-Based Finite Element Models." Materials 15, no. 18 (September 13, 2022): 6344. http://dx.doi.org/10.3390/ma15186344.
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In this study, the mechanical properties of two classes of robocast glass scaffolds are obtained through Computed micro-Tomography (micro-CT) based Finite Element Modeling (FEM) with the specific purpose to explicitly account for the geometrical defects introduced during manufacturing. Both classes demonstrate a fiber distribution along two perpendicular directions on parallel layers with a 90∘ tilting between two adjacent layers. The crack pattern identified upon compression loading is consistent with that found in experimental studies available in literature. The finite element models have demonstrated that the effect of imperfections on elastic and strength properties may be substantial, depending on the specific type of defect identified in the scaffolds. In particular, micro-porosity, fiber length interruption and fiber detaching were found as key factors. The micro-pores act as stress concentrators promoting fracture initiation and propagation, while fiber detachment reduces the scaffold properties substantially along the direction perpendicular to the fiber plane.
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Ahsan, AMM, Ruinan Xie, and Bashir Khoda. "Heterogeneous topology design and voxel-based bio-printing." Rapid Prototyping Journal 24, no. 7 (October 8, 2018): 1142–54. http://dx.doi.org/10.1108/rpj-05-2017-0076.
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Purpose The purpose of this paper is to present a topology-based tissue scaffold design methodology to accurately represent the heterogeneous internal architecture of tissues/organs. Design/methodology/approach An image analysis technique is used that digitizes the topology information contained in medical images of tissues/organs. A weighted topology reconstruction algorithm is implemented to represent the heterogeneity with parametric functions. The parametric functions are then used to map the spatial material distribution following voxelization. The generated chronological information yields hierarchical tool-path points which are directly transferred to the three-dimensional (3D) bio-printer through a proposed generic platform called Application Program Interface (API). This seamless data corridor between design (virtual) and fabrication (physical) ensures the manufacturability of personalized heterogeneous porous scaffold structure without any CAD/STL file. Findings The proposed methodology is implemented to verify the effectiveness of the approach and the designed example structures are bio-fabricated with a deposition-based bio-additive manufacturing system. The designed and fabricated heterogeneous structures are evaluated which shows conforming porosity distribution compared to uniform method. Originality/value In bio-fabrication process, the generated bio-models with boundary representation (B-rep) or surface tessellation (mesh) do not capture the internal architectural information. This paper provides a design methodology for scaffold structure mimicking the native tissue/organ architecture and direct fabricating the structure without reconstructing the CAD model. Therefore, designing and direct bio-printing the heterogeneous topology of tissue scaffolds from medical images minimize the disparity between the internal architecture of target tissue and its scaffold.
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Revia, Richard A., Brandon Wagner, Matthew James, and Miqin Zhang. "High-Throughput Dispensing of Viscous Solutions for Biomedical Applications." Micromachines 13, no. 10 (October 13, 2022): 1730. http://dx.doi.org/10.3390/mi13101730.
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Cells cultured in three-dimensional scaffolds express a phenotype closer to in vivo cells than cells cultured in two-dimensional containers. Natural polymers are suitable materials to make three-dimensional scaffolds to develop disease models for high-throughput drug screening owing to their excellent biocompatibility. However, natural polymer solutions have a range of viscosities, and none of the currently available liquid dispensers are capable of dispensing highly viscous polymer solutions. Here, we report the development of an automated scaffold dispensing system for rapid, reliable, and homogeneous creation of scaffolds in well-plate formats. We employ computer-controlled solenoid valves to regulate air pressure impinging upon a syringe barrel filled with scaffold solution to be dispensed. Automated dispensing of scaffold solution is achieved via a programmable software interface that coordinates solution extrusion and the movement of a dispensing head. We show that our pneumatically actuated dispensing system can evenly distribute high-viscosity, chitosan-based polymer solutions into 96- and 384-well plates to yield highly uniform three-dimensional scaffolds after lyophilization. We provide a proof-of-concept demonstration of high-throughput drug screening by culturing glioblastoma cells in scaffolds and exposing them to temozolomide. This work introduces a device that can hasten the creation of three-dimensional cell scaffolds and their application to high-throughput testing.
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SHUAI, CIJUN, ZHONGZHENG MAO, CHENGDE GAO, JINGLIN LIU, and SHUPING PENG. "DEVELOPMENT OF COMPLEX POROUS POLYVINYL ALCOHOL SCAFFOLDS: MICROSTRUCTURE, MECHANICAL, AND BIOLOGICAL EVALUATIONS." Journal of Mechanics in Medicine and Biology 13, no. 03 (May 14, 2013): 1350034. http://dx.doi.org/10.1142/s0219519413500346.
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Complex three-dimensional (3D) porous scaffolds with macro-pore size of 400–800 μm based on polyvinyl alcohol (PVA) powder were successfully developed by selective laser sintering (SLS) technology. The PVA scaffolds had customizable shape, controlled and totally interconnected porous structure, and high porosity. The microstructure and mechanical property were performed for their suitability for tissue engineering (TE). The results showed that PVA did not decompose while the degree of crystallization decreased in a given sintering condition. Moreover, there were micro-pores with sizes of 20–100 μm in the scaffold. The actual porosity of sintered scaffolds could be up to 82.35%, which was higher than the value of the designed models. An in vitro biocompatibility test showed MG-63 cells could well spread on the scaffold surface. The presented work demonstrates the favorable potential of PVA powder as TE scaffolds fabricated via SLS.
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Alghuwainem, Ayidah, Alaa T. Alshareeda, and Batla Alsowayan. "Scaffold-Free 3-D Cell Sheet Technique Bridges the Gap between 2-D Cell Culture and Animal Models." International Journal of Molecular Sciences 20, no. 19 (October 4, 2019): 4926. http://dx.doi.org/10.3390/ijms20194926.
