Scaffolds For Cartilage Tissue Engineering Research Articles

Effects of cartilage acellular solubilised ECM on physicomechanical and biological properties of polycaprolactone/fibrin hybrid scaffold fabricated by 3D-printing and salt-leaching methods

ABSTRACT Scaffold fabrication methods have a vital role in cartilage tissue engineering (CTE). For a long time, extracellular matrix (ECM) derivatives have been used to improve chondrogenesis and cartilage regeneration. In this study, polycaprolactone (PCL) scaffolds were prepared by 3D-printing and salt-leaching methods. Then, the prepared scaffolds were coated with fibrin and different acellular solubilised ECM concentrations. Adipose-derived stem cells (ADSCs) were added to fibrin/ECM hydrogel and seeded on the PCL scaffolds. Results showed that water absorption and compressive moduli of the 3D-printed scaffolds were higher than salt-leached scaffolds. As ECM was added and concentration increased, porosity was decreased and water uptake increased significantly. 3D-printed scaffolds with ECM2% group demonstrated a high compressive modulus and cell viability. Therefore, we concluded 2% is the most suitable concentration for acellular solubilised ECM in order to fabricate more biocompatible and applicable PCL/fibrin/ECM scaffolds in CTE.

Exploration of the single-walled carbon nanotubes’ influence for cartilage repair

Carboxylated single-walled carbon nanotubes has only been noted for its biocompatibility and excellent mechanical properties. Nobody has examined whether or not it facilitate repair of cartilage defects. A kind of 3-D carbon nanotubes-based composite scaffold for cartilage tissue engineering was developed. Moreover, its physicochemical and biological indexes, such as microstructure, mechanical properties, cell proliferation and cytocompatibility were examined. All these indexes manifested that the composite scaffolds with carbon nanotubes processed smaller pore opening, higher compression strength, better cell proliferation, and no cytotoxicity. Animal experiments further showed that the addition of carbon nanotubes at 0.5 wt% was most beneficial to cartilage repair than others. In conclusion, the study suggested that 0.5 wt% CNTs-based composite scaffold has a promising prospect in cartilage tissue engineering.

Combined culture experiment of mouse bone marrow mesenchymal stem cells and bioceramic scaffolds.

Articular cartilage injuries are common orthopedic conditions that severely affect the quality of life of patients. Tissue engineering can facilitate cartilage repair and the key points involve scaffolding and seed cell selection. Pre-experiments found a range of microstructures of bioceramic scaffolds suitable for chondrocyte adhesion and proliferation, and maintaining chondrocyte phenotype. Three-dimensional cultures of bone marrow mesenchymal stem cell (BMSC) scaffolds were implanted into mice. According to the shape of the bioceramic scaffolds and the implantation time in vivo, RNA sequencing was performed on the removed scaffolds to explore the molecular mechanism. The in vitro bone plate culture can induce differentiation of chondrocytes, making culture different to that produced in vitro. Implantation of scaffolds in vivo increases the expression of bone-related genes. The ceramic rod-like material was found to be superior to the disc shape, and the bone repair effect was more marked with longer implantation times. Gene Ontology analysis revealed that ‘cell chemotaxis’, ‘negative regulation of ossification’ and ‘bone development’ pathways were involved in recovery. It was further confirmed that BMSCs were suitable as seed cells for cartilage tissue engineering, and that the β-tricalcium phosphate scaffold maybe ideal as cartilage tissue engineering scaffold material. The present research provided new insights into the molecular mechanism of cartilage repair by BMSCs and bioceramic scaffolds. Bioinformatics analysis revealed that AMMECR1L-like protein, tumor necrosis factor-induced protein 2, inhibitor of nuclear factor-B kinase subunit and protein kinase C type and ‘negative regulation of ossification’ and ‘bone development’ pathways may be involved in osteoblast maturation and bone regeneration.

Crosslinker-free silk/decellularized extracellular matrix porous bioink for 3D bioprinting-based cartilage tissue engineering.

