Scaffolds For Cartilage Tissue Engineering Research Articles

Fibrin-Genipin Hydrogel for Cartilage Tissue Engineering in Nasal Reconstruction.

Nasal reconstruction is limited by the availability of autologous cartilage. The aim is to investigate an adhesive biomaterial for tissue engineering of nasal cartilage by evaluating mechanical properties of hydrogels made of fibrin crosslinked with genipin as compared to native tissue. Hydrogels of fibrin, fibrin-genipin, and fibrin-genipin with extracellular matrix (ECM) particles were created and evaluated with mechanical testing to determine compression, tensile, and shear properties. Rabbit nasal septal cartilage was harvested and tested in these modalities for comparison. Transmission electron microscopy characterized hydrogel structure. Fibrin-genipin gels had higher compressive, tensile, and shear moduli compared to fibrin alone or fibrin-genipin with ECM. However, all hydrogel formulations had lower moduli than the rabbit nasal septal cartilage. Electron microscopy showed genipin crosslinking increased structural density of the hydrogel and that cartilage ECM created larger structural features with lower crosslinking density. The addition of genipin significantly improved mechanical properties of fibrin hydrogels by increasing the compressive, tensile, and shear moduli. The addition of cartilage ECM, which can add native structure and composition, resulted in decreased moduli values. Fibrin-genipin is a bioactive and biomechanically stable hydrogel that may offer promise as a scaffold for cartilage tissue engineering in nasal reconstruction, yet further augmentation is required to match material properties of native nasal cartilage.

Thermosensitive Hydrogels as Scaffolds for Cartilage Tissue Engineering.

Articular cartilage defects, caused by trauma, osteoarthritis, or other diseases, always lead to severe joint pain and joint dysfunction. Without access to progenitor cells and the supply of blood and nutrients, the impaired articular cartilage would be short of the capability to self-repair. Although the present clinical treatments, including autogenous and allograft osteochondral transplantation, microfracture technique, and so forth, have shown some efficacies, their drawbacks, such as donor insufficiency and poor-integration with adjacent tissue, limit the satisfactory repair of articular cartilage defects and cause unsatisfied prognosis. Cartilage tissue engineering, involving the combination of progenitor cells with scaffolds, which serve as artificial extracellular matrices (ECMs), provides a promising strategy for cartilage regeneration. Recently, thermosensitive hydrogels have attracted much attention as scaffolds for cartilage tissue engineering owing to their unique physical properties analogous to the native ECM. In this review, we summarize the fabrication, characterization of newly reported thermosensitive hydrogels as cartilage tissue engineering scaffolds. The potential challenges and future perspectives are proposed.

Hypoxia impacts human MSC response to substrate stiffness during chondrogenic differentiation

Tissue engineering strategies often aim to direct tissue formation by mimicking conditions progenitor cells experience within native tissues. For example, to create cartilage in vitro, researchers often aim to replicate the biochemical and mechanical milieu cells experience during cartilage formation in the developing limb bud. This includes stimulating progenitors with TGF-β1/3, culturing under hypoxic conditions, and regulating mechanosensory pathways using biomaterials that control substrate stiffness and/or cell shape. However, as progenitors differentiate down the chondrogenic lineage, the pathways that regulate their responses to mechanotransduction, hypoxia and TGF-β may not act independently, but rather also impact one another, influencing overall cell response. Here, to better understand hypoxia’s influence on mechanoregulatory-mediated chondrogenesis, we cultured human marrow stromal/mesenchymal stem cells (hMSC) on soft (0.167 kPa) or stiff (49.6 kPa) polyacrylamide hydrogels in chondrogenic medium containing TGF-β3. We then compared cell morphology, phosphorylated myosin light chain 2 staining, and chondrogenic gene expression under normoxic and hypoxic conditions, in the presence and absence of pharmacological inhibition of cytoskeletal tension. We show that on soft compared to stiff substrates, hypoxia prompts hMSC to adopt more spread morphologies, assemble in compact mesenchymal condensation-like colonies, and upregulate NCAM expression, and that inhibition of cytoskeletal tension negates hypoxia-mediated upregulation of molecular markers of chondrogenesis, including COL2A1 and SOX9. Taken together, our findings support a role for hypoxia in regulating hMSC morphology, cytoskeletal tension and chondrogenesis, and that hypoxia’s effects are modulated, at least in part, by mechanosensitive pathways. Our insights into how hypoxia impacts mechanoregulation of chondrogenesis in hMSC may improve strategies to develop tissue engineered cartilage. Statement of SignificanceCartilage tissue engineering strategies often aim to drive progenitor cell differentiation by replicating the local environment of the native tissue, including by regulating oxygen concentration and mechanical stiffness. However, the pathways that regulate cellular responses to mechanotransduction and hypoxia may not act independently, but rather also impact one another. Here, we show that on soft, but not stiff surfaces, hypoxia impacts human MSC (hMSC) morphology and colony formation, and inhibition of cytoskeletal tension negates the hypoxia-mediated upregulation of molecular markers of chondrogenesis. These observations suggest that hypoxia’s effects during hMSC chondrogenesis are modulated, at least in part, by mechanosensitive pathways, and may impact strategies to develop scaffolds for cartilage tissue engineering, as hypoxia’s chondrogenic effects may be enhanced on soft materials.