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Various tissue engineering techniques have been created in research spanning two centuries, resulting in new opportunities for growing cells in culture and the creation of 3-D tissue-like constructs. These techniques are classified as scaffold-based and scaffold-free techniques. Cell sheet, as a scaffold-free technique, has attracted research interest in the context of drug discovery and tissue repair, because it provides more predictive data for in vivo testing. It is one of the most promising techniques and has the potential to treat degenerative tissues such as heart, kidneys, and liver. In this paper, we argue the advantages of cell sheets as a scaffold-free approach, compared to other techniques, including scaffold-based and scaffold-free techniques such as the classic systemic injection of cell suspension.
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Korpershoek, Jasmijn V., Tommy S. de Windt, Michella H. Hagmeijer, Lucienne A. Vonk, and Daniel B. F. Saris. "Cell-Based Meniscus Repair and Regeneration: At the Brink of Clinical Translation?" Orthopaedic Journal of Sports Medicine 5, no. 2 (February 1, 2017): 232596711769013. http://dx.doi.org/10.1177/2325967117690131.
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Background: Meniscus damage can be caused by trauma or degeneration and is therefore common among patients of all ages. Repair or regeneration of the menisci could be of great importance not only for pain relief or regaining function but also to prevent degenerative disease and osteoarthritis. Current treatment does not offer consistent long-term improvement. Although preclinical research focusing on augmentation of meniscal tear repair and regeneration after meniscectomy is encouraging, clinical translation remains difficult. Purpose: To systematically evaluate the literature on in vivo meniscus regeneration and explore the optimal cell sources and conditions for clinical translation. We aimed at thorough evaluation of current evidence as well as clarifying the challenges for future preclinical and clinical studies. Study Design: Systematic review. Methods: A search was conducted using the electronic databases of MEDLINE, Embase, and the Cochrane Collaboration. Search terms included meniscus, regeneration, and cell-based. Results: After screening 81 articles based on title and abstract, 51 articles on in vivo meniscus regeneration could be included; 2 additional articles were identified from the references. Repair and regeneration of the meniscus has been described by intra-articular injection of multipotent mesenchymal stromal (stem) cells from adipose tissue, bone marrow, synovium, or meniscus or the use of these cell types in combination with implantable or injectable scaffolds. The use of fibrochondrocytes, chondrocytes, and transfected myoblasts for meniscus repair and regeneration is limited to the combination with different scaffolds. The comparative in vitro and in vivo studies mentioned in this review indicate that the use of allogeneic cells is as successful as the use of autologous cells. In addition, the implantation or injection of cell-seeded scaffolds increased tissue regeneration and led to better structural organization compared with scaffold implantation or injection of a scaffold alone. None of the studies mentioned in this review compare the effectiveness of different (cell-seeded) scaffolds. Conclusion: There is heterogeneity in animal models, cell types, and scaffolds used, and limited comparative studies are available. The comparative in vivo research that is currently available is insufficient to draw strong conclusions as to which cell type is the most promising. However, there is a vast amount of in vivo research on the use of different types of multipotent mesenchymal stromal (stem) cells in different experimental settings, and good results are reported in terms of tissue formation. None of these studies compare the effectiveness of different cell-scaffold combinations, making it hard to conclude which scaffold has the greatest potential.
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Uiterwijk, M., D. C. van der Valk, R. van Vliet, I. J. de Brouwer, C. R. Hooijmans, and J. Kluin. "Pulmonary valve tissue engineering strategies in large animal models." PLOS ONE 16, no. 10 (October 5, 2021): e0258046. http://dx.doi.org/10.1371/journal.pone.0258046.
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In the last 25 years, numerous tissue engineered heart valve (TEHV) strategies have been studied in large animal models. To evaluate, qualify and summarize all available publications, we conducted a systematic review and meta-analysis. We identified 80 reports that studied TEHVs of synthetic or natural scaffolds in pulmonary position (n = 693 animals). We identified substantial heterogeneity in study designs, methods and outcomes. Most importantly, the quality assessment showed poor reporting in randomization and blinding strategies. Meta-analysis showed no differences in mortality and rate of valve regurgitation between different scaffolds or strategies. However, it revealed a higher transvalvular pressure gradient in synthetic scaffolds (11.6 mmHg; 95% CI, [7.31–15.89]) compared to natural scaffolds (4,67 mmHg; 95% CI, [3,94–5.39]; p = 0.003). These results should be interpreted with caution due to lack of a standardized control group, substantial study heterogeneity, and relatively low number of comparable studies in subgroup analyses. Based on this review, the most adequate scaffold model is still undefined. This review endorses that, to move the TEHV field forward and enable reliable comparisons, it is essential to define standardized methods and ways of reporting. This would greatly enhance the value of individual large animal studies.
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Uiterwijk, M., D. C. van der Valk, R. van Vliet, I. J. de Brouwer, C. R. Hooijmans, and J. Kluin. "Pulmonary valve tissue engineering strategies in large animal models." PLOS ONE 16, no. 10 (October 5, 2021): e0258046. http://dx.doi.org/10.1371/journal.pone.0258046.
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In the last 25 years, numerous tissue engineered heart valve (TEHV) strategies have been studied in large animal models. To evaluate, qualify and summarize all available publications, we conducted a systematic review and meta-analysis. We identified 80 reports that studied TEHVs of synthetic or natural scaffolds in pulmonary position (n = 693 animals). We identified substantial heterogeneity in study designs, methods and outcomes. Most importantly, the quality assessment showed poor reporting in randomization and blinding strategies. Meta-analysis showed no differences in mortality and rate of valve regurgitation between different scaffolds or strategies. However, it revealed a higher transvalvular pressure gradient in synthetic scaffolds (11.6 mmHg; 95% CI, [7.31–15.89]) compared to natural scaffolds (4,67 mmHg; 95% CI, [3,94–5.39]; p = 0.003). These results should be interpreted with caution due to lack of a standardized control group, substantial study heterogeneity, and relatively low number of comparable studies in subgroup analyses. Based on this review, the most adequate scaffold model is still undefined. This review endorses that, to move the TEHV field forward and enable reliable comparisons, it is essential to define standardized methods and ways of reporting. This would greatly enhance the value of individual large animal studies.
