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Biomedical subjects

Clemens A van Blitterswijk

Publications and source records attributed to Clemens A van Blitterswijk.

At least 19 recordsLinked to original sources
PubMed2006

Analysis of ectopic and orthotopic bone formation in cell-based tissue-engineered constructs in goats.

Despite decades of extensive research, the application of cell-based bone tissue engineering in clinically relevant models remains challenging. To improve effectiveness, a better understanding of how the technique should work is crucial. In the current study, we investigated the onset time, rate, location and direction of bone formation in ectopically and orthotopically implanted clinically sized tissue-engineered constructs to gain insight the mechanism behind it. Bone marrow stromal cells (BMSCs) were obtained from 10 goats, culture expanded and cryopreserved. Porous biphasic calcium phosphate (BCP) disks of 17mmx6mm were per-operatively seeded with BMSCs or left empty. Both conditions were implanted intramuscularly and in bilateral critical-sized iliac wing defects. Fluorochromes were administered at 3, 5 and 7 weeks and samples were retrieved after 9 weeks. Histology showed abundant and homogeneous bone formation throughout the intramuscular BMSC samples and little bone in the controls. Histomorphometry and measurements of the fluorochrome labels of the ectopical BMSC samples indicated that osteogenesis started at the periphery and subsequent osteoconduction filled the whole scaffold within 7 weeks. In the orthotopically implanted disks, there was good integration with the surrounding bone, but minimal bone in the center of the implants, in both conditions. Bone was only derived from the interface with the surrounding bone, there was no early bone at the surfaces in contact to soft tissue as was seen in the ectopical samples. Apparently cell survival was minimal and insufficient for relevant additional bone formation. However, the speed of integration with surrounding bone and subsequent bone apposition on the BMSC-seeded orthotopic scaffolds were found to be significantly enhanced, which may be relevant especially in challenging environments.

Animals↗
PubMed2006

Polymer hollow fiber three-dimensional matrices with controllable cavity and shell thickness.

Hollow fibers find useful applications in different disciplines like fluid transport and purification, optical guidance, and composite reinforcement. In tissue engineering, they can be used to direct tissue in-growth or to serve as drug delivery depots. The fabrication techniques currently available, however, do not allow to simultaneously organize them into three-dimensional (3D) matrices, thus adding further functionality to approach more complicated or hierarchical structures. We report here the development of a novel technology to fabricate hollow fibers with controllable hollow cavity diameter and shell thickness. By exploiting viscous encapsulation, a rheological phenomenon often undesired in molten polymeric blends flowing through narrow ducts, fibers with a shell-core configuration can be extruded. Hollow fibers are then obtained by selective dissolution of the inner core polymer. The hollow cavity diameter and the shell thickness can be controlled by varying the polymers in the blend, the blend composition, and the extrusion nozzle diameter. Simultaneous with extrusion, the extrudates are organized into 3D matrices with different architectures and custom-made shapes by 3D fiber deposition, a rapid prototyping tool which has recently been applied for the production of scaffolds for tissue engineering purposes. Applications in tissue engineering and controlled drug delivery of these constructs are presented and discussed.

Biocompatible Materials↗
PubMed2006

The effect of cell-based bone tissue engineering in a goat transverse process model.

A disadvantage of traditional posterolateral spinal fusion models is that they are highly inefficient for screening multiple conditions. We developed a multiple-condition model that concentrates on the initial process of bone formation from the transverse process and not on a functional fusion. The effect of bone marrow stromal cells (BMSCs) in four different porous ceramic scaffolds was investigated in this setting. Polyacetal cassettes were designed to fit on the goat transverse process and house four different ceramic blocks, i.e: hydroxyapatite (HA) sintered at 1,150 degrees and 1,250 degrees; biphasic calcium phosphate (BCP) and tricalcium phosphate (TCP). Goat BMSCs (n=10) were cultured and per-operatively seeded autologeously on one of two cassettes implanted per animal. The cassettes were bilaterally mounted on the dorsum of decorticated L2-processes for 9 weeks. To asses the dynamics of bone formation, fluorochrome labels were administered and histomorphometry focused on the distribution of bone in the scaffolds. A clear difference in the extent of bone ingrowth was determined for the different scaffold types. An obvious effect of BMSC seeding was observed in three of four scaffold types, especially in scaffold regions adjacent to the overlying muscle. Generally, the BCP and TCP scaffolds showed better osteoconduction and an increased response to BMSCs administration. In conclusion the model provides a reliable and highly efficient method to study bone formation in cell-based tissue engineering. An effect of cell administration was obvious in three of the four scaffold materials.

