Hydrogels For Cartilage Tissue Engineering Research Articles

Regeneration of Articular Cartilage Using Injectable Hybrid Polymer Hydrogel Incorporated With Nanoparticles

Cartilage damage is still a threat to human beings, yet there is currently no treatment available to fully restore the function of cartilage. Recently, due to their unique structures and properties, injectable hydrogels have been widely studied and have exhibited high potential for applications in therapeutic areas, especially in cartilage repair. In this review, briefly introduce the properties of cartilage, some articular cartilage injuries, and now available treatment strategies. Afterwards,the functional and fundamental requirements of injectable hydrogels in cartilage tissue engineering, as well as the main advantages of injectable hydrogels as a therapy for cartilage damage, including strong plasticity and excellent biocompatibility. Moreover, we comprehensively summarize the polymers, cells, and bioactive molecules regularly used in the fabrication of injectable hydrogel, with two kinds of gelation, i.e., physical and chemical crosslinking, which ensure the excellence design of injectable hydrogels for cartilage repair. We also include the novel hybrid injectable hydrogel incorporated with nanoparticles. Finally, we conclude with the advances of this clinical application and the challenges of injectable hydrogels used in cartilage.

Silk Fiber-Reinforced Hyaluronic Acid-Based Hydrogel for Cartilage Tissue Engineering.

A continuing challenge in cartilage tissue engineering for cartilage regeneration is the creation of a suitable synthetic microenvironment for chondrocytes and tissue regeneration. The aim of this study was to develop a highly tunable hybrid scaffold based on a silk fibroin matrix (SM) and a hyaluronic acid (HA) hydrogel. Human articular chondrocytes were embedded in a porous 3-dimensional SM, before infiltration with tyramine modified HA hydrogel. Scaffolds were cultured in chondropermissive medium with and without TGF-β1. Cell viability and cell distribution were assessed using CellTiter-Blue assay and Live/Dead staining. Chondrogenic marker expression was detected using qPCR. Biosynthesis of matrix compounds was analyzed by dimethylmethylene blue assay and immuno-histology. Differences in biomaterial stiffness and stress relaxation were characterized using a one-step unconfined compression test. Cell morphology was investigated by scanning electron microscopy. Hybrid scaffold revealed superior chondro-inductive and biomechanical properties compared to sole SM. The presence of HA and TGF-β1 increased chondrogenic marker gene expression and matrix deposition. Hybrid scaffolds offer cytocompatible and highly tunable properties as cell-carrier systems, as well as favorable biomechanical properties.

Methacrylated pullulan/polyethylene (glycol) diacrylate composite hydrogel for cartilage tissue engineering

Pullulan hydrogels are widely used in tissue engineering and drug delivery. However, these hydrogels do not meet the requirements of articular cartilage repair because of their fast degradation rate and poor mechanical strength. Herein, we fabricated a hybrid hydrogel system by combining pullulan with synthetic polymers polyethylene (glycol) diacrylate (PEGDA). In this study, pullulan was modified with methacrylic anhydride (MA) to obtain photo-crosslinkable methacrylated pullulan (PulMA). Moreover, the lithium phenyl(2,4,6-trimethylbenzoyl)phosphinate (LAP) was used as a water-soluble UV photoinitiator to form the PulMA/PEGDA hydrogel by photopolymerization strategy. Compared with the pure PulMA hydrogel, the increase of PEGDA concentration led to a slower degradation rate and an increase of residual mass from 63.9% to 86.8%. There was about 8-fold increase in storage modulus (G′) (reach to 16.0 × 103 Pa) and 13-fold increase in compressive modulus (reach to 1.17 ± 0.17 MPa) with increasing the concentration of PEGDA to 15% (w/v) in the hydrogel. In cell culture in vitro, the rabbit’s mesenchymal stem cells (MSCs) encapsulated in the PulMA/PEGDA hydrogel could adhere and proliferate, indicating that the PulMA/PEGDA hydrogel had a good biocompatibility. Furthermore, the hydrogels supported glycosaminoglycan (GAG) synthesis, and chondrogenic phenotype of MSCs with TGF-β3-containing chondrogenic medium. This study demonstrated that the photo-crosslinking PulMA/PEGDA hydrogels, with good mechanical properties and slow degradation rate are promising scaffolds for cartilage repair and regeneration.

