Academic literature on the topic 'Scaffold-host integration'

When using heterogeneous extracellular matrix (ECM) derived scaffolds for soft tissue repair, current methods of in vivo evaluation can fail to provide a clear distinction between host collagen and implanted scaffolds making it difficult to assess host tissue integration and remodeling. The purpose of this study is both to evaluate novel scaffolds conjugated with nanoparticles for host tissue integration and biocompatibility and to assess green fluorescent protein (GFP) expressing swine as a new animal model to evaluate soft tissue repair materials. Human-derived graft materials conjugated with nanoparticles were subcutaneously implanted into GFP expressing swine to be evaluated for biocompatibility and tissue integration through histological scoring and confocal imaging. Histological scoring indicates biocompatibility and remodeling of the scaffolds with and without nanoparticles at 1, 3, and 6 months. Confocal microscope images display host tissue integration into scaffolds although nonspecificity of GFP does not allow for quantification of integration. However, the confocal images do allow for spatial observation of host tissue migration into the scaffolds at different depths of penetration. The study concludes that the nanoparticle scaffolds are biocompatible and promote integration and that the use of GFP expressing swine can aid in visualizing the scaffold/host interface and host cell/tissue migration.

A microfibrous tubular scaffold has been designed and fabricated by electrospinning using poly (1,4-butylene succinate) as biocompatible and biodegradable material. The scaffold morphology was optimized as a small diameter and micro-porous conduit, able to foster cell integration, adhesion, and growth while avoiding cell infiltration through the graft’s wall. Scaffold morphology and mechanical properties were explored and compared to those of native conduits. Scaffolds were then seeded with adult normal human dermal fibroblasts to evaluate cytocompatibility in vitro. Haemolytic effect was evaluated upon incubation with diluted whole blood. The scaffold showed no delamination, and mechanical properties were in the physiological range for tubular conduits: elastic modulus (17.5 ± 1.6 MPa), ultimate tensile stress (3.95 ± 0.17 MPa), strain to failure (57 ± 4.5%) and suture retention force (2.65 ± 0.32 N). The shown degradation profile allows the graft to provide initial mechanical support and functionality while being colonized and then replaced by the host cells. This combination of features might represent a step toward future research on PBS as a biomaterial to produce scaffolds that provide structure and function over time and support host cell remodelling.

(1) Background: Developing a high-quality, injectable biomaterial that is labor-saving, cost-efficient, and patient-ready is highly desirable. Our research group has previously developed a collagen-based injectable scaffold for the treatment of a variety of wounds including wounds with deep and irregular beds. Here, we investigated the biocompatibility of our liquid scaffold in mice and compared the results to a commercially available injectable granular collagen-based product. (2) Methods: Scaffolds were applied in sub-dermal pockets on the dorsum of mice. To examine the interaction between the scaffolds and the host tissue, samples were harvested after 1 and 2 weeks and stained for collagen content using Masson’s Trichrome staining. Immunofluorescence staining and quantification were performed to assess the type and number of cells infiltrating each scaffold. (3) Results: Histological evaluation after 1 and 2 weeks demonstrated early and efficient integration of our liquid scaffold with no evident adverse foreign body reaction. This rapid incorporation was accompanied by significant cellular infiltration of stromal and immune cells into the scaffold when compared to the commercial product (p < 0.01) and the control group (p < 0.05). Contrarily, the commercial scaffold induced a foreign body reaction as it was surrounded by a capsule-like, dense cellular layer during the 2-week period, resulting in delayed integration and hampered cellular infiltration. (4) Conclusion: Results obtained from this study demonstrate the potential use of our liquid scaffold as an advanced injectable wound matrix for the management of skin wounds with complex geometries.

