Native Cartilage Research Articles

Effect of Mild Conditions on PVA-Based Theta Gel Preparation: Thermal and Rheological Characterization

Polyvinyl alcohol (PVA), possessing a strong ability to form hydrogels, has been widely used for various pharmaceutical and biomedical applications. In particular, the use of PVA-PEG in the form of theta gels for altered cartilage treatment has attracted an enormous amount of attention in the last 20 years. In this paper, we prepared 42 PVA-PEG in the form of theta gels at room temperature in an aqueous environment, testing the crystallization occurrence at basic pH (10 or 12). Using a statistical approach, the effect of PEG molecular weight, PVA molecular weight and alkaline pH values on water content and mechanical performance was evaluated. The used procedure permitted the theta gels to maintain swelling properties comparable to those of human cartilage, from 60% to 85%, with both polymers having the same influence. PEG MW mainly affected the hydrophilic properties, whereas the thermal properties were mostly influenced by the PVA. The shear and compression mechanical behavior of the produced materials were affected by both the polymers’ MWs. The sample obtained using PVA 125 kDa with PEG 20 kDa as a porogen appeared to be the most suitable one for cartilage disease treatment, as it had an equilibrium shear modulus in the range of 50–250 kPa, close to that of native articular cartilage, as well as optimal mechanical response under compression along the entire analyzed frequency range with a mean value of 0.12 MPa and a coefficient of friction (COF) which remained under 0.10 for all the tested sliding speeds (mm/s).

Refixation of osteochondral flake fractures after patellar dislocation-The parachute technique

Patellar dislocations are acommon occurrence in orthopedic practice, often accompanied by osteochondral fractures of the retropatellar cartilage surface, known as flake fractures, in up to 58% of cases. The parachute technique represents asimple and cost-effective surgical option aimed at restoring osteochondral integration and preserving native cartilage. Flake fracture of the patella with osteochondral fragments. Patella fracture. By utilizing transpatellar, absorbable sutures, astable osteochondral interface is achieved without penetrating the fragment itself. Postoperative treatment involves partial weight-bearing with amaximum of 20 kg for 6weeks in full knee extension. In addition, the range of motion of knee flexion is limited to30° and is increased by30° every 2weeks. To examine the short- to medium-term clinical outcomes, all patients with acute patellar dislocation treated using the parachute technique between 01/2012 and 11/2022 were included. Clinical outcomes were assessed using the visual analog scale (VAS), Tegner Activity Scale (TAS), Kujala Score, Knee Injury and Osteoarthritis Outcome Score (KOOS), and International Knee Documentation Committee (IKDC). Out of 20patients, 19 (10men, 11right-sided, 95% follow-up rate) could be recruited for postoperative evaluation. The average follow-up period was 62.5 ± 20.5 months. The clinical outcome scores yielded the following results: VAS 0.5 ± 1.6, TAS 5.8 ± 2.2, Kujala 89.4 ± 12.5, KOOS 87.8 ± 14.1, and IKDC 86.7 ± 14.3. Overall, 18patients (90.0%) expressed willingness to undergo the procedure again. At the time of follow-up, 19patients (95.0%) were satisfied with the surgical outcome. One patient (23-year-old man) required revision. None of the included patients suffered from the recurrence of patellar dislocation. In summary, the parachute technique demonstrated excellent clinical function in the short- to medium-term follow-up for acute patellar dislocation.

Effects of Losartan and Fisetin on Microfracture-Mediated Cartilage Repair of Ankle Cartilage in a Rabbit Model.

Microfracture is one surgical treatment strategy for osteochondral lesions of the talus (OLTs) but results in fibrocartilage repair tissue, which has inferior mechanical properties to native hyaline cartilage. Biological regulation of microfracture has been suggested to improve the quality of cartilage repair in patients. To determine if administration of losartan, fisetin, or losartan and fisetin combined can enhance microfracture-mediated cartilage repair of OLTs in a rabbit model. Controlled laboratory study. Four-month-old female rabbits were divided into the following groups (8 rabbits per group): microfracture only (microfracture), microfracture plus losartan (losartan), microfracture plus fisetin (fisetin), and microfracture plus losartan and fisetin (losartan+fisetin). A 2.7-mm osteochondral defect and 4 microfracture holes were created in the talar dome cartilage. The rabbits were administered losartan (10 mg/kg/day), fisetin (20 mg/kg/day), or losartan and fisetin orally until euthanized 12 weeks after surgery. Gross evaluation, micro-computed tomography, histology, and immunohistochemistry evaluations of the osteochondral defects were performed as well as quantitative polymerase chain reaction of capsule tissue and enzyme-linked immunosorbent assay of serum. The losartan and fisetin groups had increased International Cartilage Regeneration & Joint Preservation Society macroscopic scores with improved cartilage repair and enhanced subchondral bone healing compared with the microfracture group. However, the losartan+fisetin group did not show a synergistic effect. O'Driscoll histology scores were higher in the losartan and fisetin groups compared with the microfracture group, while the losartan+fisetin group had a lower score than the losartan, fisetin, and microfracture groups. Collagen type 2 staining revealed organized chondrocytes in the losartan and fisetin groups, but the losartan+fisetin group did not show improvement when compared with other groups. Fisetin treatment decreased catalase and transforming growth factor-β1-activated kinase 1 expression in capsular tissue. Concomitant microfracture and biological regulation, using oral administration of either losartan or fisetin, may improve cartilage healing of OLTs; however, losartan and fisetin combined in the current drug administration regimen does not appear to provide synergistic effects. Oral intake of losartan or fisetin may result in beneficial effects on microfracture-mediated cartilage repair of OLTs.