Bioprinting of human nasoseptal chondrocytes‐laden collagen hydrogel for cartilage tissue engineering

Skin cancer patients often have tumorigenic lesions on their noses. Surgical resection of the lesions often results in nasal cartilage removal. Cartilage grafts taken from other anatomical sites are used for the surgical reconstruction of the nasal cartilage, but donor-site morbidity is a common problem. Autologous tissue-engineered nasal cartilage grafts can mitigate the problem, but commercially available scaffolds define the shape and sizes of the engineered grafts during tissue fabrication. Moreover, the engineered grafts suffer from the inhomogeneous distribution of the functional matrix of cartilage.Advances in 3D bioprinting technology offer the opportunity to engineer cartilages with customizable dimensions and anatomically shaped configurations without the inhomogeneous distribution of cartilage matrix. Here, we report the fidelity ofFreeformReversibleEmbedding ofSuspendedHydrogel(FRESH) bioprinting as a strategy to generate customizable and homogenously distributed functional cartilage matrix engineered nasal cartilage. Using FRESH andin vitrochondrogenesis, we have fabricated tissue-engineered nasal cartilage from combining bovine type I collagen hydrogel and human nasoseptal chondrocytes. The engineered nasal cartilage constructs displayed molecular, biochemical and histological characteristics akin to native human nasal cartilage.

Structural and biological investigation of chitosan/hyaluronic acid with silanized-hydroxypropyl methylcellulose as an injectable reinforced interpenetrating network hydrogel for cartilage tissue engineering

Cartilage damage continues to pose a threat to humans, but no treatment is currently available to fully restore cartilage function. In this study, a new class of composite hydrogels derived from water-soluble chitosan (CS)/hyaluronic acid (HA) and silanized-hydroxypropyl methylcellulose (Si-HPMC) (CS/HA/Si-HPMC) has been synthesized and tested as injectable hydrogels for cartilage tissue engineering when combined without the addition of a chemical crosslinking agent. Mechanical studies of CS/HA and CS/HA/Si-HPMC hydrogels showed that as Si-HPMC content increased, swelling rate and rheological properties were higher, compressive strength decreased and degradation was faster. Our results demonstrate that the CS and HA-based hydrogel scaffolds, especially the ones with 3.0% (w/v) Si-HPMC and 2.5/4.0% (w/v) CS/HA, have suitable physical performance and bioactive properties, thus provide a potential opportunity to be used for cartilage tissue engineering. In vitro studies of CS/HA and CS/HA/Si-HPMC hydrogels encapsulated in chondrocytes have shown that the proper amount of Si-HPMC increases the proliferation and deposition of the cartilage extracellular matrix. The regeneration rate of the CS/HA/Si-HPMC (3%) hydrogel reached about 79.5% at 21 days for long retention periods, indicating relatively good in vivo bone regeneration. These CS/HA/Si-HPMC hydrogels are promising candidates for tissue compatibility injectable scaffolds. The data provide proof of the principle that the resulting hydrogel has an excellent ability to repair joint cartilage using a tissue-engineered approach. RESEARCH HIGHLIGHTS An injectable hydrogel based on CS/HA/Si-HPMC composites was developed. The CS/HA/Si-HPMC hydrogel displays the tunable rheological with mechanical properties. The CS/HA/Si-HPMC hydrogel is highly porous with high swelling and degradation ratio. Increasing concentration of Si-HPMC promote an organized network in CS/HA/Si-HPMC hydrogels. Injectable CS/HA/Si-HPMC hydrogels have a high potential for cartilage tissue engineering.

Thermosensitive alginate-gelatin-nitrogen-doped carbon dots scaffolds as potential injectable hydrogels for cartilage tissue engineering applications.

