Native Cartilage Research Articles

Collagen Type II-Based Injectable Materials for Insitu Repair and Regeneration of Articular Cartilage Defect.

Repairing and regenerating articular cartilage defects (ACDs) have long been challenging for physicians and scientists. The rise of injectable materials provides a novel strategy for minimally invasive surgery to repair ACDs. In this study, we successfully developed injectable materials based on collagen type II, achieving hyaline cartilage repair and regeneration of ACDs. Analysis was conducted on the regenerated cartilage after materials injection. The histology staining demonstrated complete healing of the ACDs with the attainment of a hyaline cartilage phenotype. The biochemical and biomechanical properties are similar to the adjacent native cartilage without noticeable adverse effects on the subchondral bone. Further transcriptome analysis found that compared with the Native cartilage adjacent to the defect area, the Regenerated cartilage in the defect area repaired with type II collagen-based injection materials showed changes in cartilage-related pathways, as well as down-regulation of T cell receptor signaling pathways and interleukin-17 signaling pathways, which changed the immune microenvironment of the ACD area. Overall, these findings offer a promising injectable approach to treating ACDs, providing a potential solution to the challenges associated with achieving hyaline cartilage insitu repair and regeneration while minimizing damage to the surrounding cartilage.

Strong, tough, and elastic poly(vinyl alcohol)/polyacrylamide DN hydrogels based on the Hofmeister effect for articular cartilage replacement.

Traditional hydrogels are usually weak and brittle, which limit their application in articular cartilage replacement because cartilage is generally strong, tough, and elastic in nature. Therefore, it is highly desirable to construct hydrogels to mimic the mechanical properties of the native articular cartilage. Herein, in this work, poly(vinyl alcohol)/polyacrylamide (PVA/PAM) DN hydrogels were prepared by in situ polymerization, which were then treated with Hofmeister series ions (Cit3-, SO42-, and Cl-) to achieve H-PVA/PAM DN hydrogels. Among the three Hofmeister ions, the DN hydrogel treated with Cit3- (named PVA/PAM-Cit) showed the densest microstructure and the highest crystallinity degree. In this context, PVA/PAM-Cit exhibited a tensile strength of 18.9 ± 1.6 MPa, a compressive strength of 102.3 ± 7.9 MPa, a tensile modulus of 10.6 ± 2.1 MPa, a compressive modulus of 8.9 ± 0.8 MPa, and a roughness of 66.2 ± 4.2 MJ m-3, respectively, which were the highest strength and modulus, and the second highest toughness when compared with those of the reported PVA and PVA based DN hydrogels so far. It also showed an extreme high elasticity, which could maintain a stress of 99.2% after 500 cycles of fatigue testing. Additionally, PVA/PAM-Cit can promote the adhesion, spreading and proliferation of chondrocytes. These results verify that such a strong, tough, and elastic hydrogel could be a novel candidate material for articular cartilage replacement.

Standardizing Chondrocyte Isolation and Articular Cartilage Decellularization: A Versatile Bioink for Tissue Engineering Applications.

The extracellular matrix (ECM) is a noncellular component of tissues that provides structural and biochemical support to cells. The purpose of decellularization is to provide a tissue-specific niche to preserve the architecture, composition, and signaling molecules of the ECM. The current protocol discusses the standardization of chondrocyte isolation and the preparation of acellular ECM as a bioink additive from human native articular cartilage. Isolated chondrocytes with bioink additives provide a tissue-specific microenvironment. Herein, we discuss a standardized protocol with multiple applications in the area of organ-on-a-chip model development, spheroid formation, microfluidics platform, bioprinting, and tissue engineering. Cartilage tissue engineering is complex owing to the heterogeneous complex proteins, which are a challenge to synthesize; hence, this protocol in many ways offers cues to exploit the acellular ECM for multiple ongoing research studies.

Biomolecules-Loading of 3D-Printed Alginate-Based Scaffolds for Cartilage Tissue Engineering Applications: A Review on Current Status and Future Prospective.