Graphene oxide containing chitosan scaffolds for cartilage tissue engineering

Enhancement of physical and mechanical properties of the scaffolds is achieved via various methods including cross-linking and incorporation of nano particles. In the present research chitosan-based scaffolds firstly were reinforced with the incorporation of the graphene oxide (GO) nanoparticles. The GO nanoparticles were synthesized from graphite successfully and were identified by TGA, XRD, SEM and FTIR analytical methods. Nanocomposite scaffolds based on chitosan with different percentages of the GO were prepared. The chitosan–GO nanocomposite scaffolds were then simultaneously sterilized and cross-linked in an autoclave and comprehensively characterized. In XRD measurements, the absence of the peak at 10° related to GO, is evidence that the GO layers are exfoliated. With increasing the GO concentration from 0 to 0.1, 0.2 and 0.3%, physical and mechanical properties were improved, considerably. Seeding of the human articular chondrocytes on the nanocomposite scaffolds showed an increased proliferation with augmentation of the GO percentage particularly in prolonged cultivation periods (14 days). Investigation of the human articular chondrocyte morphology revealed a more spherical morphology of the cells on the cross-linked scaffolds for 21 days of culture in vitro.

Development and Characterization of Collagen Composite Scaffold for Cartilage Tissue Engineering

Development and Characterization of Collagen Composite Scaffold for Cartilage Tissue Engineering

Evaluation of Mechanical Properties and Cell Viability of Poly (3-Hydroxybutyrate)-Chitosan/Al2O3 Nanocomposite Scaffold for Cartilage Tissue Engineering.

Background:The aim of this study was to evaluate the effects of alumina nanowires as reinforcement phases in polyhydroxybutyrate-chitosan (PHB-CTS) scaffolds to apply in cartilage tissue engineering.Methods:A certain proportion of polymers and alumina was chosen. After optimization of electrospun parameters, PHB, PHB-CTS, and PHB-CTS/3% Al2O3 nanocomposite scaffolds were randomly electrospun. Scanning electron microscopy, Fourier transform infrared spectroscopy, water contact angle measurement, tensile strength, and chondrocyte cell culture studies were used to evaluate the physical, mechanical, and biological properties of the scaffolds.Results:The average fiber diameter of scaffolds was 300–550 nm and the porosity percentages for the first layer of all types of scaffolds were more than 81%. Scaffolds' hydrophilicity was increased by adding alumina and CTS. The tensile strength of scaffolds decreased by adding CTS and increased up to more than 10 folds after adding alumina. Chondrocyte viability and proliferation on scaffolds were better after adding CTS and alumina to PHB.Conclusion:With regard to the results, electrospun PHB-CTS/3% Al2O3 scaffold has the appropriate potential to apply in cartilage tissue engineering.

Stiff micelle-crosslinked hyaluronate hydrogels with low swelling for potential cartilage repair.