Background. To develop an effective surgical procedure for cellular scaffold epiretinal implantation in rhesus, facilitating subsequent epiretinal stem cell transplantation. Methods. Retinal progenitors were seeded onto a poly(lactic-co-glycolic) acid (PLGA) scaffold. First, the cellular scaffolds were delivered by 18G catheter or retinal forceps into rabbit epiretinal space (n=50). Then, the cell survival rate was evaluated by Cell Counting Kit-8 (CCK-8). Second, three methods of scaffold fixation, including adhesion after gas-liquid exchange (n=1), tamponade by hydrogel (n=1), and fixation by retinal tacks (n=4), were performed in rhesus monkeys. After one month, fundus photography and SD-OCT were performed to assess the outcomes, and histological examination was performed to evaluate proliferation. Results. The cell survival rate was significantly higher in the catheter group. Follow-up examination showed that retinal tack fixation was the only method to maintain the scaffolds attached to host retina for at least 3 weeks, which is the minimal time required for cell integration. Histological staining demonstrated slight glial fibrillary acidic protein (GFAP) accumulation in the retinal tack insertion area. Conclusions. The established surgical procedure offers a new insight into research of epiretinal cell replacement therapy in rhesus eyes. The successful delivery and long-term fixation provide a prerequisite for cell migration and integration.

Due to its intrinsically poor repair potential, injuries to articular cartilage do not heal and clinical intervention is required. Osteochondral grafts may improve healing while promoting integration with host tissue. We report here the development of an osteochondral graft based on a hybrid of a hyrogel and a polymer-bioactive glass composite (PLAGA-BG) microsphere scaffold. This novel osteochondral construct consists of three regions: gel-only, gel/composite interface, and a composite-only-region. The three phases differ in calcium phospate (Ca-P) or BG content. The objective of the current study is to investigate the effects of scaffold composition on chondrocyte response, and to evaluate the effects of co-culture on osteoblasts and chondrocyte growh and differentiation on the hybrid scaffold. The PLAGA-BG microsphere scaffold supported the growth of chondrocytes and initial results indicate that in the presence of BG, chondrocyte-mediated mineralization may be stimulated. Co-culture of osteoblasts and chondrocytes on the multi-phased scaffold with varied Ca-P content facilitated the formation of multiple matrix zones: a GAGrich chondrocyte region, an interfacial matrix rich in GAG+collagen, and a mineralized collagen matrix with osteoblasts. In summary, chondrocyte response has been optimized as a function of scaffold composition and the novel osteochondral graft has the potential to support the simultaneous formation of multiple types of tissue in vitro.

Vertical bone augmentation to create host bone prior to implant placement is one of the most challenging regenerative procedures. The objective of this study is to evaluate the capacity of a UV-photofunctionalized titanium microfiber scaffold to recruit osteoblasts, generate intra-scaffold bone, and integrate with host bone in a vertical augmentation model with unidirectional, limited blood supply. Scaffolds were fabricated by molding and sintering grade 1 commercially pure titanium microfibers (20 μm diameter) and treated with UVC light (200–280 nm wavelength) emitted from a low-pressure mercury lamp for 20 min immediately before experiments. The scaffolds had an even and dense fiber network with 87% porosity and 20–50 mm inter-fiber distance. Surface carbon reduced from 30% on untreated scaffold to 10% after UV treatment, which corresponded to hydro-repellent to superhydrophilic conversion. Vertical infiltration testing revealed that UV-treated scaffolds absorbed 4-, 14-, and 15-times more blood, water, and glycerol than untreated scaffolds, respectively. In vitro, four-times more osteoblasts attached to UV-treated scaffolds than untreated scaffolds three hours after seeding. On day 2, there were 70% more osteoblasts on UV-treated scaffolds. Fluorescent microscopy visualized confluent osteoblasts on UV-treated microfibers two days after seeding but sparse and separated cells on untreated microfibers. Alkaline phosphatase activity and osteocalcin gene expression were significantly greater in osteoblasts grown on UV-treated microfiber scaffolds. In an in vivo model of vertical augmentation on rat femoral cortical bone, the interfacial strength between innate cortical bone and UV-treated microfiber scaffold after two weeks of healing was double that observed between bone and untreated scaffold. Morphological and chemical analysis confirmed seamless integration of the innate cortical and regenerated bone within microfiber networks for UV-treated scaffolds. These results indicate synergy between titanium microfiber scaffolds and UV photofunctionalization to provide a novel and effective strategy for vertical bone augmentation.