Osteoarthritis (OA) can arise from various factor including trauma, overuse, as well as degeneration resulting from age or disease. The specific treatment options will vary based on the severity of the condition, and the affected joints. Some common treatments for OA include lifestyle modifications, medications, physical therapy, surgery and tissue engineering (TE). For cartilage tissue engineering (CTE), three-dimension (3D) scaffolds are made of biocompatible natural polymers, which allow for the regeneration of new cartilage tissue. An ideal scaffold should possess biological and mechanical properties that closely resemble those of the cartilage tissue, and lead to improved functional of knee. These scaffolds are specifically engineered to serve as replacements for damaged and provide support to the knee joint. 3D-bioprinted scaffolds are made of biocompatible materials natural polymers, which allow for the regeneration of new cartilage. The utilization of 3D bioprinting method has emerged as a novel approach for fabricating scaffolds with optimal properties for CTE applications. This method enables the creation of scaffolds that closely mimic the native cartilage in terms of mechanical characteristics and biological functionality. Alginate, that has the capability to fabricate a cartilage replacement customized for each individual patient. This polymer exhibits hydrophilicity, biocompatibility, and biodegradability, along with shear-thinning properties. These unique properties enable Alginate to be utilized as a bio-ink for 3D bioprinting method. Furthermore, chondrogenesis is the complex process through which cartilage is formed via a series of cellular and molecular signaling. Signaling pathway is as a fundamental mechanism in cartilage formation, enhanced by the incorporation of biomolecules and growth factors that induce the differentiation of stem cells. Accordingly, ongoing review is focusing to promote of 3D bioprinting scaffolds through the utilization of advanced biomolecules-loading of Alginate-based that has the capability to fabricate a cartilage replacement tailored specifically to each patient's unique needs and anatomical requirements.

Network interactions simultaneously enhance stiffness and lubricity of triple-network hydrogels.

Synthetic hydrogels displaying cartilage-mimetic bulk and surface properties may serve as cartilage substitutes. Multi-network, electrostatic hydrogels that leverage intra- and inter-network repulsive and attractive forces represent a promising approach. Herein, triple network (TN) hydrogels were prepared to obtain a combination of desired characteristics (i.e., hydration, stiffness, shear stress, and friction properties). The TN hydrogels were comprised of a negatively charged 1st network and a neutral 2nd network possessing hydrophobic associations. Presumed to significantly influence surface properties, the 3rd network charge was systematically varied as cationic, anionic, and zwitterionic. A double-network (DN) hydrogel, comprised of the same 1st and 2nd network as for the TN hydrogels, was included as a control as well as native cartilage specimens. Micro-indentation was performed with a steel ball, yielding stiffness values as well as the contact area during sliding. The lubrication in both deionized (DI) water and fetal bovine serum (FBS) was evaluated with the micro-indenter wherein the stage reciprocated in a range of speeds. All the TN hydrogels exhibited greater Youngs modulus than the DN hydrogel control. The TN bearing a cationic 3rd network exhibited an exceptionally high Youngs modulus of ≈1.4 MPa, which was even higher than that of the cartilage samples. In both DI water and FBS, for most testing speeds, the TN hydrogels exhibited lower friction coefficient (COF) values and lower shear stresses than DN hydrogel as well as the native cartilage specimens.

Anaphylatoxins and their corresponding receptors as potential drivers in cartilage calcification during osteoarthritis progression

ObjectiveThe complement cascade as major fluid phase innate immune system is activated during progression of osteoarthritis (OA). Generated anaphylatoxins and the corresponding receptors C3aR and C5aR1 are associated with the calcification of blood vessels and involved in osteogenic differentiation. This study aims on elucidating whether complement activation products contribute to cartilage calcification of OA cartilage. MethodHuman articular chondrocytes were osteogenically differentiated in vitro in the presence or absence of C3a, C5a, and bone morphogenetic protein (BMP) 2. Furthermore, macroscopically intact (OARSI grade ≤ 1) and highly degenerated human cartilage (OARSI grade ≥ 3) was used for C3aR and C5aR1 histochemistry. Calcification of the cartilage was assessed by Alizarin Red S and von Kossa staining. ResultsC3a and C5a amplified matrix mineralization during in vitro osteogenesis, while inhibition of the corresponding receptors impaired calcium deposition. Moreover, C3aR and C5aR1 expression was upregulated during osteogenic differentiation and also in degenerated cartilage. Additionally, anaphylatoxin receptor expression was positively associated with calcification of native cartilage tissue and calcium deposition during osteogenic differentiation. Finally, the pro-hypertrophic growth factor BMP2 induced the expression of C5aR1. ConclusionsOur findings indicate that anaphylatoxins and their receptors play a decisive role in cartilage calcification processes during OA progression.