Pluronic F127 diacrylate (F127DA) nano-micelle crosslinked methacrylated hyaluronic acid (MeHA) hydrogels (NMgels) with strong compressive properties have been demonstrated in our previous study. The current study further focuses on how the F127DA micelles and long-term swelling affect the mechanical performance of hydrogels from the view of in vitro/in vivo applications. Co-contributions of the F127DA micelles and MeHA to the compression performance are first investigated through mechanical analysis and cyclic loading/unloading tests before and after swelling. The optimized NMgel with F127DA micelles of 15 wt% and MeHA of 1.5 wt% (F15H1.5) exhibits a low swelling ratio and a well-maintained network in pH = 7.4 phosphate buffered saline. The abundant hydration significantly affects the initial mechanical properties of the hydrogels. After swelling, the compressive strength, modulus and fracture energy of F15H1.5 NMgel decrease from ∼3.44 MPa, ∼312 kPa and ∼407.5 kJ m-3 to 0.59 MPa, ∼55 kPa, and ∼81.8 kJ m-3, respectively. The energy dissipation of the first loading-unloading cycle dramatically decreases from ∼21.5 kJ m-3 to ∼6.0 kJ m-3 as well. Nevertheless, the gel still retains excellent stiffness, toughness and self-recovery due to the dense and strong micelle linkages. In vivo studies show that the implantation of F15H1.5 hydrogel in thyroid cartilage defects of rabbit larynx effectively promotes the regeneration of cartilage after 8 weeks. These results indicate that the stiff NMgel is a promising cartilage tissue engineering scaffold for the regeneration of cartilage in vivo.

Fabrication and evaluation of non-mulberry silk fibroin fiber reinforced chitosan based porous composite scaffold for cartilage tissue engineering.

Lack of potential regenerative medicine to reconstruct damaged cartilage tissue has accelerated investigation and development of potential biomaterial for cartilage tissue engineering. In this study, we fabricated micron-sized non-mulberry silk fibroin fiber (SFF) using N,N-Dimethylacetamide (DMAC)/10% LiBr solution and further used to develop SFF reinforced chitosan(CH) based porous scaffold with desired pore size, porosity, swelling and structural stability. The developed scaffold was characterized for its various physico-chemical, mechanical and biological properties. The developed CH/SFF composite scaffold facilitates human mesenchymal stem cell (hMSCs) attachment, colonization and extracellular matrix deposition. Furthermore, hMSCs shows significantly higher sulfated glycosaminoglycan deposition over CH/SFF in comparison to pure chitosan scaffold (control). Immunocytochemistry studies have shown enhanced expression of collagen type II and aggrecan by hMSCs over composite scaffold than chitosan scaffold. Thus, non-mulberry silk fibroin fiber reinforced chitosan based scaffold might be suitable scaffold that can act as a potential artificial matrix for cartilage tissue engineering.

Characterization of Hydroxyapatite/ Silk Fibroin/ Chitosan Scaffold for Cartilage Tissue Engineering

Tissue engineering (TE) is a modern medical approach to reconstruct damage tissue in a shorter period. Scaffold is the main structure for cells adhesion and provides 3D space for cell proliferation and growth. Biomaterials were selected to fabricate a scaffold according to properties and target tissues. In this study, Hydroxyapatite (HA), Silk Fibroin (SF), and Chitosan (CS) were selected to fabricate the scaffold in different combination ratios by freeze drying (FD) technique. According to the physical properties of the fabricated scaffold, cartilage tissue was selected as a study target area for the future medical application. Scaffold characterization was performed to observe the scaffolds properties in each materials ratio. In this study, CS scaffold provided highest abilities which related to cartilage tissue structure. Moreover, the combination of SF in CS provided highest ability for cartilage cell proliferation in vitro. Therefore, CS could be used as a cartilage scaffold for cartilage TE and SF could be added to increased the cells viability of the scaffold.

Collagen Scaffolds in Cartilage Tissue Engineering and Relevant Approaches for Future Development.