Animals↗
PubMed2006

Osteoinduction by biomaterials--physicochemical and structural influences.

Osteoinduction by biomaterials has been shown to be a real phenomenon by many investigators in the last decade. The exact mechanism of this phenomenon is, however, still largely unknown. This in vivo study in goats was performed to get insight into processes governing the phenomenon of osteoinduction by biomaterials and had four main goals: (i) to further investigate the influence of physicochemical properties and structure on biomaterial osteoinductive potential, (ii) to investigate the influence of implant size on the amount of induced bone, (iii) to investigate implantation site dependence, and (iv) to investigate changes occurring on the surface of the material after implantation. Intramuscular implantations of four different biphasic calcium phosphate ceramics, consisting of hydroxyapatite and beta-tricalcium phosphate and a carbonated apatite ceramic, indicated that, for a maximal osteoinductive potential, there is an optimal specific surface area for each material type. It was further shown that a decrease of the implant size with a half significantly decreased the relative amount of induced bone. In addition, subcutaneous implantation did not give rise to ectopic bone formation in any of the animals, while bone was induced in most animals intramuscularly. Analysis of the surfaces of the materials after subcutaneous implantation inside diffusion chambers indicated that the increased specific surface area leads to more surface reactivity, which is hypothesized to be essential for osteoinductivity by biomaterials.

Animals↗
PubMed2006

Fiber diameter and texture of electrospun PEOT/PBT scaffolds influence human mesenchymal stem cell proliferation and morphology, and the release of incorporated compounds.

Electrospinning (ESP) has lately shown a great potential as a novel scaffold fabrication technique for tissue engineering. Scaffolds are produced by spinning a polymeric solution in fibers through a spinneret connected to a high-voltage electric field. The fibers are then collected on a support, where the scaffold is created. Scaffolds can be of different shapes, depending on the collector geometry, and have high porosity and high surface per volume ratio, since the deposited fibers vary from the microscale to the nanoscale range. Such fibers are quite effective in terms of tissue regeneration, as cells can bridge the scaffold pores and fibers, resulting in a fast and homogeneous tissue growth. Furthermore, fibers can display a nanoporous ultrastructure due to solvent evaporation. The aim of this study was to characterize electrospun scaffolds from poly(ethylene oxide terephthalate)-poly(butylene terephthalate) (PEOT/PBT) copolymers and to unravel the mechanism of pore formation on the fibers. The effect of different fiber diameters and of their surface nanotopology on cell seeding, attachment, and proliferation was studied. Smooth fibers with diameter of 10microm were found to support an optimal cell seeding and attachment within the micrometer range analyzed. Moreover, a nanoporous surface significantly enhanced cell proliferation and cells spreading on the fibers. The fabrication of ESP scaffolds with incorporated dyes with different molecular dimensions is also reported and their release measured. These findings contribute to the field of cell-material interaction and lead to the fabrication of "smart" scaffolds which can direct cells morphology and proliferation, and eventually release biological signals to properly conduct tissue formation.

Biocompatible Materials↗
PubMed2006

Evaluation of chondrogenesis within PEGT: PBT scaffolds with high PEG content.

Porous poly(ethylene glycol) terephthalate:poly (butylene terephthalate) (PEGT:PBT) scaffolds with high PEG molecular weight (1000 g/mole) and PEGT content (60%) were fabricated using two different processes-paraffin templating and compression molding-for cartilage engineering applications. This polymer composition has previously been shown to enable chondrocyte adhesion and maintain differentiated phenotype in 2D monolayer culture. The influence of 3D polymer scaffold processing on the formation of cartilaginous tissue was studied by seeding primary immature bovine chondrocytes within cylindrical scaffolds in mixed flask reactors for 3 days, followed by cultivation in culture plates for a total of 10 or 24 days. Tissue-polymer constructs were evaluated morphologically by SEM and histology, and quantitatively for cellularity, total collagen, and glycosaminoglycan content, all of which remained statistically equivalent for each time point tested, irrespective of fabrication method. These data demonstrate that the polymers engineered for this study were able to support chondrogenesis independent of scaffold fabrication process, with the influence of pore architecture lessened by the highly hydrated scaffold microenvironments induced by high PEG content.