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Dias, Marlon Lemos, Bruno Andrade Paranhos, and Regina Coeli dos Santos Goldenberg. "Liver scaffolds obtained by decellularization: A transplant perspective in liver bioengineering." Journal of Tissue Engineering 13 (January 2022): 204173142211053. http://dx.doi.org/10.1177/20417314221105305.
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Liver transplantation is the only definitive treatment for many diseases that affect this organ, however, its quantity and viability are reduced. The study of liver scaffolds based on an extracellular matrix is a tissue bioengineering strategy with great application in regenerative medicine. Collectively, recent studies suggest that liver scaffold transplantation may assist in reestablishing hepatic function in preclinical diseased animals, which represents a great potential for application as a treatment for patients with liver disease in the future. This review focuses on useful strategies to promote liver scaffold transplantation and the main open questions about this context. We outline the current knowledge about ex vivo bioengineered liver transplantation, including the surgical techniques, recipient survival time, scaffold preparation before transplantation, and liver disease models. We also highlight the current limitations and future directions regarding in vivo bioengineering techniques.
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Castillo-Henríquez, Luis, Pablo Sanabria-Espinoza, Brayan Murillo-Castillo, Gabriela Montes de Oca-Vásquez, Diego Batista-Menezes, Briner Calvo-Guzmán, Nils Ramírez-Arguedas, and José Vega-Baudrit. "Topical Chitosan-Based Thermo-Responsive Scaffold Provides Dexketoprofen Trometamol Controlled Release for 24 h Use." Pharmaceutics 13, no. 12 (December 6, 2021): 2100. http://dx.doi.org/10.3390/pharmaceutics13122100.
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Chronic and non-healing wounds demand personalized and more effective therapies for treating complications and improving patient compliance. Concerning that, this work aims to develop a suitable chitosan-based thermo-responsive scaffold to provide 24 h controlled release of Dexketoprofen trometamol (DKT). Three formulation prototypes were developed using chitosan (F1), 2:1 chitosan: PVA (F2), and 1:1 chitosan:gelatin (F3). Compatibility tests were done by DSC, TG, and FT-IR. SEM was employed to examine the morphology of the surface and inner layers from the scaffolds. In vitro release studies were performed at 32 °C and 38 °C, and the profiles were later adjusted to different kinetic models for the best formulation. F3 showed the most controlled release of DKT at 32 °C for 24 h (77.75 ± 2.72%) and reduced the burst release in the initial 6 h (40.18 ± 1.00%). The formulation exhibited a lower critical solution temperature (LCST) at 34.96 °C, and due to this phase transition, an increased release was observed at 38 °C (88.52 ± 2.07% at 12 h). The release profile for this formulation fits with Hixson–Crowell and Korsmeyer–Peppas kinetic models at both temperatures. Therefore, the developed scaffold for DKT delivery performs adequate controlled release, thereby; it can potentially overcome adherence issues and complications in wound healing applications.
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Kinikoglu, Beste. "A Comparison of Scaffold-free and Scaffold-based Reconstructed Human Skin Models as Alternatives to Animal Use." Alternatives to Laboratory Animals 45, no. 6 (December 2017): 309–16. http://dx.doi.org/10.1177/026119291704500607.
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Trif, Letitiţia. "Training Models of Social Constructivism. Teaching Based on Developing A Scaffold." Procedia - Social and Behavioral Sciences 180 (May 2015): 978–83. http://dx.doi.org/10.1016/j.sbspro.2015.02.184.
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Løvset, Tyge, Dag Magne Ulvang, Tor Christian Bekkvik, Kåre Villanger, and Ivan Viola. "Rule-based method for automatic scaffold assembly from 3D building models." Computers & Graphics 37, no. 4 (June 2013): 256–68. http://dx.doi.org/10.1016/j.cag.2013.01.007.
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Mohd, Nurulhuda, Masfueh Razali, Mariyam Jameelah Ghazali, and Noor Hayaty Abu Kasim. "3D-Printed Hydroxyapatite and Tricalcium Phosphates-Based Scaffolds for Alveolar Bone Regeneration in Animal Models: A Scoping Review." Materials 15, no. 7 (April 2, 2022): 2621. http://dx.doi.org/10.3390/ma15072621.
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Three-dimensional-printed scaffolds have received greater attention as an attractive option compared to the conventional bone grafts for regeneration of alveolar bone defects. Hydroxyapatite and tricalcium phosphates have been used as biomaterials in the fabrication of 3D-printed scaffolds. This scoping review aimed to evaluate the potential of 3D-printed HA and calcium phosphates-based scaffolds on alveolar bone regeneration in animal models. The systematic search was conducted across four electronic databases: Ovid, Web of Science, PubMed and EBSCOHOST, based on PRISMA-ScR guidelines until November 2021. The inclusion criteria were: (i) animal models undergoing alveolar bone regenerative surgery, (ii) the intervention to regenerate or augment bone using 3D-printed hydroxyapatite or other calcium phosphate scaffolds and (iii) histological and microcomputed tomographic analyses of new bone formation and biological properties of 3D-printed hydroxyapatite or calcium phosphates. A total of ten studies were included in the review. All the studies showed promising results on new bone formation without any inflammatory reactions, regardless of the animal species. In conclusion, hydroxyapatite and tricalcium phosphates are feasible materials for 3D-printed scaffolds for alveolar bone regeneration and demonstrated bone regenerative potential in the oral cavity. However, further research is warranted to determine the scaffold material which mimics the gold standard of care for bone regeneration in the load-bearing areas, including the masticatory load of the oral cavity.