Hybrid injectable and biodegradable hydrogels based on oxidized alginate/gelatin and containing nitrogen-doped carbon dots (NCDs) as a reinforcement have been fabricated and crosslinked by 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC)/N-hydroxysuccinimide (NHS) as the chemical crosslinking agents in the hydrogel system. The idea of composite hydrogels relies on the assumption that they supply a microenvironment that is convenient for the exchange of nutrients via a porous structure and cell proliferation and have mechanical characteristics that approximately match natural tissue. The effect of the NCD content on the morphology structure, mechanical strength, swelling ratio, and biodegradation has been investigated. The results indicate that nanocomposite hydrogels containing a higher content of NCDs have smaller pore sizes and higher mechanical properties. The in vitro biodegradation and swelling behavior demonstrated that increasing the amount of NCDs up to 0.06% decreased the swelling ratio and weight loss of the hydrogels. The composite hydrogels are biocompatible, as verified by the MTT assay of MG-63 cells. The N-doped graphene quantum dots considerably affect degradation and interaction within the cells and hydrogels.

Narrative review of the choices of stem cell sources and hydrogels for cartilage tissue engineering.

Stem cell-based therapy is a promising treatment for cartilage defects due to the pluripotency, abundant sources and low immunogenicity of stem cells. Hydrogels are a promising class of biomaterials for cartilage engineering and are characterized by bioactivity, degradability and elasticity as well as provide water content and mechanical support. The combination of stem cells and hydrogels opens new possibilities for cartilage tissue engineering. However, the selection of suitable types of stem cells and hydrogels is difficult. Currently, various types of stem cells, such as embryonic stem cells (ESCs), mesenchymal stem cells (MSCs), induced pluripotent stem cells (iPSCs), and peripheral blood mononuclear cells (PBMSCs), and various types of hydrogels, including natural polymers, chemically modified natural polymers and synthetic polymers, have been explored based on their potential for cartilage tissue engineering. These materials are used independently or in combination; however, there is no clear understanding of their merits and disadvantages with regard to their suitability for cartilage repair. In this article, we aim to review recent progress in the use of stem cell-hydrogel hybrid constructs for cartilage tissue engineering. We focus on the effects of stem cell types and hydrogel types on efficient chondrogenesis from cellular, preclinical and clinical perspectives. We compare and analyze the advantages and disadvantages of these cells and hydrogels with the hope of increasing discussion of their suitability for cartilage repair and present our perspective on their use for the improvement of physical and biological properties for cartilage tissue engineering.

Optimization of hyaluronic acid-tyramine/silk-fibroin composite hydrogels for cartilage tissue engineering and delivery of anti-inflammatory and anabolic drugs

Injury of articular cartilage leads to an imbalance in tissue homeostasis, and due to the poor self-healing capacity of cartilage the affected tissue often exhibits osteoarthritic changes. In recent years, injectable and highly tunable composite hydrogels for cartilage tissue engineering and drug delivery have been introduced as a desirable alternative to invasive treatments. In this study, we aimed to formulate injectable hydrogels for drug delivery and cartilage tissue engineering by combining different concentrations of hyaluronic acid-tyramine (HA-Tyr) with regenerated silk-fibroin (SF) solutions. Upon enzymatic crosslinking, the gelation and mechanical properties were characterized over time. To evaluate the effect of the hydrogel compositions and properties on extracellular matrix (ECM) deposition, bovine chondrocytes were embedded in enzymatically crosslinked HA-Tyr/SF composites (in further work abbreviated as HA/SF) or HA-Tyr hydrogels. We demonstrated that all hydrogel formulations were cytocompatible and could promote the expression of cartilage matrix proteins allowing chondrocytes to produce ECM, while the most prominent chondrogenic effects were observed in hydrogels with HA20/SF80 polymeric ratios. Unconfined mechanical testing showed that the compressive modulus for HA20/SF80 chondrocyte-laden constructs was increased almost 10-fold over 28 days of culture in chondrogenic medium which confirmed the superior production of ECM in this hydrogel compared to other hydrogels in this study. Furthermore, in hydrogels loaded with anabolic and anti-inflammatory drugs, HA20/SF80 hydrogel showed the longest and the most sustained release profile over time which is desirable for the long treatment duration typically necessary for osteoarthritic joints. In conclusion, HA20/SF80 hydrogel was successfully established as a suitable injectable biomaterial for cartilage tissue engineering and drug delivery applications.

Evolution of hydrogels for cartilage tissue engineering of the knee: A systematic review and meta-analysis of clinical studies.

