Cartilage Tissue Regeneration Research Articles

Use of acellular matrices as scaffolds in cartilage regeneration - a systematic review.

Cartilage regeneration remains a significant challenge in the field of regenerative medicine. Acellular matrix-based cartilage tissue regeneration offers an innovative approach to repairing cartilage defects by providing a scaffold for new tissue growth. Its significance lies in its potential to restore joint function, mitigate pain, and improve the quality of life for patients suffering from cartilage-related injuries and conditions. Recent advances in acellular matrix-based cartilage regeneration have focused on enhancing scaffold properties for improved cell adhesion, proliferation, and differentiation. Moreover, several scaffold techniques such as combining ADM and ACM with cartilage tissue, as well as biphasic scaffolding enjoy rising research activity. Incorporating bioactive factors and advanced manufacturing techniques holds promise for producing more biomimetic scaffolds, advancing efficient cartilage repair and regeneration. Obstacles in acellular matrix-based cartilage regeneration include achieving proper integration with surrounding tissue and ensuring long-term durability of the regenerated cartilage. Further, issues such as high costs and limited availability of suitable cells for scaffold seeding must be considered. The heterogeneity and limited regenerative capabilities of cartilage need to be addressed for successful clinical translation. Research should focus on exploring advanced biomaterials and developing new techniques, regarding easily reproductible scaffolds, ideally constructed from clinically validated and readily available commercial products. Findings underline the potential of AM-based approaches, especially rising exploration of tissue-derived ADM and ACM. In future, the primary objective should not only be the regeneration of small cartilage defects, but rather focus on fully regenerating a joint or larger cartilage defect.

Development and Characterization of Heparin-Containing Hydrogel/3D-Printed Scaffold Composites for Craniofacial Reconstruction.

Regeneration of cartilage and bone tissues remains challenging in tissue engineering due to their complex structures, and the need for both mechanical support and delivery of biological repair stimuli. Therefore, the goal of this study was to develop a composite scaffold platform for anatomic chondral and osteochondral repair using heparin-based hydrogels to deliver small molecules within 3D-printed porous scaffolds that provide structure, stiffness, and controlled biologic delivery. We designed a mold-injection system to combine hydrolytically degradable hydrogels and 3D-printed scaffolds that could be employed rapidly (<30min) in operating room settings (~23°C). Micro-CT analysis demonstrated the effectiveness of our injection system through homogeneously distributed hydrogel within the pores of the scaffolds. Hydrogels and composite scaffolds exhibited efficient loading (~94%) of a small positively charged heparin-binding molecule (crystal violet) with sustained release over 14days and showed high viability of encapsulated porcine chondrocytes over 7days. Compression testing demonstrated nonlinear viscoelastic behavior where tangent stiffness decreased with scaffold porosity (porous scaffold tangent stiffness: 70%: 4.9MPa, 80%: 1.5MPa, and 90%: 0.20MPa) but relaxation was not affected. Lower-porosity scaffolds (70%) showed stiffness similar to lower ranges of trabecular bone (4-8MPa) while higher-porosity scaffolds (80% and 90%) showed stiffness similar to auricular cartilage (0.16-2MPa). Ultimately, this rapid composite scaffold fabrication method may be employed in the operating room and utilized to control biologic delivery within load-bearing scaffolds.

Unveiling the potential of chitosan-coated lipid nanoparticles in drug delivery for management of critical illness: a review.