Hemiarthroplasty in young patients.

The survival of humeral hemiarthroplasties in patients with relatively intact glenoid cartilage could theoretically be extended by minimizing the associated postoperative glenoid erosion. Ceramic has gained attention as an alternative to metal as a material for hemiarthroplasties because of its superior tribological properties. The aim of this study was to assess the in vitro wear performance of ceramic and metal humeral hemiarthroplasties on natural glenoids. Intact right cadaveric shoulders from donors aged between 50 and 65 years were assigned to a ceramic group (n = 8, four male cadavers) and a metal group (n = 9, four male cadavers). A dedicated shoulder wear simulator was used to simulate daily activity by replicating the relevant joint motion and loading profiles. During testing, the joint was kept lubricated with diluted calf serum at room temperature. Each test of wear was performed for 500,000 cycles at 1.2 Hz. At intervals of 125,000 cycles, micro-CT scans of each glenoid were taken to characterize and quantify glenoid wear by calculating the change in the thickness of its articular cartilage. At the completion of the wear test, the total thickness of the cartilage had significantly decreased in both the ceramic and metal groups, by 27% (p = 0.019) and 29% (p = 0.008), respectively. However, the differences between the two were not significant (p = 0.606) and the patterns of wear in the specimens were unpredictable. No significant correlation was found between cartilage wear and various factors, including age, sex, the size of the humeral head, joint mismatch, the thickness of the native cartilage, and the surface roughness (all p > 0.05). Although ceramic has better tribological properties than metal, we did not find evidence that its use in hemiarthroplasty of the shoulder in patients with healthy cartilage is a better alternative than conventional metal humeral heads.

Outcomes Following Autologous Osteochondral Transplantation for Osteochondral Lesions of the Talus at 10-Year Follow-Up: A Retrospective Review.

The purpose of this study was to evaluate outcomes following autologous osteochondral transplantation (AOT) for the treatment of osteochondral lesions of the talus (OLT) at a minimum of 10-year follow-up. Retrospective chart review identified patients who underwent AOT for the treatment of OLT. Pre-operative magnetic resonance imaging (MRI) scans were obtained in all patients. Clinical outcomes assessed included: pre- and post-operative foot and ankle outcome score (FAOS), visual analog scale (VAS), patient satisfaction, complications, failures and secondary surgical procedures. Thirty-nine patients with a mean lesion size was 122.3 ± 64.1 mm2 and mean follow-up time of 138.9 ± 16.9 months were included. The mean FAOS scores improved from a preoperative score of 51.9 ± 16.0 to 75.3 ± 21.9 (P < 0.001). Increasing lesion size was variable associated with inferior FAOS scores (R2 = 0.2228). There was statistically significant higher mean T2 relaxation values at the superficial layer at the site of the AOT graft (42.9 ± 5.2 ms) compared to the superficial layer of the adjacent native cartilage (35.8 ± 3.8 ms) (P < 0.001). Seventeen complications (43.6%) were observed, the most common of which was anterior ankle impingement (25.6%). There were 2 failures (5.1%), both of which had a history of prior bone marrow stimulation via microfracture and post-operative cysts identified on MRI. This retrospective review found that AOT for the treatment of large OLTs produced a 94.9% survival rate at a minimum of 10-year follow-up. Increasing lesion size was associated with inferior clinical outcomes. The findings of this study indicates that AOT is a viable long-term surgical strategy for the treatment of large OLTs.

Fabrication of Zinc(II) Mediated Poly(Acrylamide Co Acrylic Acid) Hydrogel with Thixotropic and Tribological Properties.