Numerous intervention strategies have been developed to promote functional tissue repair following experimental spinal cord injury (SCI), including the bridging of lesion-induced cystic cavities with bioengineered scaffolds. Integration between such implanted scaffolds and the lesioned host spinal cord is critical for supporting regenerative growth, but only moderate-to-low degrees of success have been reported. Light and electron microscopy were employed to better characterise the fibroadhesive scarring process taking place after implantation of a longitudinally microstructured type-I collagen scaffold into unilateral mid-cervical resection injuries of the adult rat spinal cord. At long survival times (10 weeks post-surgery), sheets of tightly packed cells (of uniform morphology) could be seen lining the inner surface of the repaired dura mater of lesion-only control animals, as well as forming a barrier along the implant–host interface of the scaffold-implanted animals. The highly uniform ultrastructural features of these scarring cells and their anatomical continuity with the local, reactive spinal nerve roots strongly suggest their identity to be perineurial-like cells. This novel aspect of the cellular composition of reactive spinal cord tissue highlights the increasingly complex nature of fibroadhesive scarring involved in traumatic injury, and particularly in response to the implantation of bioengineered collagen scaffolds.

Most infants with long-gap esophageal atresia receive an esophageal replacement with tissue from stomach or colon, because the native esophagus is too short for true primary repair. Tissue-engineered esophageal conducts could present an attractive alternative. In this paper, circular decellularized porcine esophageal scaffold tissues were implanted subcutaneously into Sprague-Dawley rats. Depending on scaffold cross-linking with genipin, glutaraldehyde, and carbodiimide (untreated scaffolds : positive control; bovine pericardium : gold standard), the number of infiltrating fibroblasts, lymphocytes, macrophages, giant cells, and capillaries was determined to quantify the host response after 1, 9, and 30 days. Decellularized esophagus scaffolds were shown to maintain native matrix morphology and extracellular matrix composition. Typical inflammatory reactions were observed in all implants; however, the cellular infiltration was reduced in the genipin group. We conclude that genipin is the most efficient and best tolerated cross-linking agent to attenuate inflammation and to improve the integration of esophageal scaffolds into its surrounding tissue after implantation.

Over the last two decades, the philosophy behind an optimal fixation of orthopaedic implants progressively evolved towards “bone-conservative” solutions and, accordingly, the researchers’ attention moved from simple mechanical fixation of the prosthesis to host bone by using screws or acrylic cement to new strategies based on a physico-chemical bond (surface modification) in order to minimize bone resection/loss and maximize tissue-implant integration. This research work explores the feasibility of a novel bioceramic single-piece acetabular cup for hip joint prosthesis that can be anchored to the patient’s pelvic bone by means of a bone-like trabecular coating (scaffold) able to promote implant osteointegration.