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Ricci, Claudio, Bahareh Azimi, Luca Panariello, Benedetta Antognoli, Beatrice Cecchini, Roberta Rovelli, Meruyert Rustembek, et al. "Assessment of Electrospun Poly(ε-caprolactone) and Poly(lactic acid) Fiber Scaffolds to Generate 3D In Vitro Models of Colorectal Adenocarcinoma: A Preliminary Study." International Journal of Molecular Sciences 24, no. 11 (May 29, 2023): 9443. http://dx.doi.org/10.3390/ijms24119443.
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Three-dimensional scaffold-based culture has been increasingly gaining influence in oncology as a therapeutic strategy for tumors with a high relapse percentage. This study aims to evaluate electrospun poly(ε-caprolactone) (PCL) and poly(lactic acid) (PLA) scaffolds to create a 3D model of colorectal adenocarcinoma. Specifically, the physico-mechanical and morphological properties of PCL and PLA electrospun fiber meshes collected at different drum velocities, i.e., 500 rpm, 1000 rpm and 2500 rpm, were assessed. Fiber size, mesh porosity, pore size distribution, water contact angle and tensile mechanical properties were investigated. Caco-2 cells were cultured on the produced PCL and PLA scaffolds for 7 days, demonstrating good cell viability and metabolic activity in all the scaffolds. A cross-analysis of the cell–scaffold interactions with morphological, mechanical and surface characterizations of the different electrospun fiber meshes was carried out, showing an opposite trend of cell metabolic activity in PLA and PCL scaffolds regardless of the fiber alignment, which increased in PLA and decreased in PCL. The best samples for Caco-2 cell culture were PCL500 (randomly oriented fibers) and PLA2500 (aligned fibers). Caco-2 cells had the highest metabolic activity in these scaffolds, with Young’s moduli in the range of 8.6–21.9 MPa. PCL500 showed Young’s modulus and strain at break close to those of the large intestine. Advancements in 3D in vitro models of colorectal adenocarcinoma could move forward the development of therapies for this cancer.
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Souto-Lopes, Mariana, Maria Helena Fernandes, Fernando Jorge Monteiro, and Christiane Laranjo Salgado. "Bioengineering Composite Aerogel-Based Scaffolds That Influence Porous Microstructure, Mechanical Properties and In Vivo Regeneration for Bone Tissue Application." Materials 16, no. 12 (June 20, 2023): 4483. http://dx.doi.org/10.3390/ma16124483.
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Tissue regeneration of large bone defects is still a clinical challenge. Bone tissue engineering employs biomimetic strategies to produce graft composite scaffolds that resemble the bone extracellular matrix to guide and promote osteogenic differentiation of the host precursor cells. Aerogel-based bone scaffold preparation methods have been increasingly improved to overcome the difficulties in balancing the need for an open highly porous and hierarchically organized microstructure with compression resistance to withstand bone physiological loads, especially in wet conditions. Moreover, these improved aerogel scaffolds have been implanted in vivo in critical bone defects, in order to test their bone regeneration potential. This review addresses recently published studies on aerogel composite (organic/inorganic)-based scaffolds, having in mind the various cutting-edge technologies and raw biomaterials used, as well as the improvements that are still a challenge in terms of their relevant properties. Finally, the lack of 3D in vitro models of bone tissue for regeneration studies is emphasized, as well as the need for further developments to overcome and minimize the requirement for studies using in vivo animal models.
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Modi, Yashwant Kumar, and Kiran Kumar Sahu. "Process parameter optimization for porosity and compressive strength of calcium sulfate based 3D printed porous bone scaffolds." Rapid Prototyping Journal 27, no. 2 (January 28, 2021): 245–55. http://dx.doi.org/10.1108/rpj-04-2020-0083.
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Purpose This study aims to optimize the process parameters of ZPrinter® 450 for measured porosity (MP) and compressive strength (CS) of calcium sulfate-based porous bone scaffold using Taguchi approach. Design/methodology/approach Initially, a porous scaffold with smallest pore size that can be de-powdered completely is identified through a pilot study. Five printing parameters, namely, layer thickness (LT), build orientation (BO), build position (BP), delay time (DT) and binder saturation (BS), each at three levels have been optimized for MP and CS of the fabricated scaffolds using L27 orthogonal array (OA), signal-to-noise ratio and analysis of variance (ANOVA). Findings The scaffolds with 600 µm pores could be de-powdered completely. Optimum levels of parameters are LT2, BO1, BP2, DT1 and BS1 for MP and LT1, BO1, BP2, DT1 and BS2 for CS. The ANOVA reveals that the BS (49.12%) is the most and BP (8.34%) is the least significant parameter for MP. LT (50.84%) is the most, BO (33.79%) is second most and DT (2.59%) is the least significant parameter for CS. Taguchi confirmation test and linear regression models indicate a good agreement between predicted and experimental values of MP and CS. The experimental values of MP and CS at the optimum levels of parameters are found 38.12% and 1.29 MPa, respectively. Originality/value The paper presents effect of process parameters of ZPrinter® 450 on MP and CS of calcium sulfate-based porous scaffolds. Results may be used as guideline for powder bed binder jetting three-dimensional printing of ceramic scaffolds.
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Cordelle, Justine, and Sara Mantero. "Insight on the endothelialization of small silk-based tissue-engineered vascular grafts." International Journal of Artificial Organs 43, no. 10 (March 7, 2020): 631–44. http://dx.doi.org/10.1177/0391398820906547.
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Along with an increased incidence of cardiovascular diseases, there is a strong need for small-diameter vascular grafts. Silk has been investigated as a biomaterial to develop such grafts thanks to different processing options. Endothelialization was shown to be extremely important to ensure graft patency and there is ongoing research on the development and behavior of endothelial cells on vascular tissue-engineered scaffolds. This article reviews the endothelialization of silk-based scaffolds processed throughout the years as silk non-woven nets, films, gel spun, electrospun, or woven scaffolds. Encouraging results were reported with these scaffolds both in vitro and in vivo when implanted in small- to middle-sized animals. The use of coatings and heparin or sulfur to enhance, respectively, cell adhesion and scaffold hemocompatibility is further presented. Bioreactors also showed their interest to improve cell adhesion and thus promoting in vitro pre-endothelialization of grafts even though they are still not systematically used. Finally, the importance of the animal models used to study the right mechanism of endothelialization is discussed.