Hydrogels have emerged as promising candidates for biomedical applications, such as replacing natural articular cartilage, owing to their unique viscoelastic properties. However, sufficient mechanical properties, self-healing ability, and adhesive nature are some issues limiting its application window. Here, a facile one-pot synthesis of dual cross-linked zinc-coordinated copolymer hydrogels is presented. The network structure of the copolymer hydrogels is strategically developed via dynamic and reversible physical cross-linking by Zn2+ ions and simultaneous covalent cross-linking through a covalent cross-linker viz methylene bisacrylamide. Fourier-transform infrared (FTIR), X-ray diffraction (XRD) scanning electron microscopy (SEM), and Brunauer-Emmett-Teller (BET) analysis have thoroughly characterized the structure of the synthesized hydrogels. The introduction of Zn2+ offers dynamic and reversible complexation, leading to excellent mechanical properties and self-healing features. Moreover, the percentage of the equilibrium water content of zinc-coordinated copolymer hydrogel samples is comparable with that of natural articular cartilage. The Shear sliding study shows the dominant adhesive behavior of HGel-Zn(NO3)2 sample compared to the parent HGel sample. This facile dual cross-linked hydrogel, HGel-Zn(NO3)2, with a combination of good mechanical properties, efficient self-recovery, adequate water content, and favorable adhesive nature, seems very promising to mimic the articular cartilage.

ALB–PRF facilitates chondrogenesis by promoting chondrocytes migration, proliferation and differentiation

Cartilage injury is common in orthopedics and cartilage tissue engineering provides a therapeutic direction for cartilage regeneration. Albumin (ALB)–platelet-rich fibrin (PRF) is speculated to be an ideal natural scaffold material for cartilage tissue engineering theoretically as a product derived from human venous blood. Through in vitro and in vivo experiments, it was demonstrated that ALB–PRF displayed porous structure and slowly released growth factors (TGF-β1, PDGF-AA, PDGF-AB, PDGF-BB, EGF, IGF-1 and VEGF), ALB–PRF conditioned media promoted proliferation, migration, adhesion, phenotype maintenance and extracellular matrix secretion of rabbit chondrocytes. Moreover, ALB–PRF facilitated chondrogenesis in vivo, the regenerative cartilage formed by ALB–PRF/chondrocytes was histologically similar to that of natural knee joint cartilage, the regenerative cartilage expressed cartilage differentiation marker (SOX9, ACAN and COL II), and proliferation marker PCNA and secreted abundant glycosaminoglycans (GAGs) in extracellular matrix. In conclusion, ALB–PRF promoted the migration, proliferation and phenotype maintenance of chondrocytes in vitro. Its loose, porous structure and rich growth factors contained enhanced cell adhesion and growing into the materials. ALB–PRF facilitated chondrogenesis of chondrocytes in vivo.

Autoinduction-Based Quantification of In Situ TGF-β Activity in Native and Engineered Cartilage.

Transforming growth factor beta (TGF-β) is a potent growth factor that regulates the homeostasis of native cartilage and is administered as an anabolic supplement for engineered cartilage growth. The quantification of TGF-β activity in live tissues in situ remains a significant challenge, as conventional activity assessments (e.g., Western blotting of intracellular signaling molecules or reporter cell assays) are unable to measure absolute levels of TGF-β activity in three-dimensional tissues. In this study, we develop a quantification platform established on TGF-β's autoinduction response, whereby active TGF-β (aTGF-β) signaling in cells induces their biosynthesis and secretion of new TGF-β in its latent form (LTGF-β). As such, cell-secreted LTGF-β can serve as a robust, non-destructive, label-free biomarker for quantifying in situ activity of TGF-β in live cartilage tissues. Here, we detect LTGF-β1 secretion levels for bovine native tissue explants and engineered tissue constructs treated with varying doses of media-supplemented aTGF-β3 using an isoform-specific ELISA. We demonstrate that: 1) LTGF-β secretion levels increase proportionally to aTGF-β exposure, reaching 7.4- and 6.6-fold increases in native and engineered cartilage, respectively; 2) synthesized LTGF-β exhibits low retention in both native and engineered cartilage tissue; and 3) secreted LTGF-β is stable in conditioned media for 2 weeks, thus enabling a reliable biological standard curve between LTGF-β secretion and exposed TGF-β activity. Accordingly, we perform quantifications of TGF-β activity in bovine native cartilage, demonstrating up to 0.59 ng/mL in response to physiological dynamic loading. We further quantify the in situ TGF-β activity in aTGF-β-conjugated scaffolds for engineered tissue, which exhibits 1.81 ng/mL of TGF-β activity as a result of a nominal 3 μg/mL loading dose. Overall, cell-secreted LTGF-β can serve as a robust biomarker to quantify in situ activity of TGF-β in live cartilage tissue and can be potentially applied for a wide range of applications, including multiple tissue types and tissue engineering platforms with different cell populations and scaffolds.