Development and evaluation of 3D composite scaffolds with piezoelectricity and biofactor synergy for enhanced articular cartilage regeneration.

The inability of articular cartilage to self-repair following injuries frequently precipitates osteoarthritis, profoundly affecting patients' quality of life. Given the limitations inherent in current clinical interventions, an urgent need exists for more effective cartilage regeneration methodologies. Previous studies have underscored the potential of electrical stimulation in cartilage repair, thus motivating the investigation of innovative strategies. The present study introduces a three-dimensional scaffold fabricated through a composite technique that leverages the synergy between piezoelectricity and biofactors to enhance cartilage repair. This scaffold is composed of polylactic acid (PLLA) and barium titanate (BT) for piezoelectric stimulation and at the bottom with a collagen-coated layer infused with fibroblast growth factor-18 (FGF-18) for biofactor delivery. Designed to emulate the properties of natural cartilage, the scaffold enables controlled generation of piezoelectric charges and the sustained release of biofactors. In vitro tests confirm that the scaffold promotes chondrocyte proliferation, matrix hyperplasia, cellular migration, and the expression of genes associated with cartilage formation. Moreover, in vivo studies on rabbits have illustrated its efficacy in catalyzing the in situ regeneration of articular cartilage defects and remodeling the extracellular matrix. This innovative approach offers significant potential for enhancing cartilage repair and holds profound implications for regenerative medicine.

Functional performance of a bi-layered chitosan-nano-hydroxyapatite osteochondral scaffold: a pre-clinical in vitro tribological study.

Osteochondral grafts are used for repair of focal osteochondral lesions. Autologous grafts are the gold standard treatment; however, limited graft availability and donor site morbidity restrict use. Therefore, there is a clinical need for different graft sources/materials which replicate natural cartilage function. Chitosan has been proposed for this application. The aim of this study was to assess the biomechanics and biotribology of a bioresorbable chitosan/chitosan-nano-hydroxyapatite osteochondral construct (OCC), implanted in an in vitro porcine knee experimental simulation model. The OCC implanted in different surgical positions (flush, proud and inverted) was compared to predicate grafts in current clinical use and a positive control consisting of a stainless steel graft implanted proud of the cartilage surface. After 3 h (10 800 cycles) wear simulation under a walking gait, subsidence occurred in all OCC samples irrespective of surgical positioning, but with no apparent loss of material and low meniscus wear. Half the predicate grafts exhibited delamination and scratching of the cartilage surfaces. No graft subsidence occurred in the positive controls but wear and deformation of the meniscus were apparent. Implanting a new chitosan-based OCC either optimally (flush), inverted or proud of the cartilage surface resulted in minimal wear, damage and deformation of the meniscus.

Designing a Synthetic 3D-Printed Knee Cartilage: FEA Model, Micro-Structure and Mechanical Characteristics

Articular cartilage morphology and composition are essential factors in joint biomechanics, and their alteration is a crucial aspect of osteoarthritis (OA), a prevalent disease that causes pain and functional loss. This research focuses on developing patient-specific synthetic cartilage using innovative Digital Anatomy polymers. The objectives include investigating the morphology, characterizing the mechanical properties, and replicating the architecture of natural cartilage. This approach offers potential alternatives to traditional manufacturing methods and reduces the need for expensive in vivo experiments. Finite Element Analysis (FEA) validates a novel patient-specific measurement setup. It provides insights into the role of morphology in the distribution of stress and strain within cartilage. CAD design is also utilized to create standardized fiber-reinforced samples that mimic the layered micro-architecture of natural cartilage, allowing for the study of their contribution to the overall mechanical properties. The results demonstrate that 3D-printed polymers can effectively replicate the elastic properties of cartilage. The proposed patient-specific simulator produces reliable results, which have been validated through FEM analysis. While the recreated microstructure closely resembles biological cartilage samples, the elastic properties are slightly underestimated. In conclusion, designing an in silico knee joint is a feasible approach that offers numerous advantages for further development. The Young’s modulus values of our synthetic cartilage modules range from 2.43 MPa to 7.24 MPa, within the range reported in the literature. Moreover, Young´s modulus at the micro level shows the differences between surface 1.74 MPa and internal substrate 1.83 MPa depending on the fiber orientation. Finally, our model proves to be mechanically and morphologically accurate at both the macro and micro levels.