As cartilage tissue lacks the innate ability to mount an adequate regeneration response, damage to it is detrimental to the quality of life of the subject. The emergence of three-dimensional bioprinting (3DBP) technology presents an opportunity to repair articular cartilage defects. However, widespread adoption of this technique has been impeded by difficulty in preparing a suitable bioink and the toxicity inherent in the chemical crosslinking process of most bioinks. Our objective was to develop a crosslinker-free bioink with the same biological activity as the original cartilage extracellular matrix (ECM) and good mechanical strength. We prepared bioinks containing different concentrations of silk fibroin and decellularized extracellular matrix (SF-dECM bioinks) mixed with bone marrow mesenchymal stem cells (BMSCs) for 3D bioprinting. SF and dECM interconnect with each other through physical crosslinking and entanglement. A porous structure was formed by removing the polyethylene glycol from the SF-dECM bioink. The results showed the SF-dECM construct had a suitable mechanical strength and degradation rate, and the expression of chondrogenesis-specific genes was found to be higher than that of the SF control construct group. Finally, we confirmed that a SF-dECM construct that was designed to release TGF-β3 had the ability to promote chondrogenic differentiation of BMSCs and provided a good cartilage repair environment, suggesting it is an ideal scaffold for cartilage tissue engineering.

Adipose tissue-derived mesenchymal stem cells and chitosan/poly (vinyl alcohol) nanofibrous scaffolds for cartilage tissue engineering

Osteoarthritis (OA) has been defined as a chronic inflammatory joint disease characterized by progressive articular cartilage degeneration. Recently growing interest in regenerative medicine, using cell therapy and tissue engineering, where cellular components in combination with engineered scaffolds and bioactive materials were used to induce functional tissue regeneration. In the present study, nanofibrous scaffold based on chitosan (CS)/poly (vinyl alcohol) (PVA) were used to develop biologically functionalized biomaterial to mimic the extracellular matrix, allowing the human adipose tissue derived mesenchymal stem cells (ADSCs) to proliferate and differentiate to chondrogenic cells. The morphology of the nanofibrous mat was examined using field emission scanning electron microscope (FE/SEM). The characteristic functional groups and the nature of the chemical bonds between atoms were evaluated using Fourier transform infrared spectroscopy (FTIR) spectrum. Characterization of the seeded cells was morphologically evaluated by scanning electron microscopy and by flow cytometry for the expression of the stem cell surface markers. The differentiation potential was verified after chondrogenic induction by analyzing the expression of chondrogenic marker genes using real-time (RT PCR). Current study suggest significant potential for the use of ADSCs with the nanofibrous scaffolds in improving the osteoarthritis pathology.

Co-electrospun gelatin-chondroitin sulfate/polycaprolactone nanofibrous scaffolds for cartilage tissue engineering

Chondroitin sulfate and gelatin (GEL-CS) as a component of cartilage extracellular matrix were incorporated by polycaprolactone (PCL)nanofibers utilizing co-electrospinning process to fabricate composite scaffolds for inducing chondrogenesis of human bone mesenchymal stem cells (hMSCs) differentiation without using differential medium. The MTT anSSEM results illustrated supported cellular attachment and viability of hMSCs on scaffolds. Sulfated glycosaminoglycan secretion staining, genes expression of COL2a1 and SOX9 and also type Ⅱ collagen protein approved the differentiation of seeded hMSCs to chondrocytes without using any external chondrogenic differential factor. The scaffolds containing the highest GEL-CS content (2/1) exhibit better chondrogenesis differentiation results and it can be introduced as acceptable potential for cartilage tissue engineering application.

IGF-1-releasing PLGA nanoparticles modified 3D printed PCL scaffolds for cartilage tissue engineering