Chitosan (CT), a natural, cationic, chemically stable molecule, biocompatible, biodegradable, nontoxic, polysaccharide derived from the deacetylation of chitin, has very uniquely surfaced as a material of promise for drug delivery and biomedical applications. For the oral, ocular, cutaneous, pulmonary, and nose-to-brain routes, CT-coated nanoparticles (CTCNPs) have numerous advantages, consisting of improved controlled drug release, physicochemical stability, improved cell and tissue interactions, and increased bioavailability and efficacy of the active ingredient. CTCNPs have a broad range of therapeutic properties including anticancer, antiviral, antifungal, anti-inflammatory, antibacterial properties, treating neurological disorders, and other diseases. This has led to substantial research into the many potential uses of CT as a drug delivery vehicle. CT has also been employed in a wide range of biomedical processes, including bone and cartilage tissue regeneration, ocular tissue regeneration, periodontal tissue regeneration, heart tissue regeneration, and wound healing. Additionally, CT has been used in cosmeceutical, bioimaging, immunization, and gene transfer applications. CT exhibits a number of biological activities, which are the basis for its remarkable potential for use as a drug delivery vehicle, and these activities are covered in detail in this article. The alterations applied to CT to obtain the necessary properties have been described.

Gelatin methacrylate/poly(2-ethyl-2-oxazoline) porous hydrogel loaded with kartogenin drug as a biocompatible scaffold for cartilage tissue regeneration

Gelatin methacrylate (GelMA) is a biocompatible, and biodegradable macromolecule developed from a natural polymer, gelatin, via covalent bonding with methacrylic groups. In this research, GelMA/poly(2-ethyl-2-oxazoline) (PEtOx) hydrogel loaded with Kartogenin (KGN) drug was developed with the aim to regenerate the extracellular matrix of cartilage. The morphology, swelling ratio, degree of hydrophilicity, biodegradability, elastic modulus, blood compatibility, drug release and cytotoxicity were assessed. The hydrogel was found to be hydrophilic, highly porous and biodegradable, with 92 % porosity and ∼ 43 % weight loss within 14 days. Mechanical testing revealed that the elastic modulus of GelMA (20 wt%)/PEtOx (45 wt%) was close to that of cartilage. Good blood compatibility and sustained drug release in the damaged cartilage tissue environment were also detected. According to flow cytometry and MTT tests, due to the presence of KGN, up to 75 % of the cells can survive and easily adhere to the developed scaffold. The results confirm the ability of GelMA/PEtOx hydrogel containing KGN to increase cell adhesion by preserving cell population combined with minimal cytotoxicity, which may be advantageous for use in cartilage regeneration following in-vivo implantation.

Facile synthesis of mechanically robust and injectable tetra-polyethylene glycol/methacrylate chitosan double-network hydrogel cartilage repair

The development of advanced hydrogel scaffolds with good biocompatibility, mechanical strength and bioactive property is highly desirable in cell growth, proliferation, and differentiation for the cartilage tissue regeneration. Herein, we reported a simple, inexpensive, feasible, and environmentally benign strategy to synthesize a biocompatible polyethylene glycol-based methacrylate-modified chitosan (PCSMA) double network (DN) hydrogel via the reversible Schiff base reaction and successive photopolymerization between the tetra-poly (ethylene glycol) aldehyde (Tetra-PEG-CHO) and methacrylate-modified chitosan (CSMA) in mild conditions. The four-terminated CHO groups were hypothesized to not only construct the whole architectural network through the dynamic pH-responsive Schiff base but also contribute to the injectable behavior and good tissue adhesion, which may furnish the surgeon with the availability of injectable and shapeless ability to fill in the gaps. Compared to the single PCS hydrogel with the main similar components of the tetra-PEG-CHO and pure CS moieties, the post-fabrication of PCSMA DN hydrogel possessed slower degradation time, denser network, and stronger mechanical stability, which could facilitate the bone marrow mesenchymal stem cell (BMSCs) activity and promote the chondrogenic differentiation for facilitating cartilage regeneration. Our study highlights the positive effects on chondrogenic performance and supports the PCSMA hydrogel as a promising tissue-engineered scaffold for the cartilage defect repair.