In recent years, studies have boosted our knowledge about the biology and disorders of articular cartilage. In this regard, the design of hydrogel-based scaffolds has advanced to improve cartilage repair. However, the efficacy of knee cartilage repair using hydrogels remains unclear. The aim of systematic review and meta-analysis was to scrutinize the efficiency of hydrogel-based therapy in correcting cartilage defects of knee (femoral condyle, patella, tibia plateau and trochlea). The search was conducted in PubMed to gather articles published from 2004/1/1 to 2019/10/01, addressing the effects of implant of hydrogel on knee joint cartilage regeneration. The Cochrane Collaboration's tool for estimating the risk of bias was applied to check the quality of articles. The clinical data for meta-analysis was recorded using the visual analog scale (VAS), Lysholm score, WOMAC, and IKDC. The guidelines of Cochrane Handbook for Systematic Reviews of Interventions were utilized to conduct the review and meta-analysis in the RevMan 5.3 software. The search resulted in 50 clinical trials that included 2846 patients, 986 of whom received cell-based hydrogel implants while 1860 patients used hydrogel without cell. There were significant differences comparing the pain scores based on the VAS (MD: -2.97; 95% CI: -3.15 to -2.79, P<0.00001) and WOMAC (MD: -25.22; 95% CI: -31.22 to -19.22, P<0.00001) between pre- and post-treatment with hydrogels. Furthermore, there were significant improvements in the functional scores based on the IKDC total score (MD: 30.67; P<0.00001) and the Lysholm knee scale (MD: 29.26; 95% CI: 26.74 to 31.78, P<0.00001). According to the Lysholm and IKDC score and after cumulative functional analysis, there was a significant improvement in this parameter (MD: 29.25; 95% CI: 27.26 to 31.25, P<0.00001). This meta-analysis indicated clinically and statistically significant improvements in the pain score (VAS and WOMAC) and the functional score (IKDC and Lysholm) after the administration of hydrogel compared to pretreatment status. So, the current evidence shows the efficiency of hydrogel-based therapy in correcting and repairing knee cartilage defects.

Preparation and characterization of an injectable dexamethasone-cyclodextrin complexes-loaded gellan gum hydrogel for cartilage tissue engineering

In this study, 6-(6-aminohexyl) amino-6-deoxy-β-cyclodextrin-gellan gum complex hydrogel (HCD-GG) was developed to enhance the affinity of anti-inflammatory drug dexamethasone (Dx), improve chondrogenesis, and decrease the inflammatory response. The modified chemical structure was confirmed by NMR and FTIR. Mechanical and physicochemical properties were characterized by performing viscosity study, compression test, injection force test, swelling kinetic, weight loss, and morphological study. The release profile of the drug-loaded hydrogels was analyzed to confirm the affinity of the hydrophobic drugs and the matrix and characterize cumulative release. In vitro test was carried out with MTT assay, live/dead staining, glycosaminoglycan (GAGs) content, double-stranded DNA (dsDNA) content, morphological analysis, histology, and gene expression. In vivo experiment was conducted by implanting the samples under a subcutaneous area of SPD rat and cartilage defected rabbit model. The results displayed successfully synthesized HCD-GG. The gelation temperature of the modified hydrogels was decreased while the mechanical property was improved when the drug was loaded in the modified hydrogel. Swelling and degradation kinetics resulted in a higher level compared to the pristine GG but was a sufficient level to support drugs and cells. The affinity and release rate of the drug was higher in the HCD-GG group which shows an improved drug delivery system of the GG-based material. The microenvironment provided a suitable environment for cells to grow. Also, chondrogenesis was affected by the existence of Dx and microenvironment, resulting in higher expression levels of cartilage-related genes while the expression of the inflammation mediators decreased when the Dx was loaded. In vivo study showed an improved anti-inflammatory response in the drug-loaded hydrogel. Furthermore, the cartilage defected rabbit model showed an enhanced regenerative effect when the Dx@HCD-GG was implanted. These results suggest that HCD-GG and Dx@HCD-GG have the potential for cartilage regeneration along with multiple applications in tissue engineering and regenerative medicine.