Cartilage tissue engineering (CTE) aims to obtain a structure mimicking native cartilage tissue through the combination of relevant cells, three-dimensional scaffolds, and extraneous signals. Implantation of 'matured' constructs is thus expected to provide solution for treating large injury of articular cartilage. Type I collagen is widely used as scaffolds for CTE products undergoing clinical trial, owing to its ubiquitous biocompatibility and vast clinical approval. However, the long-term performance of pure type I collagen scaffolds would suffer from its limited chondrogenic capacity and inferior mechanical properties. This paper aims to provide insights necessary for advancing type I collagen scaffolds in the CTE applications. Initially, the interactions of type I/II collagen with CTE-relevant cells [i.e., articular chondrocytes (ACs) and mesenchymal stem cells (MSCs)] are discussed. Next, the physical features and chemical composition of the scaffolds crucial to support chondrogenic activities of AC and MSC are highlighted. Attempts to optimize the collagen scaffolds by blending with natural/synthetic polymers are described. Hybrid strategy in which collagen and structural polymers are combined in non-blending manner is detailed. Type I collagen is sufficient to support cellular activities of ACs and MSCs; however it shows limited chondrogenic performance than type II collagen. Nonetheless, type I collagen is the clinically feasible option since type II collagen shows arthritogenic potency. Physical features of scaffolds such as internal structure, pore size, stiffness, etc. are shown to be crucial in influencing the differentiation fate and secreting extracellular matrixes from ACs and MSCs. Collagen can be blended with native or synthetic polymer to improve the mechanical and bioactivities of final composites. However, the versatility of blending strategy is limited due to denaturation of type I collagen at harsh processing condition. Hybrid strategy is successful in maximizing bioactivity of collagen scaffolds and mechanical robustness of structural polymer. Considering the previous improvements of physical and compositional properties of collagen scaffolds and recent manufacturing developments of structural polymer, it is concluded that hybrid strategy is a promising approach to advance further collagen-based scaffolds in CTE.

Antibacterial effectiveness meets improved mechanical properties: Manuka honey/gellan gum composite hydrogels for cartilage repair

Biomaterials for cartilage repair are still far from clinical requirements, even if several studies recently focused on this topic. In this respect, Nature-derived hydrogels are a promising class of scaffolds for cartilage tissue engineering, mimicking the native cellular microenvironment. However, they frequently lack mechanical features required for cartilage applications and are commonly subjected to infection threat. This work describes the innovative use of Manuka honey as molecular spacer for preparing gellan gum-based composites with intrinsic antibacterial properties and superior compressive Young’s modulus in respect of several Nature-derived gels based on chitosan, hyaluronic acid or alginate. The addition of Manuka honey made hydrogels able to inhibit the proliferation of S. aureus and S. epidermidis clinical isolates. Furthermore, no cytotoxic effects were detected on human mesenchymal stem cells seeded on the hydrogels. Moreover, chondrogenesis experiments showed a consistent expression of collagen II and high synthesis of GAGs and proteoglycans, thus indicating the formation of cartilage matrix. Overall, these data suggest that the developed smart composites have a great potential as tools for cartilage tissue engineering.

Novel phase separated polycaprolactone/collagen scaffolds for cartilage tissue engineering

Osteoarthritis is the leading cause of pain and disability worldwide. Despite treatment availability, fully functional and suitable long term treatments for large cartilage defects are yet to be sought. Cartilage tissue engineering provides an alternative treatment option with the potential of cartilage regeneration. Previously, scaffolds have been enhanced through coating with collagen type I, however, equal distribution of collagen and collagen penetration throughout the scaffold have been poor. Herein, this study aims to employ thermally induced phase separation to fabricate porous hybrid polycaprolactone (PCL)/collagen type I scaffolds, with equally distributed collagen type I throughout the scaffold. PCL/collagen scaffolds were produced using polycaprolactone, varying concentrations of collagen type I and acetic acid as the solvent. Scaffolds were seeded with chondrocytes for 14 days. Scaffolds possessed an interconnected and porous structure, which altered with an increase in collagen concentration. Collagen type I antibody staining revealed the presence of equally distributed collagen within the PCL fibres. A reduction in collagen type I concentration influenced the compressive properties of the PCL/collagen type 1 scaffolds. Specifically, 0.2% wt/vol concentration of collagen presented to have compressive properties similar to that of the native cartilage at 10% strain. All scaffolds allowed cell attachment and collagen scaffolds showed a greater number of viable chondrocytes after 14 days of culture, compared to PCL control. This study demonstrated the ability of fabricating PCL/collagen type I scaffolds which exhibit easily tuneable porosity and compressive properties. Further investigation on the long term feasibility of these scaffolds is warranted.