The aim of this study is to fabricate and test a 3D-printed PCL scaffold incorporating IGF-1-releasing PLGA nanoparticles for cartilage tissue engineering. IGF-1 loaded PLGA nanoparticles were produced by the double-emulsion method, and were incorporated onto 3D printed PCL scaffolds via PDA. Particle size, loading effciency (LE) and encapsulation effciency (EE) of the nanoparticles were examined. SEM, pore size, porosity, compression testing, contact angle, IGF-1 release kinetics of the composite scaffolds were also determined. For cell culture studies, CCK-8, Live/dead, MTT, GAG content and expression level of chondrocytes specific proteins and genes and HIF-1α were also tested. There was no difference of the nanoparticle size. And the LE and EE of IGF-1 in PLGA nanoparticles was about 5.53 ± 0.12% and 61.26 ± 2.71%, respectively. There was a slower, sustained release for all drug-loaded nanoparticles PLGA/PDA/PCL scaffolds. There was no difference of pore size, porosity, compressive strength of each scaffold. The contact angles PCL scaffolds were significant decreased when coated with PDA and PLGA nanoparticales. (p < .05) Live/dead staining showed more cells attached to the IGF-1 PLGA/PDA/PCL scaffolds. The CCK-8 and MTT assay showed higher cell proliferation and better biocompatibility of the IGF-1 PLGA/PDA/PCL scaffolds. (p < .05) GAG content, chondrogenic protein and gene expression level of SOX-9, COL-II, ACAN, and HIF pathway related gene (HIF-1α) were significantly higher in IGF-1 PLGA/PDA/PCL scaffolds group compared to other groups. (p < .05) IGF-1 PLGA/PDA/PCL scaffolds may be a better method for sustained IGF-1 administration and a promising scaffold for cartilage tissue engineering.

Effect of matrix stiffness and adhesion ligand density on chondrogenic differentiation of mesenchymal stem cells.

Adhesion ligands and mechanical properties of extracellular matrix (ECM) play significant roles in directing mesenchymal stem cells' (MSCs) behaviors, but how they affect chondrogenic differentiation of MSCs has rarely been studied. In this study, we investigated the effects of matrix stiffness and adhesion ligand density on proliferation and chondrogenic differentiation of MSCs by using UV crosslinked hydrogels comprised of methacrylated gelatin (GelMA) and poly(ethylene glycol) diacrylate (PEGDA) of different weight ratios. The PEGDA/GelMA hydrogels were fabricated by adjusting the weight ratio of PEGDA and GelMA with low or high adhesion ligand density (0.05 and 0.5% GelMA, respectively) and independent tunable stiffness (1.6, 6, and 25 kPa separately for hydrogels with 5, 10, and 15% PEGDA). MSCs presented differential behaviors to ECM by adjusting its adhesion ligand density and stiffness. Cell proliferation and chondrogenic differentiation could be enhanced with the improvement of adhesive properties and stiffness, evidenced by cell viability assay, hematoxylin-eosin staining, Safranin O staining, immunohistochemistry (Collagen types II, Col2a1), as well as the chondrogenic genes expression of Col2a1, Acan, and Sox9. This study may provide new strategies to design the scaffolds for cartilage tissue engineering.

Platelet-rich plasma combined with injectable hyaluronic acid hydrogel for porcine cartilage regeneration: a 6-month follow-up.

Based on our previous study, the utilization of an ultraviolet light photo-cross-linkable hyaluronic acid (HA) hydrogel integrated with a small molecule kartogenin-encapsulated nanoparticles obtained good reconstruction of osteochondral defects in a rabbit model, indicating the superiority of injectable hydrogel-based scaffolds in cartilage tissue engineering. Platelet-rich plasma (PRP), rich in various growth factors, proteins and cytokines, is considered to facilitate cartilage healing by stimulating cell proliferation and inducing chondrogenesis in cartilage defect site. The aim of this study was to test the therapeutic feasibility of autologous PRP combined with injectable HA hydrogel on cartilage repair. The focal cartilage defects with different critical sizes in the medial femoral condyle of a porcine model were used. At 6 months, the minipigs were sacrificed for assessment of macroscopic appearance, magnetic resonance imaging, micro-computed tomography, histology staining and biomechanics. The HA hydrogel combined with PRP-treated group showed more hyaline-like cartilage exhibited by macroscopic appearance and histological staining in terms of extracellular matrix and type II collagen without formation of hypertrophic cartilage, indicating its capacity to improve cartilage healing in the minipig model evaluated at 6 months, with full-thickness cartilage defect of 8.5 mm diameter and osteochondral defect of 6.5 mm diameter, 5 mm depth exhibiting apparent regeneration.