Synthesis, characterization, and cytotoxicity of PCL–PEG–PCL diacrylate and agarose interpenetrating network hydrogels for cartilage tissue engineering

AbstractHydrogels are suitable biomaterials for cartilage tissue engineering due to the excellent ability to retain water to provide suitable environment for the tissue, however, the insufficient mechanical properties often prevent their wider applications. The objective of this study was to fabricate biocompatible hydrogels with good mechanical performance, high‐water content, and porous microstructure for cartilage regeneration. Photocrosslinked hydrogels are one of the most widely used systems in tissue engineering due to the superior mechanical properties. In this study, block copolymer, poly(ε ‐caprolactone)‐poly(ethylene)‐poly(ε‐caprolactone) diacrylate (PCL–PEG–PCL; PEC), was prepared by ring‐opening polymerization, and PEC hydrogels were made through free radical crosslinking mechanism. Agarose network is chosen as another component of the hydrogels, because of the high‐swelling behavior and cartilage‐like microstructure, which is helpful for chondrocytes growth. Interpenetrating networks (IPN) were fabricated by diffusing PEC into agarose network followed by photo‐crosslinking process. It was noted that incorporating PEC into the agarose network increased the elastic modulus and the compressive failure properties of individual component networks. In addition, high‐swelling ratio and uniform porosity microstructures were found in the IPN hydrogels. IPN and PEC showed low cytotoxicity and good biocompatibility in elution test method. The results suggest promising characteristics of IPN hydrogels as a potential biomaterial for cartilage tissue engineering.

Biomimetic polyvinyl alcohol/type II collagen hydrogels for cartilage tissue engineering

Type II collagen (Col-II) is one of the important organic components of the cartilage extracellular matrix (ECM). Such natural material is known for its good biocompatibility, but it could not provide a good supporting environment for seed cells due to its rapid degradation and poor strength. In the present work, different contents of Col-II were incorporated into porous polyvinyl alcohol (PVA) to fabricate porous PVA/Col-II composite hydrogels for cartilage tissue engineering. The results illustrate that, after incorporation of Col-II, the elasticity modulus of the composite hydrogels firstly increases, and then decreases (under moisture state). The elasticity modulus of PVA/Col-II (at the ratio of 1:1) hydrogels reaches 11 ± 1.7 KPa, about two-fold higher than pure PVA hydrogels (4.9 ± 0.6 KPa). Meanwhile, all hydrogels exhibit relatively high water content (> 95%) and porosity (> 75%). The degradation analysis indicates that Col-II incorporation induce a high degradation ratio of the composite hydrogels. Cell culture results show PVA/Col-II hydrogels have no negative effects on cells viability and proliferation. The PVA/Col-II hydrogels may possess a potential application in the field of articular cartilage tissue engineering and regeneration.

Development and characterization of carbohydrate-based thermosensitive hydrogels for cartilage tissue engineering

In this work, thermosensitive hydrogels formulated with methylcellulose, xanthan gum and/or carboxymethyl chitosan were developed and characterized as a potential treatment for damaged or osteoarthritic joints. The formulations produced experienced a reversible sol–gel transition upon a temperature change from room temperature to 37 °C. Three different drugs were incorporated into the hydrogels: dexamethasone, diclofenac sodium, and gallic acid. The cytotoxicity of the hydrogels was accessed and the hydrogels were also characterized regarding aspect and surface morphology, swelling, and stability, gelling temperature, compressive modulus, FT-IR and drugs release behavior. Sufficiently stable hydrogels with high culture medium absorption capacity were obtained. When freeze-dried, the hydrogels showed a highly interconnected porous structure. The compressive equilibrium and dynamic modulus were higher in the hydrogels with drugs, since gallic acid could crosslink the structures. In summary, the hydrogels produced may be effective candidates for the repair of osteoarthritic joints after minimally invasive surgery.

Advancements and Frontiers in the High Performance of Natural Hydrogels for Cartilage Tissue Engineering.