2005/2006
Tissue loss or end-stage organ failure caused by injury or other types of damage is one of the most devastating and costly problems in human health care. Although surgical strategies have been developed to deal with these problems, and significant advances have been achieved in organ transplantation, it is extremely limited by a critical donor shortage and the necessity of lifelong immunosuppression and its serious complications. In the USA, more than 6,000 people die each year as a result of shortage of donor organs. Tissue engineering [TE] is seen by many as the only way to address this shortage. TE is an interdisciplinary field that draws from materials science, cell biology, biotechnology and chemistry, and strives to offer a new solution to tissue loss or organ failure through the use of synthetic, hybrid, or natural materials that have been designed and fabricated into a 3-dimensional scaffolds that provide support and allow cell attachment, proliferation, differentiation and function. However, Skin and cartilage are the only two tissues grown under laboratory conditions that have achieved successful clinical application. The main reason for this is that cartilage doesn’t require blood vessels or nerves and skin is sustained by nutrients that diffuse through the thickness of the cells that make up the graft. Attempts to grow more biologically challenging tissue and organs have been had mixed results. The obstacles and challenges that have to be overcome include: 1. Graft loss/failure due to at the cyto-incompatibility at the graft-biomaterial interface and bio-incompatibility host-biomaterial interface. 2. Inadequate neovascularization and nutrient channels to support cell survival deep in the interior of the scaffolds. 3. Immuno-rejection of allogenic graft. 4. Lack of healthy easily accessible cells for use in tissue engineering To this end we have developed “smart” biomaterials with nano-scale architecture to elicit desirable cell response (cytocompatibility) at the cell-biomaterial interface and desirable host response (biocompatibility) at the host biomaterial interface. We then designed and microfabricated an original scaffold that incorporated the “smart” architecture and microfluidic network to permit the flow of nutrient-rich media deep in the interior. The scaffold consists of two microporous hemi-membranes that are superimposed and aligned in such a way that the micropores are laterally offset. Sandwiched between these hemi-membranes is a microfluidic channel network that runs perpendicular to the micropore axis and permits interconnectivity between the laterally offset micropores. By decreasing the size of the channels from the micro- to the nano- scale the scaffold acquires a another “smart” characteristic as a immuno-isolating membrane. To examine the scaffold’s potential for tissue regeneration, muscle myoblast cells (mouse C2C12 cell-line), neuroblastomas (mouse PC12 cell-line) and embryonic stem cells (mouse TBV-2 cell-line) were seeded and cultured on the scaffolds. Biocompatibility was evaluated by subcutaneous implantation of the scaffold in mice. Results show that myoblast and neuroblastomas attached, proliferated and differentiated. The exponential cell proliferation associated with in vitro embryonic stem cell culture was controlled. In vivo studies demonstrated scaffold-host integration as evidenced by vascular colonisation of the scaffold.. By developing the ability to construct and control the following scaffold parameters; microporous architecture; microfluidic interconnectivity and canal size; the external and internal shape of the scaffold and it’s multi-scaled surface architectures, the “smart” scaffold developed in our laboratories have great potential as an ideal scaffold for tissue engineering.
Nella cura del benessere degli uomini, tra i problemi di maggior impatto e costo si trovano la perdita di tessuti e di funzionalità degli organi, causati da ferite o incidenti di altro genere. Sebbene siano state sviluppate efficaci strategie chirurgiche per ovviare a tali problemi, e nonostante i significativi avanzamenti tecnici raggiunti nel campo del trapianto degli organi, il ricorso a tale soluzione è fortemente limitato dal basso numero di donatori di organi e dalla necessità di durature terapie immuno-soppressive, con il loro portato di serie complicazioni. Basti pensare che a causa della mancanza di un adeguato numero di donatori, solo negli USA ogni anno muoiono più di 6000 persone. Secondo il parere di molti, la strada più promettente per affrontare questo problema è la Ingegneria dei Tessuti Biologici (ovvero Tissue Engineering [TE], dall’acronimo dell’equivalente inglese). Si tratta di un approccio interdisciplinare, che combinando conoscenze e tecnologie dai campi della Scienza dei Materiali, Biologia Cellulare, Biotecnologia e Chimica offre la possibilità, in principio, di trovare soluzioni innovative per la sostituzione di tessuti o organi non più funzionali; la strada maestra in questo campo è la progettazione e costruzione di strutture tri-dimensionali (scaffold) capaci di provvedere al supporto funzionale di cellule cresciute in vitro, integrando materiali sintetici, naturali e ibridi. Tuttavia, al momento soltanto pelle e cartilagini sono state cresciute in condizioni controllate da laboratorio e hanno raggiunto lo stadio della applicazione clinica. Il motivo fondamentale per tale successo, e per la limitazione a questi due soli casi, è che la cartilagine non necessita di vascolarizzazione o innervazione per sostentarsi, e la pelle ottiene i suoi nutrienti per mezzo della diffusione attraverso gli strati di cellule che la sostengono e ne garantiscono l’attecchimento. Tentativi per crescere altri tipi di tessuti e organi hanno incontrato gravi difficoltà; 1. perdita di adesione a causa della cito-incompatibilità all’interfaccia di connessione e della bio-incompatibilità tra i materiali dell’impianto e il corpo ospitante 2. scarsa o inadeguata vascolarizzazione dell’impianto, tale per cui le cellule all’interno della struttura 3-D non vengono raggiunte dai nutrienti necessari per una sopravvivenza a lungo termine 3. rigetto immunologico del tessuto trapianto 4. mancanza di facile accesso alle cellule necessarie per la costruzione degli impianti Con lo scopo di rispondere a queste richieste, abbiamo sviluppato bio-materiali “smart” contraddistinti da una architettura a livello nano-metrico, capaci di stimolare la desiderata risposta cellulare (compatibilità citologica) all’interfaccia con il bio-materiale stesso, e capace di promuovere la bio-compatibilità con il corpo ospitante. Usando le tecniche della micro-fabbricazione, abbiamo quindi progettato e realizzato una struttura 3-D originale (lo scaffold) che incorpora tale architettura “smart” e il sistema micro-fluidico che garantisce l’apporto del flusso dei nutrienti al suo interno. Tale struttura consiste da membrane sovrapposte ed allineate in modo che lateralmente si aprano dei pori di comunicazione con dimensioni micrometriche. Compreso tra queste membrane si trova il sistema microfluidico, capace di garantire l’interconnessione trai pori con un sistema di canali che scorre perpendicolarmente all’asse dei pori stessi. Una ulteriore caratteristica di questo sistema è che riducendo la scala dei canali microfluidici al livello di scala nano-metrica, lo “scaffold” acquisisce proprietà immuno-isolanti. Per lo studio della sue potenzialità nel campo della rigenerazione tissutale, abbiamo cresciuto nello “scaffold” mioblasti muscolari (linea cellulare C2C12 del topo), neuroblastomi (linea cellulare PC12 del topo) e cellule staminali embrionali (TBV-2 del topo). La biocompatibilità è stata valutata impiantando lo “scaffold” in topi da laboratorio. I risultati mostrano come i mioblastomi e i neuroblastomi aderiscono allo “scaffold”, proliferano e si differenziano. Abbiamo controllato la proliferazione esponenziale associata con la cultura in vitro delle cellule staminali embrionali e lo studio delle condizioni in vivo dimostra la integrazione dello “scaffold” nel corpo dell’ospite, come risultato della riuscita vascolarizzazione della sua struttura. Con il controllo della architettura micro-porosa; interconnettività microfluidica e dimensione dei canali; della geometria esterna ed interna e della sua struttura e conformazione superficiale a scala nano-metrica, lo “scaffold” risultante, sviluppato nei nostri laboratori, mostra enormi potenzialità come struttura ideale per la Ingegneria dei Tessuti Biologici.
XIX Ciclo
1967