Animals↗
PubMed2006

Relevance of osteoinductive biomaterials in critical-sized orthotopic defect.

Several publications have shown the phenomenon of osteoinduction by biomaterials to be real. However, whether the ability of a biomaterial to initiate bone formation in ectopic implantation sites improves the performance of such osteoinductive biomaterial in clinically relevant orthotopic sites remains unclear. No studies have been published in which osteoinductive potential of a biomaterial is directly related to its performance orthotopically. In this study, we compared osteoinductive and nonosteoinductive biphasic calcium-phosphate (BCP) ceramics ectopically and in a clinically relevant critical-sized orthotopic defect in goats. The two materials, BCP1150 and BCP1300, had similar chemical compositions, crystallinities, and macrostructures, but their microstructures differed significantly. BCP1150, sintered at a lower temperature, had a large amount of micropores, small average crystal size, and hence a high specific surface area. In contrast, BCP1300, with few micropores, had a significantly lower specific surface area as compared to BCP1150. Twelve-week intramuscular implantation in goats (n = 10) showed that bone was induced in all BCP1150 implants, while no signs of bone formation were found in any of the BCP1300 implants. After 12 weeks of implantation in a bilateral critical-sized iliac wing defect in the same goats, BCP1150 showed significantly more bone than BCP1300. In addition, the analysis of fluorochrome markers, which were administered to the animals 4, 6, and 8 weeks after implantation to follow the bone growth dynamics, showed an earlier start of bone formation in BCP1150 as compared to BCP1300. Significantly better performance of an osteoinductive ceramic in a critical-sized orthotopic defect in a large animal model in comparison to a nonosteoinductive ceramic suggests osteoinduction to be clinically relevant. Further improvement of material osteoinductive properties is thus a significant step forward in the search for alternatives for autologous bone graft.

Animals↗
PubMed2006

Modulation of chondrocyte phenotype for tissue engineering by designing the biologic-polymer carrier interface.

Therapeutic strategies based on cell and tissue engineering can be advanced by developing material substrates that effectively interrogate the biological compartment, with or without the complimentary local release of growth factors. Poly(ether ester) segmented copolymers were engineered as model material systems to elucidate the interfacial molecular events that govern the function of adhered cells. Surface chemistry was modulated by varying poly(ethylene glycol) (PEG) length and mole fraction with poly(butylene terephthalate) (PBT), leading to differential competitive protein adsorption of fibronectin and vitronectin from serum and consequently to different cell attachment modes. Adhesion within the hydrogel-like milieu of longer surface PEG was mediated via binding to the CD44 transmembrane receptor, rather than the RGD-integrin mechanism, whereas greater substrate-bound fibronectin resulted in cell adhesion via integrins. These adhesion modalities differentially impacted morphological cell phenotype (spread or spheroid) and the subsequent expression of mRNA transcripts (collagen types II, I) characteristic of phenotypically differentiated or dedifferentiated chondrocytes, respectively. These results demonstrate that materials can be designed to directly elicit the membrane bound receptor apparatus desired for downstream cellular response, without requiring exogenous biological growth factors to enable differentiated potential.

Blotting, Western↗
PubMed2006

Cross-species comparison of ectopic bone formation in biphasic calcium phosphate (BCP) and hydroxyapatite (HA) scaffolds.

Material-induced bone formation reported in canine, bovid, suid, and primate species does not often occur in lagomorph or rodent models. In this study, we test biphasic calcium phosphate and hydroxyapatite- induced bone formation in subcutaneous pockets of mice and intramuscular pockets in rats, rabbits, and dogs. All scaffolds are of similar size, and all animals were sacrificed at 90 days post-implantation. In dogs (N = 8), all implants showed bone formation with significantly more bone formed in biphasic calcium phosphates (30 +/- 6%, N = 8) as compared to hydroxyapatite (14 +/- 5%, N = 8) (p = 0.003). Hydroxyapatite implants did not induce bone formation in mice, rats, or rabbits. Biphasic calcium phosphate induced bone in 6 of 8 scaffolds implanted in 4 rabbits and 3 of 16 scaffolds implanted in 16 mice, whereas it did not induce bone formation in any of the 8 rats. The results presented herein suggest that the incidence of material-induced bone formation varies with animal species and is related to the implant material used.