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Ma, Hailong, Shubo Xu, Xiaoyu Jun, Aijun Tang, and Xinzhi Hu. "Finite Element Analysis of Renewable Porous Bones and Optimization of Additive Manufacturing Processes." Coatings 13, no. 5 (May 12, 2023): 912. http://dx.doi.org/10.3390/coatings13050912.
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Three-dimensional printing technology has a precise manufacturing process that can control tiny pores and can design individualized prostheses based on the patient’s own conditions. Different porous structures were designed by controlling different parameters such as porosity, using UG NX to establish models with different porosities and using ANSYS to simulate stress and strain. Unidirectional compression and stretching simulations were carried out to obtain stress, strain, and deformation. Based on these data, a porosity was found to approximate the elastic modulus of the humeral bone scaffold. As the porosity increased, the equivalent elastic modulus decreased significantly in the lateral direction, and the maximum stress formed by the porous structure and deformation increased significantly. Four different finite element models and geometric models of cubic, face-centered cubic, honeycomb, and body-centered cubic unit structures were selected. Then these porous structures were simulated for tensile and compression experiments, and the simulation results were analyzed. The forming simulation of the finite element model was carried out, and the evolution of mechanical properties of the porous structure during the 3D printing process was analyzed. The results showed that designing the humeral bone scaffold as a porous structure could reduce the stiffness of the prosthesis, alleviate stress shielding around the prosthesis after surgery, enhance its stability, and prolong its service life. The study provides reference values and scientific guidance for the feasibility of porous humeral bone scaffolds and provides a basis for the research and design of clinical humeral bone scaffolds.
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dos Santos, Kelvin Sousa, Lariane Teodoro Oliveira, Marina de Lima Fontes, Ketylin Fernanda Migliato, Ana Marisa Fusco-Almeida, Maria José Soares Mendes Giannini, and Andrei Moroz. "Alginate-Based 3D A549 Cell Culture Model to Study Paracoccidioides Infection." Journal of Fungi 9, no. 6 (May 31, 2023): 634. http://dx.doi.org/10.3390/jof9060634.
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A three-dimensional (3D) lung aggregate model based on sodium alginate scaffolds was developed to study the interactions between Paracoccidioides brasiliensis (Pb) and lung epithelial cells. The suitability of the 3D aggregate as an infection model was examined using cell viability (cytotoxicity), metabolic activity, and proliferation assays. Several studies exemplify the similarity between 3D cell cultures and living organisms, which can generate complementary data due to the greater complexity observed in these designed models, compared to 2D cell cultures. A 3D cell culture system of human A549 lung cell line plus sodium alginate was used to create the scaffolds that were infected with Pb18. Our results showed low cytotoxicity, evidence of increased cell density (indicative of cell proliferation), and the maintenance of cell viability for seven days. The confocal analysis revealed viable yeast within the 3D scaffold, as demonstrated in the solid BHI Agar medium cultivation. Moreover, when ECM proteins were added to the alginate scaffolds, the number of retrieved fungi was significantly higher. Our results highlight that this 3D model may be promising for in vitro studies of host–pathogen interactions.
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Wang, Yifan, Sunčica Čanić, Martina Bukač, Charles Blaha, and Shuvo Roy. "Mathematical and Computational Modeling of Poroelastic Cell Scaffolds Used in the Design of an Implantable Bioartificial Pancreas." Fluids 7, no. 7 (July 1, 2022): 222. http://dx.doi.org/10.3390/fluids7070222.
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We present a multi-scale mathematical model and a novel numerical solver to study blood plasma flow and oxygen concentration in a prototype model of an implantable Bioartificial Pancreas (iBAP) that operates under arteriovenous pressure differential without the need for immunosuppressive therapy. The iBAP design consists of a poroelastic cell scaffold containing the healthy transplanted cells, encapsulated between two semi-permeable nano-pore size membranes to prevent the patient’s own immune cells from attacking the transplant. The device is connected to the patient’s vascular system via an anastomosis graft bringing oxygen and nutrients to the transplanted cells of which oxygen is the limiting factor for long-term viability. Mathematically, we propose a (nolinear) fluid–poroelastic structure interaction model to describe the flow of blood plasma through the scaffold containing the cells, and a set of (nonlinear) advection–reaction–diffusion equations defined on moving domains to study oxygen supply to the cells. These macro-scale models are solved using finite element method based solvers. One of the novelties of this work is the design of a novel second-order accurate fluid–poroelastic structure interaction solver, for which we prove that it is unconditionally stable. At the micro/nano-scale, Smoothed Particle Hydrodynamics (SPH) simulations are used to capture the micro/nano-structure (architecture) of cell scaffolds and obtain macro-scale parameters, such as hydraulic conductivity/permeability, from the micro-scale scaffold-specific architecture. To avoid expensive micro-scale simulations based on SPH simulations for every new scaffold architecture, we use Encoder–Decoder Convolution Neural Networks. Based on our numerical simulations, we propose improvements in the current prototype design. For example, we show that highly elastic scaffolds have a higher capacity for oxygen transfer, which is an important finding considering that scaffold elasticity can be controlled during their fabrication, and that elastic scaffolds improve cell viability. The mathematical and computational approaches developed in this work provide a benchmark tool for computational analysis of not only iBAP, but also, more generally, of cell encapsulation strategies used in the design of devices for cell therapy and bio-artificial organs.
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Magini, Eduarda Blasi, Luiza de Oliveira Matos, Raissa Borges Curtarelli, Mariane Beatriz Sordi, Gabriel Leonardo Magrin, Carlos Flores-Mir, Reinhard Gruber, and Ariadne Cristiane Cabral Cruz. "Simvastatin Embedded into Poly(Lactic-Co-Glycolic Acid)-Based Scaffolds in Promoting Preclinical Bone Regeneration: A Systematic Review." Applied Sciences 12, no. 22 (November 16, 2022): 11623. http://dx.doi.org/10.3390/app122211623.