Application of hydrogel scaffolds as a cell substrate for cartilage tissue regeneration

Cell therapy or tissue engineering is currently one of the potentially effective strategies for repairing cartilage defects. Mesenchymal stromal cells and autologous and allogeneic chondrocytes obtained from cartilage biopsies from patients undergoing arthroscopic surgery are the most commonly used cells for tissue engineering. Matrices (scaffolds) often used during cell implantation can facilitate successful cell implantation. These can be static supporting or plastic hydrogel substances obtained by various methods from natural or synthetic materials, allowing cells to be delivered to the site damaged by injection. Significant advantages of biocompatible hydrogels in cartilage injury therapy are determined based on the properties of the natural extracellular matrix and the high plasticity required for adapting to irregular surfaces of the tissue defect and allowing injectable cell delivery. These characteristics make injectable hydrogels a promising tool for cartilage bioengineering.&#x0D; This study highlights the progress in injectable hydrogels as carriers of different cells in the repair of cartilage tissue defects, as well as the current requirements and unresolved issues related to the use of such therapeutic approaches.

Multipatterned Chondrocytes' Scaffolds by FL-MOPL with a BSA-GMA Hydrogel to Regulate Chondrocytes' Morphology.

Repairing articular cartilage damage is challenging due to its low regenerative capacity. In vitro, cartilage regeneration is a potential strategy for the functional reconstruction of cartilage defects. A hydrogel is an advanced material for mimicking the extracellular matrix (ECM) due to its hydrophilicity and biocompatibility, which is known as an ideal scaffold for cartilage regeneration. However, chondrocyte culture in vitro tends to dedifferentiate, leading to fibrosis and reduced mechanical properties of the newly formed cartilage tissue. Therefore, it is necessary to understand the mechanism of modulating the chondrocytes' morphology. In this study, we synthesize photo-cross-linkable bovine serum albumin-glycidyl methacrylate (BSA-GMA) with 65% methacrylation. The scaffolds are found to be suitable for chondrocyte growth, which are fabricated by homemade femtosecond laser maskless optical projection lithography (FL-MOPL). The large-area chondrocyte scaffolds have holes with interior angles of triangle (T), quadrilateral (Q), pentagon (P), hexagonal (H), and round (R). The FL-MOPL polymerization mechanism, swelling, degradation, and biocompatibility of the BSA-GMA hydrogel have been investigated. Furthermore, cytoskeleton and nucleus staining reveals that the R-scaffold with larger interior angle is more effective in maintaining chondrocyte morphology and preventing dedifferentiation. The scaffold's ability to maintain the chondrocytes' morphology improves as its shape matches that of the chondrocytes. These results suggest that the BSA-GMA scaffold is a suitable candidate for preventing chondrocyte differentiation and supporting cartilage tissue repair and regeneration. The proposed method for chondrocyte in vitro culture by developing biocompatible materials and flexible fabrication techniques would broaden the potential application of chondrocyte transplants as a viable treatment for cartilage-related diseases.

Advances in Polysaccharides for Cartilage Tissue Engineering Repair: A Review.

Cartilage repair has been a significant challenge in orthopedics that has not yet been fully resolved. Due to the absence of blood vessels and the almost cell-free nature of mature cartilage tissue, the limited ability to repair cartilage has resulted in significant socioeconomic pressures. Polysaccharide materials have recently been widely used for cartilage tissue repair due to their excellent cell loading, biocompatibility, and chemical modifiability. They also provide a suitable microenvironment for cartilage repair and regeneration. In this Review, we summarize the techniques used clinically for cartilage repair, focusing on polysaccharides, polysaccharides for cartilage repair, and the differences between these and other materials. In addition, we summarize the techniques of tissue engineering strategies for cartilage repair and provide an outlook on developing next-generation cartilage repair and regeneration materials from polysaccharides. This Review will provide theoretical guidance for developing polysaccharide-based cartilage repair and regeneration materials with clinical applications for cartilage tissue repair and regeneration.