Animals↗
PubMed2006

Differential cell viability of chondrocytes and progenitor cells in tissue-engineered constructs following implantation into osteochondral defects.

Animal studies in cartilage tissue engineering usually include the transfer of cultured cells into chondral or osteochondral defects. Immediately at implantation, the cells are exposed to a dramatically changed environment. The aim of this study was to determine the viability of two cell types currently considered for cellular therapies of cartilage defects-chondrocytes and progenitor cells-shortly after exposure to an osteochondral defect in rabbit knees. To that end, autogenic chondrocytes and periosteal cells were labeled with CM-DiI fluorochrome, seeded or cultured in PEGT/PBT scaffolds for periods up to 2 weeks, transferred into osteochondral defects, harvested 5 days postimplantation, and analyzed for cell viability. In order to further elucidate factors effecting cell viability within our model system, we investigated the effect of serum, 2) extracellular matrix surrounding implanted cells, 3) scaffold interconnectivity, and 4) hyaluronan, as a known cell protectant. Controls included scaffolds with devitalized cells and scaffolds analyzed at implantation. We found that the viability of periosteum cells (14%), but not of chondrocytes (65-95%), was significantly decreased after implantation. The addition of hyaluronan increased periostium cell viability to 44% (p < 0.05). Surprisingly, cell viability in less interconnected compression-molded scaffolds was higher compared to that of fully interconnected scaffolds produced by rapid prototyping. All other factors tested did not affect viability significantly. Our data suggest chondrocytes as a suitable cell source for cartilage repair in line with clinical data on several chondrocyte-based therapies. Although we did not test progenitor cells other the periosteum cells, tissue-engineering approaches using such cell types should take cell viability aspects into consideration.

Animals↗
PubMed2005

Synthetic scaffold morphology controls human dermal connective tissue formation.

Engineering tissues in bioreactors is often hampered by disproportionate tissue formation at the surface of scaffolds. This hinders nutrient flow and retards cell proliferation and tissue formation inside the scaffold. The objective of this study was to optimize scaffold morphology to prevent this from happening and to determine the optimal scaffold geometric values for connective tissue engineering. After comparing lyophilized crosslinked collagen, compression molded/salt leached PEGT/PBT copolymer and collagen-PEGT/PBT hybrid scaffolds, the PEGT/PBT scaffold was selected for optimization. Geometric parameters were determined using SEM, microcomputed tomography, and flow permeability measurements. Fibroblast were seeded and cultured under dynamic flow conditions for 2 weeks. Cell numbers were determined using CyQuant DNA assay, and tissue distribution was visualized in H&E- and Sirius Red-stained sections. Scaffolds 0.5 and 1.5 mm thick showed bridged connected tissue from top-to-bottom, whereas 4-mm-thick scaffolds only revealed tissue ingrowth until a maximum depth of 0.6-0.8 mm. Rapid prototyped scaffold were used to assess the maximal void space (pore size) that still could be filled with tissue. Tissue bridging between fibers was only found at fiber distances < or =401 +/- 60 microm, whereas filling of void spaces in 3D-deposited scaffolds only occurred at distances < or =273 +/- 55 microm. PEGT/PBT scaffolds having similar optimal porosities, but different average interconnected pore sizes of 142 +/- 50, 160 +/- 56 to 191 +/- 69 microm showed comparable seeding efficiencies at day 1, but after 2 weeks the total cell numbers were significantly higher in the scaffolds with intermediate and high interconnectivity. However, only scaffolds with an intermediate interconnectivity revealed homogenous tissue formation throughout the scaffold with complete filling of all pores. In conclusion, significant amount of connective tissue was formed within 14 days using a dynamic culture process that filled all void spaces of a PEGT/PBT scaffolds with the following geometric parameters: thickness 1.5-1.6 mm, pore size range 90-360 microm, and average interconnecting pore size of 160 +/- 56 microm.

Biocompatible Materials↗
PubMed2005

A perfusion bioreactor system capable of producing clinically relevant volumes of tissue-engineered bone: in vivo bone formation showing proof of concept.