Component effect of stem cell-loaded thermosensitive polypeptide hydrogels on cartilage repair

Biophysical properties of the desired biomimetic scaffolds, such as porosity and elasticity, have been proven associated with the efficacy of cartilage regeneration. In this work, the copolymers of poly(l-alanine)-block-poly(ethylene glycol)-block-poly(l-alanine) (PA-PEG-PA) and poly(l-alanine-co-l-phenylalanine)-block-poly(ethylene glycol)-block-poly(l-alanine-co-l-phenylalanine) (PAF-PEG-PAF) with different ratios of alanine to phenylalanine were synthesized. The introduction of a hydrophobic amino acid, i.e., phenylalanine, into polyalanine-based thermosensitive hydrogel led to the enhanced gelation behaviors and upregulated mechanical properties. Moreover, the increase of phenylalanine content resulted in the enlarged pore size and enhanced mechanical strength of PAF-PEG-PAF thermogel, followed by the regeneration of hyaline-like cartilage with reduced fibrous tissue formation in vivo. The findings indicated the great potential of thermosensitive polypeptide hydrogels in cartilage tissue engineering. Statement of SignificanceArticular cartilage defect has limited self-repair ability due to the lack of blood supply and innervation, which may lead to knee osteoarthritis afterwards. Injectable hydrogels are demonstrated possessing outstanding properties as biomimetic scaffolds in cartilage tissue engineering, while the effect of biophysical properties on the efficacy of cartilage regeneration has not been revealed. Herein, the poly(ethylene glycol)-polypeptide triblock copolymers with different ratios of alanine to phenylalanine were synthesized. The sol-to-gel transition temperature and the critical gelation concentration decreased as the increased amount of phenylalanine unit, resulting in the enlarged pore size and enhanced mechanical strength. These features lead to better regeneration of hyaline-like cartilage with reduced fibrous tissue formation, indicating great potential of thermosensitive polypeptide hydrogels for efficient cartilage repair.

Sulfated polysaccharide mediated TGF-β1 presentation in pre-formed injectable scaffolds for cartilage tissue engineering

In this work, a plant-derived polysaccharide carboxymethylcellulose (CMC) was chemically modified to incorporate sulfate groups to facilitate binding of cationic growth factors. The sulfated CMC (heparin mimic) was then used with CMC (glycosaminoglycan mimic) and gelatin (collagen mimic) to fabricate injectable pre-formed, macroporous scaffolds for cartilage tissue engineering. These scaffolds demonstrated high resilience and shape memory, thereby making them injectable through a 14G needle for up to 4–6 aspiration and injection cycles. Further, the scaffolds could sequester cationic proteins and growth factors (TGF-β1) through affinity-based interactions. When seeded with infrapatellar fat pad derived MSCs, the scaffolds demonstrated enhanced chondrogenesis after 28 days of in vitro culture when compared to controls. Taken together; these results demonstrate a polysaccharide-based minimally-invasive and translatable pre-formed injectable scaffold-based cell and growth factor delivery system for cartilage regeneration.

Hyaluronic Acid/Chitosan Coacervate-Based Scaffolds.

Chitosan-chloride (CHI) and sodium hyaluronate (HA), two semiflexible biopolymers, self-assemble to form nonstoichiometric coacervates. The effect of counterions was briefly investigated by preparing HA/CHI coacervates in either CaCl2 or NaCl solutions to find only a small difference in their tendency to coacervate. Higher water content in coacervates within CaCl2 was attributed to the chaotropic nature of Ca2+ ions. This effect was also evidenced with smaller pore sizes for coacervates in NaCl. Besides, for coacervation of chitosan-glutamate (CHI-G) with HA, dynamic light scattering at different charge ratios indicated a wider coacervation region for the HA/CHI-G pair than the HA/CHI. This was attributed to the chaotropic and "soft" ion nature of glutamate compared to chloride as a counterion of chitosan. Positive zeta potential values for both coacervate suspensions were explained by the contribution of charge mismatch, chain semiflexibility, and intra- and intercomplex disproportionation. Finally, HA/CHI coacervates were used to encapsulate bone marrow stem cells. While cell viabilities in HA/CHI coacervates were remarkable up to 21 days, their well-spread morphology has proved that HA/CHI coacervates are promising scaffolds for cartilage tissue engineering.