Sandwich hydrogel to realize cartilage-mimetic structures and performances from polyvinyl alcohol, chitosan and sodium hyaluronate

Developing artificial substitutes that mimic the structures and performances of natural cartilage is of great importance. However, it is challenging to integrate the high strength, excellent biocompatibility, low coefficient of friction, long-term wear resistance, outstanding swelling resistance, and osseointegration potential into one material. Herein, a sandwich hydrogel with cartilage-mimetic structures and performances was prepared to achieve this goal. The precursor hydrogel was obtained by freezing-thawing the mixture of poly vinyl alcohol, chitosan and deionized water three cycles, accompanied by soaking in sodium hyaluronate solution. The top of the precursor hydrogel was hydrophobically modified with lauroyl chloride and then loaded with lecithin, while the bottom was mineralized with hydroxyapatite. Due to the multiple linkages (crystalline domains, hydrogen bonds, and ionic interactions), the compressive stress was 71 MPa. Owing to the synergy of the hydrophobic modification and lecithin, the coefficient of friction was 0.01. Additionally, no wear trace was observed after 50,000 wear cycles. Remarkably, hydroxyapatite enabled the hydrogel osseointegration potential. The swelling ratio of the hydrogel was 0.06 g/g after soaking in simulated synovial fluid for 7 days. Since raw materials were non-toxic, the cell viability was 100 %. All of the above merits make it an ideal material for cartilage replacement.

Osteoarticular Open Flake Fracture Refixation: The “Parachute” Technique

Osteochondral fractures of the patella, also known as “flake fractures,” frequently occur after patellar dislocation. In such fractures, a piece of patellar cartilage with subchondral bone breaks off due to patellar dislocation or subsequent reposition. Various surgical techniques have evolved for surgical therapy with the goal of realigning the patellar cartilage. This article presents a cost-effective surgical technique for achieving stable refixation of large osteochondral fragments in patellar flake fractures. The proposed technique entails creating transosseous tunnels in a confluent fashion at the margins, exactly between the fragment and the natural cartilage. Sutures are passed through the established tunnels for flake refixation. This refixation method ensures evenly distributed pressure without penetration of the fragment itself, resulting in the formation of a characteristic parachute configuration composed of confluent bone tunnels and absorbable sutures. The suitability of flake refixation is assessed through an algorithm, allowing for appropriate patient selection. The described technique offers several advantages, including its simplicity and cost-effectiveness, a flexible configuration of the sutures, and the ability to provide stable refixation for large osteochondral fragments.

Microscale strain concentrations in tissue-engineered osteochondral implants are dictated by local compositional thresholds and architecture

Tissue-engineered osteochondral implants manufactured from condensed mesenchymal stem cell bodies have shown promise for treating focal cartilage defects. Notably, such manufacturing techniques have shown to successfully recapture the bulk mechanical properties of native cartilage. However, the relationships among the architectural features, local composition, and micromechanical environment within tissue-engineered cartilage from cell-based aggregates remain unclear. Understanding such relationships is crucial for identifying critical parameters that can predict in vivo performance. Therefore, this study investigated the relationship among architectural features, composition, and micromechanical behavior of tissue-engineered osteochondral implants. We utilized fast-confocal microscopy combined with a strain mapping technique to analyze the micromechanical behavior under quasi-static loading, as well as Fourier Transform Infrared Spectroscopy to analyze the local compositions. More specifically, we investigated the architectural features and compositional distributions generated from tissue maturation, along with macro- and micro-level strain distributions. Our results showed that under compression, cell-based aggregates underwent deformation followed by body movement, generating high local strain around the boundaries, where local aggrecan concentration was low and local collagen concentration was high. By analyzing the micromechanics and composition at the single aggregate length scale, we identified a strong threshold relationship between local strain and compositions. Namely at the aggrecan concentration below 0.015 arbitrary unit (A.U.) and the collagen concentration above 0.15 A.U., the constructs experienced greater than threefold increase in compressive strain. Overall, this study suggests that local compositional features are the primary driver of the local mechanical environment in tissue-engineered cartilage constructs, providing insight into potential quality control parameters for manufacturing tissue-engineered constructs.

Tissue adhesive, ROS scavenging and injectable PRP-based 'plasticine' for promoting cartilage repair.