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Simvastatin embedded into poly(lactic-co-glycolic acid) (PLGA)-based scaffolds can stimulate bone regeneration in preclinical models. However, the ideal pharmacological dose has not been evaluated. This systematic review reports on the simvastatin doses used in preclinical studies and evaluates the regeneration of critical-sized bone defects. References were selected in a two-phase process. Electronic databases (Embase, LILACS, LIVIVO, PubMed, SCOPUS, and Web of Science) and grey literature databases (Google Scholar, Open Grey, and ProQuest) were searched until September 2022. The risk of bias was considered to be low based on the SYRCLE tool. We identified four studies in rat, two in parietal and two in calvaria bone, one in mouse parietal bone, and one in rabbit femur bone. Simvastatin, ranging from 8 to 100 µg, significantly increased bone formation in five studies, as compared to the scaffold alone based on µ-computed tomography, histomorphometric, and radiography analysis. The median increase in bone formation caused by simvastatin was 2.1-fold compared to the PLGA-based scaffold alone. There was, however, no significant correlation between the relative bone gain and the doses of simvastatin (p = 0.37). The data suggest that relatively lower doses of simvastatin can consistently promote preclinical bone regeneration. However, the interpretation of these data must consider the heterogenicity of the PLGA-scaffolds, the defect anatomy, the observation period, and the evaluation method.
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Finoli, Anthony, Eva Schmelzer, Patrick Over, Ian Nettleship, and Joerg C. Gerlach. "Open-Porous Hydroxyapatite Scaffolds for Three-Dimensional Culture of Human Adult Liver Cells." BioMed Research International 2016 (2016): 1–7. http://dx.doi.org/10.1155/2016/6040146.
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Liver cell culture within three-dimensional structures provides an improved culture system for various applications in basic research, pharmacological screening, and implantable or extracorporeal liver support. Biodegradable calcium-based scaffolds in such systems could enhance liver cell functionality by providing endothelial and hepatic cell support through locally elevated calcium levels, increased surface area for cell attachment, and allowing three-dimensional tissue restructuring. Open-porous hydroxyapatite scaffolds were fabricated and seeded with primary adult human liver cells, which were embedded within or without gels of extracellular matrix protein collagen-1 or hyaluronan. Metabolic functions were assessed after 5, 15, and 28 days. Longer-term cultures exhibited highest cell numbers and liver specific gene expression when cultured on hydroxyapatite scaffolds in collagen-1. Endothelial gene expression was induced in cells cultured on scaffolds without extracellular matrix proteins. Hydroxyapatite induced gene expression for cytokeratin-19 when cells were cultured in collagen-1 gel while culture in hyaluronan increased cytokeratin-19 gene expression independent of the use of scaffold in long-term culture. The implementation of hydroxyapatite composites with extracellular matrices affected liver cell cultures and cell differentiation depending on the type of matrix protein and the presence of a scaffold. The hydroxyapatite scaffolds enable scale-up of hepatic three-dimensional culture models for regenerative medicine applications.
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Nizami, Bilal, Igor V. Tetko, Neil A. Koorbanally, and Bahareh Honarparvar. "QSAR models and scaffold-based analysis of non-nucleoside HIV RT inhibitors." Chemometrics and Intelligent Laboratory Systems 148 (November 2015): 134–44. http://dx.doi.org/10.1016/j.chemolab.2015.09.011.
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Jongpaiboonkit, Leenaporn, C. Y. Lin, P. H. Krebsbach, S. J. Hollister, and J. W. Halloran. "Mechanical Behavior of Complex 3D Calcium Phosphate Cement Scaffolds Fabricated by Indirect Solid Freeform Fabrication In Vivo." Key Engineering Materials 309-311 (May 2006): 957–60. http://dx.doi.org/10.4028/www.scientific.net/kem.309-311.957.
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Calcium phosphate cement is a bioceramic with potential applications for bone-tissue engineering. In this work, controlled porous calcium phosphate scaffolds with interconnected pores were computationally designed by an image-based approach and fabricated by indirect solid freeform fabrication (ISFF) or ‘lost mold’ technique. Voxel finite-element analysis (FEA) showed that mechanical properties of design and fabricated scaffold can be predicted computationally. Scaffolds were then implanted subcutaneously to demonstrate tissue in-growth. Previously, we showed the ability of porous calcium phosphate cement scaffolds to have sufficiently strong mechanical properties for bone tissue engineering applications. This work shows the image-based FEAs from micro-CT scans in vivo (four- and eight weeks). Extensive new bone apposition was noted with micro-CT technique after four- and eight weeks. FEA models of the original design and scaffolds with newly bone formed were compared.
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Carotenuto, Felicia, Noemi Fiaschini, Paolo Di Nardo, and Antonio Rinaldi. "Towards a Material-by-Design Approach to Electrospun Scaffolds for Tissue Engineering Based on Statistical Design of Experiments (DOE)." Materials 16, no. 4 (February 12, 2023): 1539. http://dx.doi.org/10.3390/ma16041539.
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Electrospinning bears great potential for the manufacturing of scaffolds for tissue engineering, consisting of a porous mesh of ultrafine fibers that effectively mimic the extracellular matrix (ECM) and aid in directing stem cell fate. However, for engineering purposes, there is a need to develop material-by-design approaches based on predictive models. In this methodological study, a rational methodology based on statistical design of experiments (DOE) is discussed in detail, yielding heuristic models that capture the linkage between process parameters (Xs) of the electrospinning and scaffold properties (Ys). Five scaffolds made of polycaprolactone are produced according to a 22-factorial combinatorial scheme where two Xs, i.e., flow rate and applied voltage, are varied between two given levels plus a center point. The scaffolds were characterized to measure a set of properties (Ys), i.e., fiber diameter distribution, porosity, wettability, Young’s modulus, and cell adhesion on murine myoblast C1C12 cells. Simple engineering DOE models were obtained for all Ys. Each Y, for example, the biological response, can be used as a driver for the design process, using the process-property model of interest for accurate interpolation within the design domain, enabling a material-by-design strategy and speeding up the product development cycle. The implications are also illustrated in the context of the design of multilayer scaffolds with microstructural gradients and controlled properties of each layer. The possibility of obtaining statistical models correlating between diverse output properties of the scaffolds is highlighted. Noteworthy, the featured DOE approach can be potentially merged with artificial intelligence tools to manage complexity and it is applicable to several fields including 3D printing.