Directed osteogenic differentiation of human bone marrow mesenchymal stem cells via sustained release of BMP4 from PBVHx-based nanoparticles

Bone Morphogenetic Protein 4 (BMP4) is crucial for bone and cartilage tissue regeneration, essential in medical tissue engineering, cosmetology, and aerospace. However, its cost and degradation susceptibility pose significant clinical challenges. To enhance its osteogenic activity while reducing dosage and administration frequency, we developed a novel long-acting BMP4 delivery system using poly(3-hydroxybutyrate-co-3-hydroxyvalerate-co-3-hydroxyhexanoate) (PBVHx) nanoparticles with soybean lecithin-modified BMP4 (sBP-NPs). These nanoparticles promote directed osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs) through sustained BMP4 release. sBP-NPs exhibited uniform size (100–200 nm) and surface charges, with higher BMP4 entrapment efficiency (82.63 %) compared to controls. After an initial burst release within 24 h, sBP-NPs achieved 80 % cumulative BMP4 release within 20 days, maintaining levels better than control BP-NPs with unmodified BMP4. Co-incubation and nanoparticle uptake experiments confirmed excellent biocompatibility of sBP-NPs, promoting hBMSC differentiation towards osteogenic lineage with increased expression of type I collagen, calcium deposition, and ALP activity (> 20,000 U/g protein) compared to controls. Moreover, hBMSCs treated with sBP-NPs exhibited heightened expression of osteogenic genetic markers, surpassing control groups. Hence, this innovative strategy of sustained BMP4 release from sBP-NPs holds potential to revolutionize bone regeneration in minimally invasive surgery, medical cosmetology or space environments.

Tunable structure and linear viscoelastic properties of poly(glycerol adipate urethane)-based elastomeric composites for tissue regeneration

Elastomeric biocomposites based on poly(glycerol adipate urethane) and hydroxyapatite were fabricated for tissue regeneration. The poly(glycerol adipate urethane) (PGAU) elastomeric composite matrices were obtained by chemical crosslinking of the poly(glycerol adipate) prepolymer (pPGA) with diisocyanate derivative of L-lysine. Two series of composites varying in the amount of L-lysine diisocyanate ethyl ester (LDI) used as a crosslinking agent were manufactured. As a ceramic filler both unmodified and L-lysine surface-modified hydroxyapatite (HAP) particles were used. The novelty of our research consists in the manufactured elastomeric materials and characterization of their linear viscoelastic (LVE) properties. The LVE properties of the composites were investigated by means of dynamic thermomechanical analysis. Frequency sweep and amplitude sweep measurements were performed in shear mode. The influence of the crosslinking agent (LDI) amount, HAP content and surface modification of HAP on the LVE properties of the composites was determined based on the analysis of the master curves of storage (G′) and loss (G″) moduli and of tanδ of the composites. Depending on the amount of LDI, HAP and surface modification, the materials differ in the values of rubber elasticity plateau modulus (G0) and G′ and G″ determined at selected shear frequencies and at the glassy state. G0 ranges from 278 kPa to 3.98 MPa, G′ in the glassy state is within the range of 219 MPa–459 MPa. The G0 values of the PGAU-based composites are within the stiffness range of soft tissue. In view of the choice of HAP as the ceramic component and the G0 values, elastomeric composites have the potential to be used as filling materials in small bone defects (due to their mechanical similarity to osteoid) as well as materials for cartilage tissue regeneration.

Isolation and Culturing of Primary Murine Chondroprogenitor Cells: A Mammalian Model of Chondrogenesis.

Embryonic limb bud-derived micromass cultures are valuable tools for investigating cartilage development, tissue engineering, and therapeutic strategies for cartilage-related disorders. This collection of fine-tuned protocols used in our laboratories outlines step-by-step procedures for the isolation, expansion, and differentiation of primary mouse limb bud cells into chondrogenic micromass cultures. Key aspects covered in these protocols include synchronized fertilization of mice (Basic Protocol 1), tissue dissection, cell isolation, micromass formation, and culture optimization parameters, such as cell density and medium composition (Basic Protocol 2). We describe techniques for characterizing the chondrogenic differentiation process by histological analysis (Basic Protocol 3). The protocols also address common challenges encountered during the process and provide troubleshooting strategies. This fine-tuned comprehensive protocol serves as a valuable resource for scientists working in the fields of developmental biology, cartilage tissue engineering, and regenerative medicine, offering an updated methodology for the study of efficient chondrogenic differentiation and cartilage tissue regeneration. © 2024 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Synchronized fertilization of mice Basic Protocol 2: Micromass culture of murine embryonic limb bud-derived cells Basic Protocol 3: Qualitative assessment of cartilage matrix production using Alcian blue staining.