Characterization of polyvinyl alcohol hydrogels as tissue-engineered cartilage scaffolds using a coupled finite element-optimization algorithm

Mechanical strength along with high biocompatibility and water absorbing are among main characteristics of a desirable scaffold for cartilage tissue engineering. Having these properties, polyvinyl alcohol (PVA) can be a good option for constructing cartilage tissue engineering scaffolds. In this study, PVA hydrogel was produced by freeze-thaw crosslinking method, and its mechanical properties such as viscoelastic and hyperplastic behavior, which cannot be obtained analytically, was investigated with a coupled finite element (FE)-optimization algorithm and stress relaxation experimental data. To obtain isotropic hyper-viscoelastic constitutive parameters of PVA scaffolds, the Mooney-Rivlin and Neo-Hooke strain energy functions, in which shear and bulk moduli varies with time, were applied. Results showed that predicted mechanical responses of scaffolds by the Mooney-Rivlin model better fitted stress-relaxation experiments than those obtained by Neo-Hooke one. Also, the properties obtained from the finite element model, such as the bulk and the shear moduli, showed that, after successful in vitro and in vivo experiments, PVA hydrogel may be introduced as a cartilage substitute for future tissue engineering therapies.

Nanofibrous Wharton's jelly scaffold in combination with adipose-derived stem cells for cartilage engineering

The tissue engineering of cartilage represents a promising approach for cartilage repair, and the process includes cells, growth factors, and a scaffold. The scaffold is important for supporting, reinforcing, and organizing the regenerating tissue. Currently, Wharton's jelly (WJ) is considered an ideal scaffold material for cartilage tissue engineering because it has a similar composition, structure, and function as cartilage tissue. Here, we fabricated electrospun nanofibers composed of a decellularized WJ matrix reinforced by poly(ε-caprolactone) (PCL) and investigated the feasibility of a nanofibrous WJ/PCL scaffold with adipose-derived stem cells (ASCs) for use in cartilage regeneration. WJ was decellularized and then electrospun with PCL to form a WJ/PCL scaffold. The results indicated that the WJ/PCL scaffold possessed appropriate mechanical properties, suitable biodegradation, excellent hydrophilicity, increased adherence rate, low immunological reactivity, and good biocompatibility when compared with pure WJ or pure PCL scaffolds. Importantly, the WJ/PCL scaffold showed chondroconductive capabilities with ASC in vitro culture for 4 weeks. Our findings demonstrated that electrospun nanofibrous WJ/PCL is an appropriate scaffold for cartilage tissue engineering.

Silk fibroin/carboxymethyl chitosan hydrogel with tunable biomechanical properties has application potential as cartilage scaffold

Tissue engineering is a promising strategy for cartilage repair and regeneration. However, an ideal scaffolding material that not only mimics the biomechanical properties of the native cartilage, but also supports the chondrogenic phenotype of the seeding cells is in need. In this study, we developed a silk fibroin (SF) and carboxymethyl chitosan (CMCS) composite hydrogel with enzymatic cross-links (horseradish peroxidase and hydrogen peroxide) and β-sheet cross-links (ethanol treatment). Results of Fourier transform infrared (FTIR), thermal gravimetric analysis (TGA), and X-ray diffraction (XRD) verified that SF/CMCS composite hydrogels had a tunable β-sheet structure. Therefore, by increasing the time of ethanol treatment from 0 h to 8 h, a series of parameters including pore size (from 50 to 300 μm), equilibrium swelling (from 78.1 ± 2.6% to 91.9 ± 0.9%), degradation (from 100% to 9% reduction in mass over 56 days), rheological properties (storage modulus from 177 Pa to 88,904 Pa), and mechanical properties (compressive modulus from 13 to 829 kPa) of the hydrogels were adjusted. In particular, the material parameters of the hydrogels with 2 h ethanol treatment appeared most suitable for engineered cartilage. Furthermore, the in vitro cellular experiments showed that the hydrogels supported the adhesion, proliferation, glycosaminoglycan synthesis, and chondrogenic phenotype of rabbit articular chondrocytes. Finally, subcutaneous implantation of the hydrogels in mice showed no infections or local inflammatory responses, indicating a good biocompatibility in vivo. In conclusion, the chemical-physical cross-linking SF/CMCS composite hydrogels, with tunable material properties and degradation rate, good biocompatibility, are promising scaffolds for cartilage tissue engineering.