Platelet-rich plasma (PRP) that has various growth factors has been used clinically in cartilage repair. However, the short residence time and release time at the injury site limit its therapeutic effect. The present study fabricated a granular hydrogel that was assembled from gelatin microspheres and tannic acid through their abundant hydrogen bonding. Gelatin microspheres with the gelatin concentration of 10 wt% and the diameter distribution of 1-10 μm were used to assemble by tannic acid to form the granular hydrogel, which exhibited elasticity under low shear strain, but flowability under higher shear strain. The viscosity decreased with the increase in shear rate. Meanwhile, the granular hydrogel exhibited self-healing feature during rheology test. Thus, granular hydrogel carrying PRP not only exhibited well-performed injectability but also performed like a 'plasticine' that possessed good plasticity. The granular hydrogel showed tissue adhesion ability and reactive oxygen species scavenging ability. Granular hydrogel carrying PRP transplanted to full-thickness articular cartilage defects could integrate well with native cartilage, resulting in newly formed cartilage articular fully filled in defects and well-integrated with the native cartilage and subchondral bone. The unique features of the present granular hydrogel, including injectability, plasticity, porous structure, tissue adhesion and reactive oxygen species scavenging provided an ideal PRP carrier toward cartilage tissue engineering.

Double-edged role of mechanical stimuli and underlying mechanisms in cartilage tissue engineering.

Mechanical stimuli regulate the chondrogenic differentiation of mesenchymal stem cells and the homeostasis of chondrocytes, thus affecting implant success in cartilage tissue engineering. The mechanical microenvironment plays fundamental roles in the maturation and maintenance of natural articular cartilage, and the progression of osteoarthritis Hence, cartilage tissue engineering attempts to mimic this environment in vivo to obtain implants that enable a superior regeneration process. However, the specific type of mechanical loading, its optimal regime, and the underlying molecular mechanisms are still under investigation. First, this review delineates the composition and structure of articular cartilage, indicating that the morphology of chondrocytes and components of the extracellular matrix differ from each other to resist forces in three top-to-bottom overlapping zones. Moreover, results from research experiments and clinical trials focusing on the effect of compression, fluid shear stress, hydrostatic pressure, and osmotic pressure are presented and critically evaluated. As a key direction, the latest advances in mechanisms involved in the transduction of external mechanical signals into biological signals are discussed. These mechanical signals are sensed by receptors in the cell membrane, such as primary cilia, integrins, and ion channels, which next activate downstream pathways. Finally, biomaterials with various modifications to mimic the mechanical properties of natural cartilage and the self-designed bioreactors for experiment in vitro are outlined. An improved understanding of biomechanically driven cartilage tissue engineering and the underlying mechanisms is expected to lead to efficient articular cartilage repair for cartilage degeneration and disease.

OPTIMIZING WOUNDED ARTICULAR CARTILAGE FOR IMPROVED CARTILAGE INTEGRATION: EVALUATING CHONDROPROTECTIVE MEASURES FOR MINIMIZING IN SITU CHONDROCYTE DEATH