HWJECM-Derived Oriented Scaffolds with Autologous Chondrocytes for Rabbit Cartilage Defect Repairing.

Previously, we synthesized an articular cartilage extracellular matrix (ECM)-derived oriented scaffold for cartilage tissue engineering, which was biomimetic in terms of structure and biochemical composition. However, the limit resource of the cartilage-derived ECM is a hindrance for its application. In this study, we developed a new material for cartilage tissue engineering-human umbilical cord Wharton's jelly-derived ECM (hWJECM). The hWJECM has an abundant resource and similar biochemistry with cartilage ECM, and the use of it is not associated with ethical controversy. We adopted the method previously used in cartilage ECM-derived oriented scaffold preparation to generate the oriented hWJECM-derived scaffold, and the scaffold properties were tested in vitro and in vivo. The three-dimensional scaffold has a porous and well-oriented structure, with a mean pore diameter of ∼104 μm. Scanning electron microscopy and cell viability staining results demonstrated that the oriented scaffold has good biocompatibility and cell alignment. In addition, we used functional autologous chondrocytes to seed the hWJECM-derived oriented scaffold and tested the efficacy of the cell-scaffold constructs to repair the full-thickness articular cartilage defect in a rabbit model. Defects of 4 mm diameter were generated in the patellar grooves of the femurs of both knees and were implanted with chondrocyte-scaffold constructs (group A) or scaffolds alone (group B); rabbits with untreated defects were used as a control (group C). Six months after surgery, all defects in group A were filled completely with repaired tissue, and most of which were hyaline cartilage. In contrast, the defects in group B were filled partially with repaired tissue, and approximately half of these repaired tissues were hyaline cartilage. The defects in group C were only filled with fibrotic tissue. Histological grading score of group A was lower than those of groups B and C. Quantification of glycosaminoglycan indicated that newly formed cartilage in group A rabbits was comparable with normal cartilage. In conclusion, hWJECM-derived oriented scaffolds loaded with autologous chondrocytes induced cartilage repair in rabbit knees, which was comparable with native cartilage in terms of macroscopic view, microstructure, and biochemical composition.

Self-crosslinking and injectable chondroitin sulfate/pullulan hydrogel for cartilage tissue engineering

Injectable hydrogels derived from natural polysaccharides have great application prospects in cartilage tissue engineering (CTE). In this study, chondroitin sulfate was functionalized with adipic dihydrazide (CS-ADH), and pullulan was oxidized (oxPL). We fabricated a self-crosslink, biodegradable, in situ forming, injectable hydrogel by covalent hydrazone crosslinking of polysaccharides, without using extra cross-linking agents and releasing harmful byproducts under physiological conditions. The gelation time, equilibrium swelling, degradation behavior, network morphology and mechanical properties of CS-ADH/oxPL hydrogels were well manipulated by varying the weight ratio and concentration of CS-ADH and oxPL. In addition, encapsulation of rabbit articular chondrocytes in CS-ADH/oxPL hydrogels was observed after 14 days culture. Live/Dead staining assay demonstrated that the hydrogel system possessed good cytocompatibility. Sulfated glycosaminoglycan (sGAG) contents indicated that the hydrogel system favored cartilaginous extracellular matrix (ECM) deposition. Furthermore, the hydrogel system could maintain the chondrocyte phenotype and enhance chondrogenesis, which was evaluated in terms of their protein and gene expression. These features support that CS-ADH/oxPL hydrogels have a potential as an injectable cell delivery carrier scaffold in CTE.

Photopolymerized maleilated chitosan/methacrylated silk fibroin micro/nanocomposite hydrogels as potential scaffolds for cartilage tissue engineering