High-aspect-ratio three-dimensional structures using biocompatible materials are critical for tissue engineering applications. This study develops a multi-nozzle direct-write approach to construct tissue engineering scaffolds with complex three-dimensional structures utilizing polymeric materials. This approach provides the capability to fabricate three dimensional scaffolds by depositing biocompatible UV-curable polymeric material and thermoplastic material (paraffin wax) layer-by-layer, which respectively are used as structural material and supporting material that will be removed later on. The designed structure is built by selectively extruding drops and/or filament through a set of syringes that host different functional materials, following a layer-by-layer sequence. The location of the deposition is precisely controlled by a high precision three-dimensional translational stage. After different structural/functional materials and the supporting material are deposited with predesigned pattern, the supporting material is removed by using appropriate chemical solvent which will not affect physical and chemical properties of the designed structure. The mechanical property of the structure, the equilibrium modulus and dynamic stiffness, can be engineered by designing different pore size for the scaffold. The multi-nozzle based direct writing approach provides a practical solution to build scaffolds for tissue engineering and integrate multiple functional materials together into a single scaffold structure.

Vascularization of a tissue-engineered construct enables efficient transport of nutrients and waste products; it is necessary for successful long-term tissue growth and host integration. Although significant progress has been made, sufficient vascularization of engineered constructs is still a major challenge, limiting clinical applications of tissue engineering (TE) approaches [1]. Successful vascularization promotes the interactions of TE implants with host tissues, leading to efficient tissue regeneration. Therefore, there is an unmet need to develop a more efficient method to vascularize TE constructs. In particular, obtaining a reliable source of endothelial cells (ECs) that line all blood vessels is a critical and challenging step towards successful vascularization of TE constructs, empowering TE to be applied in a larger scale and scope.