AbstractObjectiveThe preparation of host degenerate cartilage for repair typically requires cutting and/or scraping to remove the damaged tissue. This can lead to mechanical injury and cartilage cell (chondrocytes) death, potentially limiting the integration of repair material. This study evaluated cell death at the site of cutting injury and determined whether raising the osmotic pressure (hyper-osmolarity) prior to injury could be chondroprotective.MethodsEx vivo human femoral head cartilage was obtained from 13 patients (5 males and 8 females: 71.8 years old) with Ethical Permission and Patient consent. Cartilage wells were created using 3 or 5mm biopsy punches. Cell death at the wounded edge of the host cartilage and the edge of the extracted explants were assessed by quantifying the percentage of cell death (PCD) and measuring the width of the cell death zone at identified regions of interest (ROI) using the confocal laser scanning microscopy and image analysis software. To assess the chondroprotective effect of hyper-osmolarity, cartilage specimens were incubated in 340 or 600mOsm media, five minutes prior to injury to allow the chondrocytes to respond to the altered osmolarity. Wounded cartilage explants and cartilage wells were then cultured for a further 150 minutes following injury.ResultsIn 340mOsm media, the PCD around the 3mm cartilage wells was significantly less compared to the corresponding explants (20.05±10.24% vs 35.25±4.86%; P=0.0003). When using the 5mm biopsy punch, the PCD at the wound edges was significantly lower when compared to the 3mm cartilage wells (13.33±7.80% vs 20.05±10.24%; P=0.0121) at the same osmolarity. The width of the cell death zone for the well edges for both 3 and 5mm punches was significantly narrower when compared to their corresponding harvested cartilage explants in 340mOsm media (P<0.0001; P=0.0218, respectively). Exposing cartilage to raised osmolarity (600mOsm) prior to injury significantly reduced the PCD for cartilage wells produced by the 3mm biopsy punches (from 20.05±10.24% to 12.24±6.00%; P=0.0025). In addition, the zone of cell death was marginally reduced at the edges of the 5mm cartilage wells (19.25±15.78mm to 12.72±9.09mm; P=0.0499).ConclusionsThe choice of biopsy punch and the osmolarity of the incubation medium prior to cartilage injury markedly affected the extent of chondrocyte death both at the edges of the cartilage wells and the explants. The smaller biopsy punch caused more chondrocyte death in the native cartilage wells compared to the larger punch, but this could be compensated for by the chondroprotective effect of raising the osmotic pressure. In general, there was less cell death at the wounded edges of the cartilage wells, compared to the explants. These results suggest that there is scope for further optimising the cutting implements used to create the cartilage wells and protecting chondrocytes by hyper-osmolarity in order to minimize cell death at cut edges and potentially enhance integration between cartilage repair material and host cartilage.Declaration of Interest(b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Construction and Properties of High-Toughness Soft-Soft Interfaces Based on the Adhesion of Natural Polyphenols.

Artificial joint replacement is the most effective way to treat osteoarthritis. However, these artificial joints are too stiff with high interfacial contact stress and poor surface lubrication, resulting in stress shielding and severe wear and tear lead to an extremely high failure rate. At present, hydrogels are considered the most promising substitute for artificial joint prostheses owing to their good biocompatibility, adjustable mechanical properties, and excellent flexibility. Nevertheless, a traditional single-layer hydrogel has poor bearing capacity and lubrication, which are far from the properties of natural articular cartilage. The high strength and low friction properties of natural articular cartilage are based on its own multilayer fibrous structure. Therefore, by simulating the multilayer structure of natural cartilage, a bilayer bionic cartilage hydrogel was prepared; that is, the upper hydrogel realized excellent lubrication and the lower hydrogel realized high load-bearing capacity. However, the interface binding of bilayer hydrogels is a challenge at present. Therefore, the interfacial adhesion of the bilayer hydrogel is improved by adding tannic acid (TA) based on the adhesion of the natural polyphenol structure. The average interfacial toughness reaches 3650 J/m2, and the average interfacial shear force reaches 800 kPa. In the preparation of the bilayer hydrogel, taking advantage of the coordination reaction between TA and metal cations, Fe3+ is further added to endow the bilayer hydrogel with excellent mechanical properties and good sliding friction performance. Therefore, this work opens up a new way to construct cartilage-like materials with high toughness and a soft-soft interface.

Using Decellularized Magnetic Microrobots to Deliver Functional Cells for Cartilage Regeneration.

The use of natural cartilage extracellular matrix (ECM) has gained widespread attention in the field of cartilage tissue engineering. However, current approaches for delivering functional scaffolds for osteoarthritis (OA) therapy rely on knee surgery, which is limited by the narrow and complex structure of the articular cavity and carries the risk of injuring surrounding tissues. This work introduces a novel cell microcarrier, magnetized cartilage ECM-derived scaffolds (M-CEDSs), which are derived from decellularized natural porcine cartilage ECM. Human bone marrow mesenchymal stem cells are selected for their therapeutic potential in OA treatments. Owing to their natural composition, M-CEDSs have a biomechanical environment similar to that of human cartilage and can efficiently load functional cells while maintaining high mobility. The cells are released spontaneously at a target location for at least 20 days. Furthermore, cell-seeded M-CEDSs show better knee joint function recovery than control groups 3 weeks after surgery in preclinical experiments, and ex vivo experiments reveal that M-CEDSs can rapidly aggregate inside tissue samples. This work demonstrates the use of decellularized microrobots for cell delivery and their in vivo therapeutic effects in preclinical tests.