A combinatorial approach: Cryo-printing and electrospinning hybrid scaffolds for cartilage tissue engineering

Osteoarthritis is the predominant form of arthritis and is a leading cause of disability. Tissue engineered scaffolds are showing great promise for the treatment of cartilage defects. The cartilage consists of a complex architecture, which is greatly responsible for its properties and functions. In this study, highly porous multizone scaffolds were fabricated using both cryo-printing and electrospinning. The developed multizone scaffolds successfully mimic the complex structure of the collagen fibre orientation in the native cartilage. MSC were seeded onto the multizone scaffolds. Cell viability, DNA quantification and fluorescence staining demonstrated that these scaffolds allow MSC attachment and viability after 4 weeks of in vitro culture. Moreover, a key chondrogenesis factor, glycosaminoglycan, was maintained over 4 weeks of culture. Compressive properties of the multizone scaffolds were significantly lower in comparison to the phase separated control, making it mechanically suitable for the cartilage. Overall, this study produced multizone scaffolds which express a complex structure similar to that of the native cartilage and the results demonstrate the ability of the multizone scaffolds to act as platforms for MSC attachment and survival, highlighting the potential within cartilage tissue engineering.

Optimization of electrospray fabrication of stem cell–embedded alginate–gelatin microspheres and their assembly in 3D-printed poly(ε-caprolactone) scaffold for cartilage tissue engineering

ObjectiveOur study reports the optimization of electrospray human bone marrow stromal cell (hBMSCs)–embedded alginate–gelatin (Alg-Gel, same as following) microspheres for the purpose of their assembly in 3D-printed poly(ε-caprolactone) (PCL) scaffold for the fabrication of a mechanically stable and biological supportive tissue engineering cartilage construct. MethodsThe fabrication of the Alg-Gel microspheres using an electrospray technique was optimized in terms of polydispersity, yield of microspheres and circularity and varying fabrication conditions. PCL scaffolds were designed and printed by melt extrusion. Then, four groups were set: Alg-hBMSC microspheres cultured in the 2D well plate (Alg-hBMSCs+2D) group, Alg-Gel-hBMSC microspheres cultured in the 2D well plate (Alg-Gel-hBMSCs+2D) group, Alg-Gel-hBMSC microspheres embedded in PCL scaffold cultured in the 2D well plate (Alg-Gel-hBMSCs+2D) group and Alg-Gel-hBMSCs microspheres cultured in the 3D bioreactor (Alg-Gel-hBMSCs+3D) group. Cell viability, proliferation and chondrogenic differentiation were evaluated, and mechanical test was performed. ResultsNonaggregated, low polydispersity and almost spherical microspheres of average diameter of 200–300 μm were produced with alginate 1.5 w: v%, gelatin (Type B) concentration of 0.5 w: v % and CaCl2 coagulating bath concentration of 3.0 w: v %, using 30G needle size and 8 kV and 0.6 bar voltage and air pressure, respectively. Alginate with gelatin hydrogel improved viability and promoted hBMSC proliferation better than alginate microspheres. Interestingly, hBMSCs embedded in microspheres assembled in 3D-printed PCL scaffold and cultured in a 3D bioreactor were more proliferative in comparison to the previous two groups (p < 0.05). Similarly, the GAG content, GAG/DNA ratio as well as Coll 2 and Aggr gene expression were increased in the last two groups. ConclusionOptimization of hBMSC-embedded Alg-Gel microspheres produced by electrospray has been performed. The Alg-Gel composition selected allows conservation of hBMSC viability and supports proliferation and matrix deposition. The possibility to seed and assemble microspheres in designed 3D-printed PCL scaffolds for the fabrication of a mechanically stable and biological supportive tissue engineering cartilage construct was demonstrated. Translational potential of this articleWe optimize and demonstrate that electrospray microsphere fabrication is a cytocompatible and facile process to produce the hBMSC-embedded microsize tissue-like particles that can easily be assembled into a stable construct. This finding could have application in the development of mechanically competent stem cell–based tissue engineering of cartilage regeneration.