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Satbhaiya, Shruti, and O. P. Chourasia. "Scaffold and cell line based approaches for QSAR studies on anticancer agents." RSC Advances 5, no. 103 (2015): 84810–20. http://dx.doi.org/10.1039/c5ra18295f.
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Yang, Yadong, Geng Yang, Xingzhu Liu, Yimeng Xu, Siyu Zhao, Wenyuan Zhang, and Mengjiao Xu. "Construction of Lung Tumor Model for Drug Screening Based on 3D Bio-Printing Technology." Journal of Biomaterials and Tissue Engineering 11, no. 7 (July 1, 2021): 1213–26. http://dx.doi.org/10.1166/jbt.2021.2706.
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As is known to all, the biological characteristics of two-dimensional (2D) cultured cells are quite different from those in vivo, so the 2D screening model can no longer meet people’s needs. With the development of tissue engineering, people are committed to developing 3D tissue models that can better reflect the biology in vivo, and tend to be mass and miniaturized. In this study, three-dimensional (3D) bio-printing was used to develop an appropriate 3D model for screening sensitive anti-lung cancer drugs in vitro. A549 lung cancer cells were mixed with 8% sodium alginate and 5% gelatin as bio-printing ink to fabricate a cell-laden hydrogel grid scaffold structure. The sensitivity of the printed 3D model to drugs was evaluated with eight anti-tumor traditional Chinese medicines. A fluorescent live/dead staining was carried out at different time to assess the cell survival rate in the 3D scaffolds. MTT assay was used to determine the inhibitory rate of eight antitumor traditional Chinese medicines on A549 cell proliferation in 3D-printed lung tumor models and conventional 2D culture models.
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Newman, Kristen, Kendra Clark, Bhuvaneswari Gurumurthy, Pallabi Pal, and Amol V. Janorkar. "Elastin-Collagen Based Hydrogels as Model Scaffolds to Induce Three-Dimensional Adipocyte Culture from Adipose Derived Stem Cells." Bioengineering 7, no. 3 (September 12, 2020): 110. http://dx.doi.org/10.3390/bioengineering7030110.
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This study aimed to probe the effect of formulation of scaffolds prepared using collagen and elastin-like polypeptide (ELP) and their resulting physico-chemical and mechanical properties on the adipogenic differentiation of human adipose derived stem cells (hASCs). Six different ELP-collagen scaffolds were prepared by varying the collagen concentration (2 and 6 mg/mL), ELP addition (6 mg/mL), or crosslinking of the scaffolds. FTIR spectroscopy indicated secondary bonding interactions between collagen and ELP, while scanning electron microscopy revealed a porous structure for all scaffolds. Increased collagen concentration, ELP addition, and presence of crosslinking decreased swelling ratio and increased elastic modulus and compressive strength of the scaffolds. The scaffold characteristics influenced cell morphology, wherein the hASCs seeded in the softer, non-crosslinked scaffolds displayed a spread morphology. We determined that stiffer and/or crosslinked elastin-collagen based scaffolds constricted the spreading of hASCs, leading to a spheroid morphology and yielded an enhanced adipogenic differentiation as indicated by Oil Red O staining. Overall, this study underscored the importance of spheroid morphology in adipogenic differentiation, which will allow researchers to create more physiologically-relevant three-dimensional, in vitro culture models.
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Pazhanimala, Shaleena K., Driton Vllasaliu, and Bahijja T. Raimi-Abraham. "Engineering Biomimetic Gelatin Based Nanostructures as Synthetic Substrates for Cell Culture." Applied Sciences 9, no. 8 (April 17, 2019): 1583. http://dx.doi.org/10.3390/app9081583.
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There is a need for synthetic substrates that replicate the natural environment for in vitro intestinal models. Electrospinning is one of the most versatile and cost-effective techniques to produce nanofibrous scaffolds mimicking the basement membrane topography. In this study, three different novel electrospun nanofibrous scaffolds made of a polycaprolactone (PCL), gelatin, and poloxamer 188 (P188) blend were produced and compared with PCL and PCL/gelatin fibers produced using the same solvent system and electrospinning parameters. Each polymer solution used in this experiment was electrospun at four different voltages to study its influence on fiber diameter. The morphology and physical characteristics of the fibers were studied using scanning electron microscopy and atomic force microscopy. The average fiber diameter of all scaffolds was within 200–600 nm and no significant decrease in diameter with an increase in voltage was observed. Attenuated total reflection Fourier transform infrared spectroscopy was used to determine the chemical characteristics of the nanofibrous scaffold. The conductivity of the polymer solutions was also analyzed. Biocompatibility of the scaffolds was determined by a cell proliferation study performed using colorectal carcinoma (Caco-2) cells. PCL/gelatin/P188 scaffolds exhibited higher cell proliferation compared to PCL, PCL/gelatin scaffolds, and the control (tissue culture multi-well plate) with PCL/gelatin/P188 80:10:10 sample showing the highest cell proliferation.
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Liu, Wangyu, and Mingke Li. "A new two-step adaptive direct slicing approach for bio-scaffolds in tissue engineering." Rapid Prototyping Journal 23, no. 6 (October 17, 2017): 1170–84. http://dx.doi.org/10.1108/rpj-09-2016-0147.