Effects of Leukocyte-rich platelet-rich plasma and Leukocyte-poor platelet-rich plasma on cartilage in a rabbit osteoarthritis model.

Osteoarthritis is a prevalent chronic disease. One of its primary pathological processes involves the degeneration of articular cartilage. Platelet-rich plasma (PRP) contains cytokines and growth factors that can stimulate the repair and regeneration of articular cartilage tissues. PRP may also slow the progression of osteoarthritis. The purpose of this experiment is to compare the efficacy of Leukocyte poor (LP) - PRP and Leukocyte rich (LR) - PRP in treating rabbit osteoarthritis and to investigate their mechanisms of action. Analyzing the impact of leukocytes on PRP therapeutic effectiveness will provide a valuable clinical reference for the choice of which PRP is better for the treatment of osteoarthritis. A rabbit osteoarthritis model was established by injecting papain into the knee joint cavity, and LP-PRP and LR-PRP were prepared through different centrifugation methods for injection into the knee joint cavity. Eight weeks after injection, rabbit knee cartilage specimens were observed for gross changes, HE staining, senna O-solid green staining, and immunohistochemistry of type II collagen and were quantitatively compared using Pelletier's score, Mankin's pathology score, and ImageJ image processing software. Injection of papain into the knee joint cavity successfully established a rabbit model of osteoarthritis. All three evaluation indexes differed significantly from those of the blank group (P<0.05). LP-PRP and LR-PRP exhibited therapeutic effects when compared with the model group. The two PRP groups had similar gross tissue appearance and pathology (P>0.05). The LR-PRP group had higher collagen type-II expression (P < 0.05) than the LP-PRP group. Both LP-PRP and LR-PRP proved therapeutic for the rabbit papain osteoarthritis model. The difference in leukocyte content between the two groups did not yield different cartilage morphology or other factors by 8 weeks posttreatment. LR-PRP displayed the ability to release more factors relevant to the metabolism of type II collagen than LP-PRP, enabling the preservation of into cartilage collagen content of type II collagen and delaying osteoarthritis progression.

Regulation of Oxygen Tension as a Strategy to Control Chondrocytic Phenotype for Cartilage Tissue Engineering and Regeneration.

Cartilage defects and osteoarthritis are health problems which are major burdens on health care systems globally, especially in aging populations. Cartilage is a vulnerable tissue, which generally faces a progressive degenerative process when injured. This makes it the 11th most common cause of global disability. Conservative methods are used to treat the initial phases of the illness, while orthopedic management is the method used for more progressed phases. These include, for instance, arthroscopic shaving, microfracturing and mosaicplasty, and joint replacement as the final treatment. Cell-based implantation methods have also been developed. Despite reports of successful treatments, they often suffer from the non-optimal nature of chondrocyte phenotype in the repair tissue. Thus, improved strategies to control the phenotype of the regenerating cells are needed. Avascular tissue cartilage relies on diffusion for nutrients acquisition and the removal of metabolic waste products. A low oxygen content is also present in cartilage, and the chondrocytes are, in fact, well adapted to it. Therefore, this raises an idea that the regulation of oxygen tension could be a strategy to control the chondrocyte phenotype expression, important in cartilage tissue for regenerative purposes. This narrative review discusses the aspects related to oxygen tension in the metabolism and regulation of articular and growth plate chondrocytes and progenitor cell phenotypes, and the role of some microenvironmental factors as regulators of chondrocytes.

An Anti-Oxidative Bioink for Cartilage Tissue Engineering Applications.