In an effort to produce clinically relevant volumes of tissue-engineered bone products, we report a direct perfusion bioreactor system. Goat bone marrow stromal cells (GBMSCs) were dynamically seeded and proliferated in this system in relevant volumes (10 cc) of small sized macroporous biphasic calcium phosphate scaffolds (BCP, 2-6 mm). Cell load and cell distribution were shown using methylene blue block staining and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) staining was used to demonstrate viability of the present cells. After 19 days of cultivation, the scaffolds were covered with a viable, homogeneous cell layer. The hybrid structures became interconnected and a dense layer of extracellular matrix was present as visualized by environmental scanning electron microscopy (ESEM). ESEM images showed within the extracellular matrix sphere like structures which were identified as calcium phosphate nodules by energy dispersive X-ray analysis (EDX). On line oxygen measurements during cultivation were correlated with proliferating GBMSCs. It was shown that the oxygen consumption can be used to estimate GBMSC population doubling times during growth in this bioreactor system. Implantation of hybrid constructs, which were proliferated dynamically, showed bone formation in nude mice after 6 weeks of implantation. On the basis of our results we conclude that a direct perfusion bioreactor system is capable of producing clinically relevant volumes of tissue-engineered bone in a bioreactor system which can be monitored on line during cultivation and show bone formation after implantation in nude mice.

Animals↗
PubMed2005

The regulation of expanded human nasal chondrocyte re-differentiation capacity by substrate composition and gas plasma surface modification.

Optimizing re-differentiation of clinically relevant cell sources on biomaterial substrates in serum containing (S+) and serum-free (SF) media is a key consideration in scaffold-based articular cartilage repair strategies. We investigated whether the adhesion and post-expansion re-differentiation of human chondrocytes could be regulated by controlled changes in substrate surface chemistry and composition in S+ and SF media following gas plasma (GP) treatment. Expanded human nasal chondrocytes were plated on gas plasma treated (GP+) or untreated (GP-) poly(ethylene glycol)-terephthalate-poly(butylene terephthalate) (PEGT/PBT) block co-polymer films with two compositions (low or high PEG content). Total cellularity, cell morphology and immunofluorescent staining of vitronectin (VN) and fibronectin (FN) integrin receptors were evaluated, while post-expansion chondrogenic phenotype was assessed by collagen types I and II mRNA expression. We observed a direct relationship between cellularity, cell morphology and re-differentiation potential. Substrates supporting high cell adhesion and a spread morphology (i.e. GP+ and low PEG content films), resulted in a significantly greater number of cells expressing alpha5beta1 FN to alpha(V)beta3 VN integrin receptors, concomitant with reduced collagen type II/ImRNA gene expression. Substrates supporting low cell adhesion and a spherical morphology (GP- and high PEG content films) promoted chondrocyte re-differentiation indicated by high collagen type II/I gene expression and a low percentage of alpha5beta1 FN integrin expressing cells. This study demonstrates that cell-substrate interactions via alpha5beta1 FN integrin mediated receptors negatively impacts expanded human nasal chondrocyte re-differentiation capacity. GP treatment promotes cell adhesion in S+ media but reverses the ability of low PEG content PEGT/PBT substrates to maintain chondrocyte phenotype. We suggest alternative cell immobilization techniques to GP are necessary for clinical application in articular cartilage repair.

Adult↗
PubMed2005

A new in vivo screening model for posterior spinal bone formation: comparison of ten calcium phosphate ceramic material treatments.

This study presents a new screening model for evaluating the influence of multiple conditions on the initial process of bone formation in the posterior lumbar spine of a large animal. This model uses cages designed for placement on the decorticated transverse process of the goat lumbar spine. Five conduction channels per cage, each be defined by a different material treatment, are open to both the underlying bone and overlying soft tissue. The model was validated in ten adult Dutch milk goats, with each animal implanted with two cages containing a total of ten calcium phosphate material treatments according to a randomized complete block design. The ten calcium phosphate ceramic materials were created through a combination of material chemistry (BCP, TCP, HA), sintering temperature (low, medium, high), calcination and surface roughness treatments. To monitor the bone formation over time, fluorochrome markers were administered at 3, 5 and 7 weeks and the animals were sacrificed at 9 weeks after implantation. Bone formation in the conduction channels was investigated by histology and histomorphometry of non-decalcified sections using traditional light and epifluorescent microscopy. According to both observed and measured bone formation parameters, materials were ranked in order of increasing magnitude as follows: low sintering temperature BCP (rough and smooth) approximately medium sintering temperature BCP approximately = TCP > calcined low sintering temperature HA > non-calcined low sintering temperature HA > high sintering temperature BCP (rough and smooth) > high sintering temperature HA (calcined and non-calcined). These results agree closely with those obtained in previous studies of osteoconduction and bioactivity of ceramics thereby validating the screening model presented in this study.