Aptamer-Functionalized Bioscaffold Enhances Cartilage Repair by Improving Stem Cell Recruitment in Osteochondral Defects of Rabbit Knees

Background: Recruitment of endogenous stem cells has been considered an alternative to cell injection/implantation in articular cartilage repair. Purpose: (1) To develop a cartilage tissue-engineering scaffold with clinically available biomaterials and functionalize the scaffold with an aptamer (Apt19s) that specifically recognizes pluripotent stem cells. (2) To determine whether this scaffold could recruit joint-resident mesenchymal stem cells (MSCs) when implanted into an osteochondral defect in a rabbit model and to examine the effects of cartilage regeneration. Study Design: Controlled laboratory study. Methods: The reinforced scaffold was fabricated by embedding a silk fibroin sponge into silk fibroin/hyaluronic acid–tyramine hydrogel and characterized in vitro. A cylindrical osteochondral defect (3.2 mm wide × 4 mm deep) was created in the trochlear grooves of rabbit knees. The rabbits were randomly assigned into 3 groups: Apt19s-functionalized scaffold group, scaffold-only group, and control group. Animals were sacrificed at 6 and 12 weeks after transplantation. Repaired tissues were evaluated via gross examination, histologic examination, and immunohistochemistry. Results: In vitro, this aptamer-functionalized scaffold could recruit bone marrow–derived MSCs and support cell adhesion. In vivo, the aptamer-functionalized scaffold enhanced cell homing in comparison with the aptamer-free scaffold. The aptamer-functionalized scaffold group also exhibited superior cartilage restoration when compared with the scaffold-only group and the control group. Conclusion: The Apt19s-functionalized scaffold exhibited the ability to recruit MSCs both in vitro and in vivo and achieved a better outcome of cartilage repair than the scaffold only or control in an osteochondral defect model. Clinical Relevance: The findings demonstrate a promising strategy of using aptamer-functionalized bioscaffolds for restoration of chondral/osteochondral defects via aptamer-introduced homing of MSCs.

Injectable Cholesterol-Enhanced Stereocomplex Polylactide Thermogel Loading Chondrocytes for Optimized Cartilage Regeneration.

Ideal cartilage tissue engineering requires scaffolds featuring good biocompatibility, large pore structure, high mechanical strength, as well as minimal invasion procedure. Although significant progress has been made in the development of polymer scaffolds, the construction of smart systems with all the desired properties is still emerging as a challenge. The thermogels of stereocomplex 4-arm poly(ethylene glycol)-polylactide (PEG-PLA) (scPLAgel ) and stereocomplex cholesterol-modified 4-arm PEG-PLA (scPLA-Cholgel ) from the equimolar enantiomeric 4-arm PEG-PLA and 4-arm PEG-PLA-Chol, respectively, are fabricated as scaffolds for cartilage tissue engineering. scPLA-Cholgel shows lower critical gelation temperature, higher mechanical strength, larger pore size, better chondrocyte adhesion, and slower degradation compared to scPLAgel as the benefit of cholesterol modification, which is more appropriate for cartilage regeneration. Moreover, the preservation of morphology, biomechanical property, cartilaginous specific matrix, as well as cartilaginous gene expressions of engineered cartilage mediated by scPLA-Cholgel are proven superior to those by scPLAgel . scPLA-Cholgel serves as a promising chondrocyte carrier for cartilage tissue engineering and gives an alternative solution to clinical cartilage repair.

Biomimetic poly(glycerol sebacate)/polycaprolactone blend scaffolds for cartilage tissue engineering.