Hydrogels composed of natural materials exhibit great application potential in artificial scaffolds for cartilage repair as they can resemble the extracellular matrices of cartilage tissues comprised of various glycosaminoglycan and collagen. Herein, the natural polymers with vinyl groups, i.e. maleilated chitosan (MCS) and methacrylated silk fibroin (MSF) micro/nanoparticles, were firstly synthesized. The chemical structures of MCS and MSF micro/nanoparticles were investigated using Fourier transform infrared (FTIR) spectroscopy, proton nuclear magnetic resonance (1H NMR) spectroscopy, and X-ray photoelectron spectroscopy (XPS). Then MCS/MSF micro/nanocomposite hydrogels were prepared by the photocrosslinking of MCS and MSF micro/nanoparticles in aqueous solutions in the presence of the photoinitiator Darocur 2959 under UV light irradiation. A series of properties of the MCS/MSF micro/nanocomposite hydrogels including rheological property, equilibrium swelling, sol content, compressive modulus, and morphology were examined. The results showed that these behaviors could be tunable via the control of MSF content. When the MSF content was 0.1%, the hydrogel had the compressive modulus of 0.32±0.07MPa, which was in the range of that of articular cartilage. The in vitro cytotoxic evaluation and cell culture of the micro/nanocomposite hydrogels in combination with mouse articular chondrocytes were also investigated. The results demonstrated that the micro/nanocomposite hydrogels with TGF-β1 was biocompatible to mouse articular chondrocytes and could support cells attachment well, indicating their potential as tissue engineering scaffolds for cartilage repair.

Biomimetically Reinforced Polyvinyl Alcohol-Based Hybrid Scaffolds for Cartilage Tissue Engineering.

Articular cartilage has a very limited regeneration capacity. Therefore, injury or degeneration of articular cartilage results in an inferior mechanical stability, load-bearing capacity, and lubrication capability. Here, we developed a biomimetic scaffold consisting of macroporous polyvinyl alcohol (PVA) sponges as a platform material for the incorporation of cell-embedded photocrosslinkable poly(ethylene glycol) diacrylate (PEGDA), PEGDA-methacrylated chondroitin sulfate (PEGDA-MeCS; PCS), or PEGDA-methacrylated hyaluronic acid (PEGDA-MeHA; PHA) within its pores to improve in vitro chondrocyte functions and subsequent in vivo ectopic cartilage tissue formation. Our findings demonstrated that chondrocytes encapsulated in PCS or PHA and loaded into macroporous PVA hybrid scaffolds maintained their physiological phenotypes during in vitro culture, as shown by the upregulation of various chondrogenic genes. Further, the cell-secreted extracellular matrix (ECM) improved the mechanical properties of the PVA-PCS and PVA-PHA hybrid scaffolds by 83.30% and 73.76%, respectively, compared to their acellular counterparts. After subcutaneous transplantation in vivo, chondrocytes on both PVA-PCS and PVA-PHA hybrid scaffolds significantly promoted ectopic cartilage tissue formation, which was confirmed by detecting cells positively stained with Safranin-O and for type II collagen. Consequently, the mechanical properties of the hybrid scaffolds were biomimetically reinforced by 80.53% and 210.74%, respectively, compared to their acellular counterparts. By enabling the recapitulation of biomimetically relevant structural and functional properties of articular cartilage and the regulation of in vivo mechanical reinforcement mediated by cell–matrix interactions, this biomimetic material offers an opportunity to control the desired mechanical properties of cell-laden scaffolds for cartilage tissue regeneration.

A novel nano-composite scaffold for cartilage tissue engineering

In this study, a hybrid Poly (lactic-co-glycolic acid) (PLGA)/ Hyaluronic acid (Ha)/ Fibrin/ 45S Bioactive Glass (45SBG) nanocomposite scaffolds seeded with human Adipose-Derived Mesenchymal Stem Cells (hADMSCs) were investigated as a construct for osteoarthritis (OA), articular cartilage (AC), and subchondral bone defects therapies. The bioactivity and biodegradation of the nanocomposite scaffolds were assessed in simulated body fluid (SBF) and phosphate buffer saline (PBS) solution, respectively. Furthermore, MTT analysis was performed in order to determine attachment and viability of hADMSCs. Ultimately, results indicated that bioactivity were increased in nanocomposite scaffolds as compared to the pure PLGA scaffold. As well as, biodegradation assay exhibited that the addition of Ha, fibrin, and 45SBG nanoparticles could modify the degradation rate of PLGA. The nanocomposite scaffolds were not showed any cytotoxicity and the hADMSCs were attached on the scaffolds and proliferate properly. According to our investigation, it was concluded that using natural and synthetic polymers along with BG nanoparticles may provide a suitable construct and could show a beneficial role in AC tissue engineering and OA therapy.