Cartilage injury originating from trauma or osteoarthritis is a common joint disease that can bring about an increasing social and economic burden in modern society. On account of its avascular, neural, and lymphatic characteristics, the poor migration ability of chondrocytes, and a low number of progenitor cells, the self-healing ability of cartilage defects has been significantly limited. Natural hydrogels, occurring abundantly with characteristics such as high water absorption, biodegradation, adjustable porosity, and biocompatibility like that of the natural extracellular matrix (ECM), have been developed into one of the most suitable scaffold biomaterials for the regeneration of cartilage in material science and tissue engineering. Notably, natural hydrogels derived from sources such as animal or human cadaver tissues possess the bionic mechanical behaviors of physiological cartilage that are required for usage as articular cartilage substitutes, by which the enhanced chondrogenic phenotype ability may be achieved by facilely embedding living cells, controlling degradation profiles, and releasing stimulatory growth factors. Hence, we summarize an overview of strategies and developments of the various kinds and functions of natural hydrogels for cartilage tissue engineering in this review. The main concepts and recent essential research found that great challenges like vascularity, clinically relevant size, and mechanical performances were still difficult to overcome because the current limitations of technologies need to be severely addressed in practical settings, particularly in unpredictable preclinical trials and during future forays into cartilage regeneration using natural hydrogel scaffolds with high mechanical properties. Therefore, the grand aim of this current review is to underpin the importance of preparation, modification, and application for the high performance of natural hydrogels for cartilage tissue engineering, which has been achieved by presenting a promising avenue in various fields and postulating real-world respective potentials.

In vitro characterization of a novel magnetic fibrin-agarose hydrogel for cartilage tissue engineering

The encapsulation of cells into biopolymer matrices enables the preparation of engineered substitute tissues. Here we report the generation of novel 3D magnetic biomaterials by encapsulation of magnetic nanoparticles and human hyaline chondrocytes within fibrin-agarose hydrogels, with potential use as articular hyaline cartilage-like tissues. By rheological measurements we observed that, (i) the incorporation of magnetic nanoparticles resulted in increased values of the storage and loss moduli for the different times of cell culture; and (ii) the incorporation of human hyaline chondrocytes into nonmagnetic and magnetic fibrin-agarose biomaterials produced a control of their swelling capacity in comparison with acellular nonmagnetic and magnetic fibrin-agarose biomaterials. Interestingly, the in vitro viability and proliferation results showed that the inclusion of magnetic nanoparticles did not affect the cytocompatibility of the biomaterials. What is more, immunohistochemistry showed that the inclusion of magnetic nanoparticles did not negatively affect the expression of type II collagen of the human hyaline chondrocytes. Summarizing, our results suggest that the generation of engineered hyaline cartilage-like tissues by using magnetic fibrin-agarose hydrogels is feasible. The resulting artificial tissues combine a stronger and stable mechanical response, with promising in vitro cytocompatibility. Further research would be required to elucidate if for longer culture times additional features typical of the extracellular matrix of cartilage could be expressed by human hyaline chondrocytes within magnetic fibrin-agarose hydrogels.

Exquisite design of injectable Hydrogels in Cartilage Repair.

Cartilage damage is still a threat to human beings, yet there is currently no treatment available to fully restore the function of cartilage. Recently, due to their unique structures and properties, injectable hydrogels have been widely studied and have exhibited high potential for applications in therapeutic areas, especially in cartilage repair. In this review, we briefly introduce the properties of cartilage, some articular cartilage injuries, and now available treatment strategies. Afterwards, we propose the functional and fundamental requirements of injectable hydrogels in cartilage tissue engineering, as well as the main advantages of injectable hydrogels as a therapy for cartilage damage, including strong plasticity and excellent biocompatibility. Moreover, we comprehensively summarize the polymers, cells, and bioactive molecules regularly used in the fabrication of injectable hydrogels, with two kinds of gelation, i.e., physical and chemical crosslinking, which ensure the excellent design of injectable hydrogels for cartilage repair. We also include novel hybrid injectable hydrogels combined with nanoparticles. Finally, we conclude with the advances of this clinical application and the challenges of injectable hydrogels used in cartilage repair.

Preparation and characterization of methacrylated gelatin/bacterial cellulose composite hydrogels for cartilage tissue engineering.