Poly (glycerol sebacate) (PGS) is a synthetic polymeric material with the characteristics of controllable degradation, high plasticity and excellent biocompatibility. However, the time of PGS degradation is faster than that of cartilage regeneration, which limits its application in cartilage tissue engineering. Polycaprolactone (PCL), a widely used synthetic polymer, has appropriate biodegradability and higher mechanical strength. This study aims to make a scaffold from blends of fast degrading PGS and slowly degrading PCL, and to investigate its potential for cartilage tissue engineering applications. Scanning electron microscopic analysis indicated that the scaffolds provided favourable porous microstructures. In vitro degradation test showed that PGS/ PCL scaffolds acquired longer degradation time and better mechanical strength. PGS/PCL scaffolds seeded with Bone marrow-derived mesenchymal stem cells (BMSCs) and articular chondrocytes (ACCs) were cultured in vitro. Short-term in vitro experiments confirmed that both seeded cells could adhere and proliferate on the scaffold. Chondrogenic culture for cell-scaffold constructs confirmed BMSCs could differentiate into chondrocyte-like cells in PGS/PCL scaffolds. With tunable biodegradation, favorable mechanical properties and cytocompatibility, PGS/PCL scaffolds would potentially be suitable for the regeneration of cartilage tissue. Poly (glycerol sebacate) (PGS) is a synthetic polymeric material with the characteristics of controllable degradation, high plasticity and good biocompatibility. However, the time of PGS degradation is faster than that of cartilage regeneration, which limits its application in cartilage tissue engineering. Polycaprolactone(PCL), a widely used synthetic polymer, has appropriate biodegradability. This study aims to make a scaffold from blends of fast degrading PGS and slowly degrading PCL, and to investigate its potential for cartilage tissue engineering applications. Scanning electron microscopic analysis indicated that the scaffolds provided favourable porous microstructures. In vitro degradation test showed that PGS/ PCL scaffolds got longer degradation time with surface degradation nature. PGS/PCL scaffolds seeded with Bone marrow-derived mesenchymal stem cells (BMSCs) and articular chondrocytes (ACCs) were cultured in vitro under the same condition. Short-term in vitro experiments confirmed that both seed cells could adhere and proliferate on the scaffold. Chondrogenic culture for cell-scaffold constructs confirmed BMSCs could differentiate into chondrocyte-like cells and form cartilage-specific matrix in PGS/PCL scaffolds. With cytocompatibility and biodegradation profile, PGS/PCL scaffolds get great potential for cartilage tissue engineering.

Human umbilical cord-derived scaffolds for cartilage tissue engineering.

Since articular cartilage is an avascular tissue, it has limited self-regeneration capacity after damage. Current methods for human bone marrow-derived mesenchymal stem cell (hBM-MSC) differentiation into cartilage result in tissues with a lower quality as compared to native articular cartilage. Decellularized biological scaffolds have the potential to provide appropriate signals, in order to support cellular retention, migration, proliferation, and differentiation. Given the high amount of collagen, hyaluronic acid (HA), and glycosaminoglycan (GAG) in umbilical cord, this tissue can be considered as an abundant natural biomaterial for tissue engineering applications. Human umbilical cord-derived scaffolds were prepared, and the chondrogenic induction of hBM-MSCs loaded onto the scaffolds was investigated. Gelatin-based scaffolds as a commercial material was used as a control. The results show that hBM-MSCs in tissue-derived scaffolds have an increased expression of chondrogenic markers compared with gelatin, whereas there are no significant differences between the expression of hypertrophic and osteogenic markers between tissue and gelatin scaffolds. In conclusion, it is confirmed that umbilical cord-derived scaffolds are able to provide a native environment for the cells and can promote cartilage differentiation. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1793-1802, 2019.

Alginate Based Scaffolds for Cartilage Tissue Engineering: A Review

Many people, especially old and middle-aged, suffer from pain and disabilities caused by cartilage degradation. There are many surgical methods for cartilage treatment, however, none of them have shown acceptable results in long-term. Tissue engineering would be an acceptable approach for cartilage treatment. This includes cells, a carrier such as a matrix scaffold and signaling molecule. An ideal scaffold for cartilage tissue engineering should meet some requirements includes biocompatibility, biodegradability, and sufficient mechanical characteristic. While there are many suitable scaffolds made by natural and synthesis polymers, alginate- a natural polymer- has received good attention. Alginate offers many advantages for cartilage treatment; it has great potential in having tunable mechanical properties and easy manufacturing process. In the present paper, focusing on alginate as main scaffold constructive component, different studies on alginate based scaffolds in the form of physically, chemically and biologically crosslinked hydrogel, sponge, fiber, micro/nano particles and 3 D printed for articular cartilage tissue engineering are discussed and reviewed.

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.