Since chondrocytes are highly vulnerable to oxidative stress, an anti-oxidative bioink combined with 3D bioprinting may facilitate its applications in cartilage tissue engineering. We developed an anti-oxidative bioink with methacrylate-modified rutin (RTMA) as an additional bioactive component and glycidyl methacrylate silk fibroin as a biomaterial component. Bioink containing 0% RTMA was used as the control sample. Compared with hydrogel samples produced with the control bioink, solidified anti-oxidative bioinks displayed a similar porous microstructure, which is suitable for cell adhesion and migration, and the transportation of nutrients and wastes. Among photo-cured samples prepared with anti-oxidative bioinks and the control bioink, the sample containing 1 mg/mL of RTMA (RTMA-1) showed good degradation, promising mechanical properties, and the best cytocompatibility, and it was selected for further investigation. Based on the results of 3D bioprinting tests, the RTMA-1 bioink exhibited good printability and high shape fidelity. The results demonstrated that RTMA-1 reduced intracellular oxidative stress in encapsulated chondrocytes under H2O2 stimulation, which results from upregulation of COLII and AGG and downregulation of MMP13 and MMP1. By using in vitro and in vivo tests, our data suggest that the RTMA-1 bioink significantly enhanced the regeneration and maturation of cartilage tissue compared to the control bioink, indicating that this anti-oxidative bioink can be used for 3D bioprinting and cartilage tissue engineering applications in the future.

Adipose derived stem cells versus micro-fragmented adipose tissue in cartilage tissue regeneration and repair

Adipose derived stem cells versus micro-fragmented adipose tissue in cartilage tissue regeneration and repair

Advanced Therapeutic Medicinal Products in Bone and Cartilage Defects.

The number of patients with functional loss of bone and cartilage tissue has shown an increasing trend. Insufficient or inappropriate conventional treatments applied for trauma, orthopedic diseases, or other bone and cartilage-related disorders can lead to bone and cartilage damage. This represents a worldwide public health issue and a significant economic burden. Advanced therapeutic medicinal products (ATMPs) proposed promising alternative therapeutic modalities by application of cell-based and tissue engineering approaches. Recently, several ATMPs have been developed to promote bone and cartilage tissue regeneration. Fifteen ATMPs, two related to bone and 13 related to cartilage, have received regulatory approval and marketing authorization. However, four ATMPs were withdrawn from the market for various reasons. However, ATMPs that are still on the market have demonstrated positive results, their broad application faced limitations. The development and standardization of methodologies will be a major challenge in the coming decades. Currently, the number of ATMPs in clinical trials using mesenchymal stromal cells or chondrocytes indicates a growing recognition that current ATMPs can be improved. Research on bone and cartilage tissue regeneration continues to expand. Cell-based therapies are likely to be clinically supported by the new ATMPs, innovative fabrication processes, and enhanced surgical approaches. In this study, we highlighted the available ATMPs that have been used in bone and cartilage defects and discussed their advantages and disadvantages in clinical applications.

Novel multifunctional bioactive glass incorporated alginate/poly(amidoamine) hydrogels with controlled drug release for cartilage tissue regeneration

Novel multifunctional bioactive glass incorporated alginate/poly(amidoamine) hydrogels with controlled drug release for cartilage tissue regeneration

3D printed hybrid scaffolds do not induce adverse inflammation in mice and direct human BM-MSC chondrogenesis in vitro