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Purpose This paper aims to propose the new two-step adaptive direct slicing method for building bio-scaffold with digital micro-mirror device (DMD)-based MPμSLA systems. Design/methodology/approach In this paper, the authors proposed a new approach to directly slice a scaffold’s CAD model (i.e the three-dimensional model built by computer-aided design platforms) and save the slices’ data as BMP (bitmap, i.e. the data format used in DMD) files instead of other types of two-dimensional patterns as an intermediary. The proposed two-step strategy in this paper, i.e. a CAD model’s exterior surface and internal architecture were sliced, respectively, at first, and then assembled together to obtain one intact slice. The assembly process is much easier and convenient based on the slice data in BMP format. To achieve the adaptive slicing for both the exterior part and internal part, two new indices, the exterior surface-dominated index and internal architecture-dominated index, are, respectively, utilized as the error estimation indices. The proposed approach in this paper is developed on SolidWorks platform, but it can also be implemented on other platforms. Findings The authors found that the approach is not only more accurate but also more efficient by avoiding the repeated running of those inefficient rasterization programs. The approach is able to save computer resource and time, and enhance the robustness of slicing program, as well as is appropriate for the scaffolds’ model with internal pore architecture and external free-form surface. Practical implications Bio-scaffolds in tissue engineering require precise control over material distribution, such as the porosity, connectivity, internal pore architecture and external free-form surface. The proposed two-step adaptive direct slicing approach is a good balance of slicing efficiency and accuracy and can be useful for slicing bio-scaffolds’ models. Originality/value This paper gives supports to build bio-scaffold with DMD-based MPμSLA systems.
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Baino, Francesco, Martin Schwentenwein, and Enrica Verné. "Modelling the Mechanical Properties of Hydroxyapatite Scaffolds Produced by Digital Light Processing-Based Vat Photopolymerization." Ceramics 5, no. 3 (September 16, 2022): 593–600. http://dx.doi.org/10.3390/ceramics5030044.
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Porosity is a key feature in dictating the overall performance of biomedical scaffolds, with special relevance to mechanical properties. Usually, compressive strength and elastic modulus are the main parameters used to determine the potential mechanical suitability of porous scaffolds for bone repair. However, their assessment may not be so easy from an experimental viewpoint and, especially if the porosity is high, so reliable for brittle bioceramic foams. Hence, assessing the relationship between porosity and mechanical properties based only on the constitutive parameters of the solid material is a challenging and important task to predict the scaffold performance for optimization during design. In this work, a set of equations was used to predict the compressive strength and elastic modulus of bone-like hydroxyapatite scaffolds produced by digital light processing-based vat photopolymerization (total porosity about 80 vol.%). The compressive strength was found to depend on total porosity, following a power-law approximation. The relationship between porosity and elastic modulus was well fitted by second-order power law, with relative density and computational models obtained by numerical simulations.
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Renno, Giacomo, Francesca Cardano, Giorgio Volpi, Claudia Barolo, Guido Viscardi, and Andrea Fin. "Imidazo[1,5-a]pyridine-Based Fluorescent Probes: A Photophysical Investigation in Liposome Models." Molecules 27, no. 12 (June 16, 2022): 3856. http://dx.doi.org/10.3390/molecules27123856.
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Imidazo[1,5-a]pyridine is a stable scaffold, widely used for the development of emissive compounds in many application fields (e.g., optoelectronics, coordination chemistry, sensors, chemical biology). Their compact shape along with remarkable photophysical properties make them suitable candidates as cell membrane probes. The study of the membrane dynamics, hydration, and fluidity is of importance to monitor the cellular health and to explore crucial biochemical pathways. In this context, five imidazo[1,5-a]pyridine-based fluorophores were synthesized according to a one-pot cyclization between an aromatic ketone and benzaldehyde in the presence of ammonium acetate and acetic acid. The photophysical features of prepared compounds were investigated in several organic solvents and probes 2–4 exhibited the greatest solvatochromic behavior, resulting in a higher suitability as membrane probes. Their interaction with liposomes as artificial membrane model was tested showing a successful intercalation of the probes in the lipid bilayer. Kinetic experiments were carried out and the lipidic phase influence on the photophysical features was evaluated through temperature-dependent experiments. The results herein reported encourage further investigations on the use of imidazo[1,5-a]pyridine scaffold as fluorescent membrane probes.
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BOSCHETTI, FEDERICA, MARGHERITA CIOFFI, MANUELA TERESA RAIMONDI, FRANCESCO MIGLIAVACCA, and GABRIELE DUBINI. "NEW TRENDS IN TISSUE ENGINEERED CARTILAGE: MICROFLUID DYNAMICS IN 3-D ENGINEERED CELL SYSTEMS." Journal of Mechanics in Medicine and Biology 05, no. 03 (September 2005): 455–64. http://dx.doi.org/10.1142/s0219519405001564.
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Bioreactors allowing culture medium direct-perfusion overcome diffusion limitations associated with static culturing and provide flow-mediated mechanical stimuli. The hydrodynamic stress imposed on chondrocytes will depend not only on the culture medium flow rate, but also on the scaffold three-dimensional (3D) micro-architecture. We performed computational fluid-dynamic (CFD) simulations of the flow of culture medium through a 3D porous scaffold, with the aim of predicting the shear stress acting on the cells as a function of parameters that can be set in a tissue-engineering experiment, such as the medium flow rate and the diameter of the perfused scaffold section. We developed two CFD models: the first model (Model 1) was built from micro-computed tomography reconstruction of the actual scaffold geometry, while the second model (Model 2) was based on a simplification of the actual scaffold microstructure. The two models showed comparable results in terms of the distribution of the shear stresses acting on the inner surfaces of the scaffold walls. Models 1 and 2 gave a median shear stress of 3 mPa at a flow rate of 0.5 cm3 min-1 through a 15 mm diameter scaffold. Our results provide a basis for the completion of more exhaustive quantitative studies to further assess the relationship between perfusion at known micro-fluid dynamic conditions and tissue growth in vitro.