Methacrylated gelatin (GelMA)/bacterial cellulose (BC) composite hydrogels have been successfully prepared by immersing BC particles in GelMA solution followed by photo-crosslinking. The morphology of GelMA/BC hydrogel was examined by scanning electron microscopy and compared with pure GelMA. The hydrogels had very well interconnected porous network structure, and the pore size decreased from 200 to 10 µm with the increase of BC content. The composite hydrogels were also characterized by swelling experiment, X-ray diffraction, thermogravimetric analysis, rheology experiment and compressive test. The composite hydrogels showed significantly improved mechanical properties compared with pure GelMA. In addition, the biocompatility of composite hydrogels were preliminarily evaluated using human articular chondrocytes. The cells encapsulated within the composite hydrogels for 7 days proliferated and maintained the chondrocytic phenotype. Thus, the GelMA/BC composite hydrogels might be useful for cartilage tissue engineering.

Preparation of bacterial cellulose/silk fibroin double-network hydrogel with high mechanical strength and biocompatibility for artificial cartilage

Bacterial cellulose (BC) and silk fibroin (SF) double-network hydrogel with high mechanical strength and biocompatibility was synthesized by using BC as the novel polymer substrate to absorb aqueous SF solution as the modifier. Fundamental physical characterizations were carried out by scanning electron microscopy, energy dispersive spectrometry, fourier transform infrared spectrometry, X-ray diffraction and X-ray photoelectron spectroscopy. Thermogravimetric and differential thermal analysis was used to investigate the stability of the hydrogel. Strength and biocompatibility of the BC/SF hydrogel for cartilage tissue engineering were evaluated by tensile strength tester and cell culture experiments. Results reveal that the BC/SF double-network hydrogel was prepared successfully, and the hydrogel could be used as a cartilage repair material in clinical application.

Digital light processing 3D printed silk fibroin hydrogel for cartilage tissue engineering

Three-dimensional printing with Digital Lighting Processing (DLP) printer has come into the new wave in the tissue engineering for regenerative medicine. Especially for the clinical application, it needs to develop of bio-ink with biocompatibility, biodegradability and printability. Therefore, we demonstrated that Silk fibroin as a natural polymer fabricated with glycidyl-methacrylate (Silk-GMA) for DLP 3D printing. The ability of chondrogenesis with chondrocyte-laden Silk-GMA evaluated in vitro culture system and applied in vivo. DLP 3D printing system provided 3D product with even cell distribution due to rapid printing speed and photopolymerization of DLP 3D printer. Up to 4 weeks in vitro cultivation of Silk-GMA hydrogel allows to ensure of viability, proliferation and differentiation to chondrogenesis of encapsulated cells. Moreover, in vivo experiments against partially defected trachea rabbit model demonstrated that new cartilage like tissue and epithelium found surrounding transplanted Silk-GMA hydrogel. This study promises the fabricated Silk GMA hydrogel using DLP 3D printer could be applied to the fields of tissue engineering needing mechanical properties like cartilage regeneration.

Evaluation of cartilage regeneration of chondrocyte encapsulated gellan gum-based hyaluronic acid blended hydrogel

Hydrogels have shown to be advantageous in supporting damaged cartilage because of its analogous to the extracellular matrix (ECM) of cartilage tissue. However, problems such as infection and inflammation are still a challenge to be solved. In terms of tissue engineering, natural materials are more advantageous than synthetic materials in biocompatibility and biodegradability status. Herein, physically blended nature-derived gellan gum (GG) hydrogel and hyaluronic acid (HA) hydrogel is suggested as a one of solution for cartilage tissue engineering material. The purpose of this study is to determine the effect of GG/HA hydrogel in vitro and in vivo. The chemical and mechanical properties were measured to confirm the compatibility of hydrogels for cartilage tissue engineering. The viability, proliferation, morphology, and gene expression of chondrocytes encapsulated in hydrogels were examined in vitro. Furthermore, the beneficial effect of the blended hydrogel was confirmed by performing the in vivo experiment. The chemical properties of hydrogels confirmed the well physically blended hydrogels. The mechanical studies of hydrogels displayed that as the content of HA increases, the swelling ratio was higher, compressive strength decreased and degradation was faster. Therefore, to use the hydrogel of GG and HA network, the proper amount must be blended. The in vitro study of chondrocytes encapsulated GG/HA hydrogel showed that the proper amount of HA enhanced the cell growth, attachment, and gene expression. The in vivo examination verified the advantageous effect of GG/HA hydrogel. Overall results demonstrate that GG/HA hydrogel is suitable for culturing chondrocyte and can be further applied for the treatment of cartilage defects.