Biomaterials that can improve the healing of articular cartilage lesions are needed. To address this unmet need, we developed novel 3D printed silica/poly(tetrahydrofuran)/poly(ε-caprolactone) (SiO2/PTHF/PCL-diCOOH) hybrid scaffolds. Our aim was to carry out essential studies to advance this medical device towards functional validation in pre-clinical trials. First, we show that the chemical composition, microarchitecture and mechanical properties of these scaffolds were not affected by sterilisation with gamma irradiation. To evaluate the systemic and local immunogenic reactivity of the sterilised 3D printed hybrid scaffolds, they were implanted subcutaneously into Balb/c mice. The scaffolds did not trigger a systemic inflammatory response over one week of implantation. The interaction between the host immune system and the implanted scaffold elicited a local physiological reaction with infiltration of mononuclear cells without any signs of a chronic inflammatory response.Then, we investigated how these 3D printed hybrid scaffolds direct chondrogenesis in vitro. Human bone marrow-derived mesenchymal stem/stromal cells (hBM-MSCs) seeded within the 3D printed hybrid scaffolds were cultured under normoxic or hypoxic conditions, with or without chondrogenic supplements. Chondrogenic differentiation assessed by both gene expression and protein production analyses showed that 3D printed hybrid scaffolds support hBM-MSC chondrogenesis. Articular cartilage-specific extracellular matrix deposition within these scaffolds was enhanced under hypoxic conditions (1.7 or 3.7 fold increase in the median of aggrecan production in basal or chondrogenic differentiation media).Our findings show that 3D printed SiO2/PTHF/PCL-diCOOH hybrid scaffolds have the potential to support the regeneration of cartilage tissue.

Electroactive Biomaterials Regulate the Electrophysiological Microenvironment to Promote Bone and Cartilage Tissue Regeneration

AbstractThe incidence of large bone and articular cartilage defects caused by traumatic injury is increasing worldwide; the tissue regeneration process for these injuries is lengthy due to limited self‐healing ability. Endogenous bioelectrical phenomenon has been well recognized to play an important role in bone and cartilage homeostasis and regeneration. Studies have reported that electrical stimulation (ES) can effectively regulate various biological processes and holds promise as an external intervention to enhance the synthesis of the extracellular matrix, thereby accelerating the process of bone and cartilage regeneration. Hence, electroactive biomaterials have been considered a biomimetic approach to ensure functional recovery by integrating various physiological signals, including electrical, biochemical, and mechanical signals. This review will discuss the role of endogenous bioelectricity in bone and cartilage tissue, as well as the effects of ES on cellular behaviors. Then, recent advances in electroactive materials and their applications in bone and cartilage tissue regeneration are systematically overviewed, with a focus on their advantages and disadvantages as tissue repair materials and performances in the modulation of cell fate. Finally, the significance of mimicking the electrophysiological microenvironment of target tissue is emphasized and future development challenges of electroactive biomaterials for bone and cartilage repair strategies are proposed.

Ferrous/Ferric Ions Crosslinked Type II Collagen Multifunctional Hydrogel for Advanced Osteoarthritis Treatment.

Osteoarthritis (OA) is a highly prevalent and intricate degenerative joint disease affecting an estimated 500 million individuals worldwide. Collagen-based hydrogels have sparked immense interest in cartilage tissue engineering, but substantial challenges persist in developing biocompatible and robust crosslinking strategies, as well as improving their effectiveness against the multifaceted nature of OA. Herein, a novel discovery wherein the simple incorporation of ferrous/ferric ions enables efficient dynamic crosslinking of type II collagen, leading to the development of injectable, self-healing hydrogels with 3D interconnected porous nanostructures, is unveiled. The ferrous/ferric ions crosslinked type II collagen hydrogels demonstrate exceptional physical properties, such as significantly enhanced mechanical strength, minimal swelling ratios, and remarkable resistance to degradation, while also exhibiting extraordinary biocompatibility and bioactivity, effectively promoting cell proliferation, adhesion, and chondrogenic differentiation. Additionally, the hydrogels reveal potent anti-inflammatory effects by upregulating anti-inflammatory cytokines while downregulating pro-inflammatory cytokines. In a rat model of cartilage defects, these hydrogels exhibit impressive efficacy, substantially accelerating cartilage tissue regeneration through enhanced collagen deposition and increased proteoglycan secretion. The innovative discovery of the multifunctional role of ferrous/ferric ions in endowing type II collagen hydrogels with a myriad of beneficial properties presents exciting prospects for developing advanced biomaterials with potential applications in OA.