Repair of full-thickness articular cartilage defects with a 3DP-anchored three-phase complex

IntroductionTo repair cartilage defect as well as the calcified cartilage layer (CCL) and bone tissue, there is need to fabricate a three-phase complex that mimics the natural cartilage tissue. Materials and methodsSF/Col-Ⅱ/HA scaffolds were constructed by low-temperature 3D printing, and to prepare a three-phase complex. The microstructure were showed using a SEM image analysis program. To observe collagen and glycosaminoglycan expression and analyze morphometric parameters, HE staining was performed to reveal new cartilage. Immunohistochemical were performed to investigate the collagen content and defect repair status in the new cartilage group in vitro and vivo. ResultsPhysical and biochemical properties and biocompatibility of three-phase complex met the requirements of constructing tissue-engineered cartilage. The OD values increased gradually at different time points. With increasing culture time, the OD values showed an upward trend. The HE and immunohistochemical staining results showed that new cartilage had formed at the defect and new cartilage formation occurred during in vivo repair. Conclusion3DP-anchored three-phase complexes have good physical and biochemical properties and biocompatibility and thus represent an alternative cartilage tissue engineering material.

Cartilage-inspired self-assembly glycopeptide hydrogels for cartilage regeneration via ROS scavenging

Cartilage injury represents a frequent dilemma in clinical practice owing to its inherently limited self-renewal capacity. Biomimetic strategy-based engineered biomaterial, capable of coordinated regulation for cellular and microenvironmental crosstalk, provides an adequate avenue to boost cartilage regeneration. The level of oxidative stress in microenvironments is verified to be vital for tissue regeneration, yet it is often overlooked in engineered biomaterials for cartilage regeneration. Herein, inspired by natural cartilage architecture, a fibril-network glycopeptide hydrogel (Nap-FFGRGD@FU), composed of marine-derived polysaccharide fucoidan (FU) and naphthalenephenylalanine-phenylalanine-glycine-arginine-glycine-aspartic peptide (Nap-FFGRGD), was presented through a simple supramolecular self-assembly approach. The Nap-FFGRGD@FU hydrogels exhibit a native cartilage-like architecture, characterized by interwoven collagen fibers and attached proteoglycans. Beyond structural simulation, fucoidan-exerted robust biological effects and Arg-Gly-Asp (RGD) sequence-provided cell attachment sites realized functional reinforcement, synergistically promoted extracellular matrix (ECM) production and reactive oxygen species (ROS) elimination, thus contributing to chondrocytes-ECM harmony. In vitro co-culture with glycopeptide hydrogels not only facilitated cartilage ECM anabolic metabolism but also scavenged ROS accumulation in chondrocytes. Mechanistically, the chondro-protective effects induced by glycopeptide hydrogels rely on the activation of endogenous antioxidant pathways associated with nuclear factor erythroid 2-related factor 2 (NRF2). In vivo implantation of glycopeptide hydrogels successfully improved the de novo cartilage generation by 1.65-fold, concomitant with coordinately restructured subchondral bone structure. Collectively, our ingeniously crafted bionic glycopeptide hydrogels simultaneously rewired chondrocytes’ function by augmenting anabolic metabolism and rebuilt ECM microenvironment via preserving redox equilibrium, holding great potential for cartilage tissue engineering.

Microgel-Modified Bilayered Hydrogels Dramatically Boosting Load-Bearing and Lubrication.

Hydrogel-based articular cartilage replacement materials are promising candidates for their potential to provide both high load-bearing capacity and low friction performance, similar to natural cartilage. Nevertheless, the design of these materials presents a significant challenge in reconciling the conflicting demands of the load-bearing capacity and lubrication. Despite extensive research in this area, there is still room for improvement in the creation of hydrogel-based materials that effectively meet these demands. Herein, a facile strategy is provided to realize simultaneously high load-bearing and low friction properties on the proposed hydrogel by modifying the surface of mechanically strong annealled PVA-PAAc hydrogel with a high hydration potential PAAm-co-PAMPS microgel. Consequently, a bilayer hydrogel with a porous surface and a compact substrate has been obtained. Compressive experiments confirmed that the bilayer hydrogel exhibited excellent mechanical strength with a compressive strength of 32.23 MPa at 90% strain. A high load-bearing (applied load up to 30 N), extremely low friction coefficiency (0.01-0.05) and excellent wear resistance (COF low to 0.03 after a 4 h test at 10 N using a steel ball as the contact pair) are successfully achieved. These findings provide new perspectives for the design of articular cartilage materials.