Animals↗
PubMed2005

Engineering vascularized skeletal muscle tissue.

One of the major obstacles in engineering thick, complex tissues such as muscle is the need to vascularize the tissue in vitro. Vascularization in vitro could maintain cell viability during tissue growth, induce structural organization and promote vascularization upon implantation. Here we describe the induction of endothelial vessel networks in engineered skeletal muscle tissue constructs using a three-dimensional multiculture system consisting of myoblasts, embryonic fibroblasts and endothelial cells coseeded on highly porous, biodegradable polymer scaffolds. Analysis of the conditions for induction and stabilization of the vessels in vitro showed that addition of embryonic fibroblasts increased the levels of vascular endothelial growth factor expression in the construct and promoted formation and stabilization of the endothelial vessels. We studied the survival and vascularization of the engineered muscle implants in vivo in three different models. Prevascularization improved the vascularization, blood perfusion and survival of the muscle tissue constructs after transplantation.

Animals↗
PubMed2005

Biological performance of uncoated and octacalcium phosphate-coated Ti6Al4V.

The in vivo behavior of a porous Ti6Al4V material that was produced by a positive replica technique, with and without an octacalcium phosphate (OCP) coating, has been studied both in the back muscle and femur of goats. Macro- and microporous biphasic calcium phosphate (BCP) ceramic, known to be both osteoconductive and able to induce ectopic bone formation, was used for comparison purpose. The three groups of materials (Ti6Al4V, OCP Ti6Al4V and BCP) were implanted transcortically and intramuscularly for 6 and 12 weeks in 10 adult Dutch milk goats in order to study their osteointegration and osteoinductive potential. In femoral defects, both OCP Ti6Al4V and BCP were performing better than the uncoated Ti6Al4V, at both time points. BCP showed a higher bone amount than OCP Ti6Al4V after 6 weeks of implantation, while after 12 weeks, this difference was no longer significant. Ectopic bone formation was found in both OCP Ti6Al4V and BCP implants after 6 and 12 weeks. The quantity of ectopically formed bone was limited as was the amount of animals in which the bone was observed. Ectopic bone formation was not found in uncoated titanium alloy implants, suggesting that the presence of calcium phosphate (CaP) is important for bone induction. This study showed that CaPs in the form of coating on metal implants or in the form of bulk ceramic have a significantly positive effect on the bone healing process.

Alloys↗
PubMed2005

Effects of scaffold composition and architecture on human nasal chondrocyte redifferentiation and cartilaginous matrix deposition.

We investigated whether the post-expansion redifferentiation and cartilage tissue formation capacity of adult human nasal chondrocytes can be regulated by controlled modifications of scaffold composition and architecture. As a model system, we used poly(ethylene glycol)-terephthalate-poly(butylene)-terephthalate block copolymer scaffolds from two compositions (low or high PEG content, resulting in different wettability) and two architectures (generated by compression molding or three-dimensional (3D) fiber deposition) with similar porosity and mechanical properties, but different interconnecting pore architectures. Scaffolds were seeded with expanded human chondrocytes and the resulting constructs assessed immunohistochemically, biochemically and at the mRNA expression level following up to 4 weeks of static culture. For a given 3D architecture, the more hydrophilic scaffold enhanced cell redifferentiation and cartilaginous tissue formation after 4 weeks culture, as assessed by higher mRNA expression of collagen type II, increased deposition of glycosaminoglycan (GAG) and predominance of type II over type I collagen immunostain. The fiber-deposited scaffolds, with a more accessible pore volume and larger interconnecting pores, supported increased GAG deposition, but only if a more hydrophilic composition was used. By applying controlled and selective modifications of chemico-physical scaffold parameters, we demonstrate that both scaffold composition and architecture are instructive for expanded human chondrocytes in the generation of 3D cartilaginous tissues. The observed effects of composition and architecture were likely to have been mediated, respectively, by differential serum protein adsorption and efficiency of nutrient/waste exchange.

Absorbable Implants↗