Meniscal scaffolds based on self-healable elastomer-hydrogel composites with biomimetic structure and tribological properties for repairing meniscal injuries

Meniscal injuries are increasing dramatically with the aging of the population and the prevalence of sports. Tissue engineering technology is the most promising method for the treatment of meniscal injuries, but the preparation of long-term and durable meniscal scaffolds with mechanical and tribological properties like natural articular cartilage remains a great challenge. Here, inspired by the structure and lubrication mechanism of the meniscus, a durable meniscus scaffold with bionic 3D structure, self-lubrication, and intelligent drug release function is prepared. An elastomer-hydrogel composite consisting of a direct ink writing (DIW) printed elastomer skeleton and a hydrogel matrix is prepared for the meniscus scaffold. The bionic 3D structure of the scaffolds is realized by combining computer-aided structural design and 3D printing technology. The self-healing ability obtained by incorporating dynamic covalent bonds, and the robust interface achieved by co-curing of the elastomer and hydrogel resins, ensure the stability and durability of the composite meniscal scaffolds. Taking advantage of the coexistence of aqueous and oily phases in the emulsion-type hydrogel resin, a hydrophobic phospholipid is loaded into the hydrogel, and achieves excellent boundary lubrication of the composite through its fiction-response release and self-assembly. Moreover, the meniscus scaffolds enable intelligent drug release to adapt to the physiological characteristics during inflammation. In vivo tests in rabbit models validate the protective effect of the scaffold on cartilage. These methods and concepts provide a solid foundation for the preparation of bionic tissue scaffolds.

Cell Mediated Reactions Create TGF-β Delivery Limitations in Engineered Cartilage

During native cartilage development, endogenous TGF-β activity is tightly regulated by cell-mediated chemical reactions in the extracellular milieu (e.g., matrix and receptor binding), providing spatiotemporal control in a manner that is localized and short acting. These regulatory paradigms appear to be at odds with TGF-β delivery needs in tissue engineering (TE) where administered TGF-β is required to transport long distances or reside in tissues for extended durations. In this study, we perform a novel examination of the influence of cell-mediated reactions on the spatiotemporal distribution of administered TGF-β in cartilage TE applications. Reaction rates of TGF-β binding to cell-deposited ECM and TGF-β internalization by cell receptors are experimentally characterized in bovine chondrocyte-seeded tissue constructs. TGF-β binding to the construct ECM exhibits non-linear Brunauer–Emmett–Teller (BET) adsorption behavior, indicating that as many as seven TGF-β molecules can aggregate at a binding site. Cell-mediated TGF-β internalization rates exhibit a biphasic trend, following a Michaelis-Menten relation (Vmax=2.4 molecules cell-1 s-1, Km=1.7 ng mL-1) at low ligand doses (≤130ng/mL), but exhibit an unanticipated non-saturating power trend at higher doses (≥130ng/mL). Computational models are developed to illustrate the influence of these reactions on TGF-β spatiotemporal delivery profiles for conventional TGF-β administration platforms. For TGF-β delivery via supplementation in culture medium, these reactions give rise to pronounced steady state TGF-β spatial gradients; TGF-β concentration decays by ∼90% at a depth of only 500 μm from the media-exposed surface. For TGF-β delivery via heparin-conjugated affinity scaffolds, cell mediated internalization reactions significantly reduce the TGF-β scaffold retention time (160 to 360-fold reduction) relative to acellular heparin scaffolds. This work establishes the significant limitations that cell-mediated chemical reactions engender for TGF-β delivery and highlights the need for novel delivery platforms that account for these reactions to achieve optimal TGF-β exposure profiles. Statement of SignificanceDuring native cartilage development, endogenous TGF-β activity is tightly regulated by cell-mediated chemical reactions in the extracellular milieu (e.g., matrix and receptor binding), providing spatiotemporal control in a manner that is localized and short acting. However, the effect of these reactions on the delivery of exogenous TGF-β to engineered cartilage tissues remains not well understood. In this study, we demonstrate that cell-mediated reactions significantly restrict the delivery of TGF-β to cells in engineered cartilage tissue constructs. For delivery via media supplementation, reactions significantly limit TGF-β penetration into constructs. For delivery via scaffold loading, reactions significantly limit TGF-β residence time in constructs. Overall, these results illustrate the impact of cell-mediated chemical reaction on TGF-β delivery profiles and support the importance of accounting for these reactions when designing TGF-β delivery platforms for promoting cartilage regeneration.

Innovating Lubrication with Polyelectrolyte Hydrogels: Sustained Performance Through Lipid Dynamics

AbstractThe lubrication process of natural joint cartilage involves a series of coordinated mechanisms, a key aspect of which is its ability to continuously extract lubricating components from synovial fluid to achieve sustained lubrication. Inspired by this natural phenomenon, this study reports a novel polyelectrolyte hydrogel, specifically integrating ε‐poly‐L‐lysine (ε‐PL), adeptly captures lipids from environment to achieve effective lubrication similar to human joints. The ε‐PL within the hydrogel facilitates the dynamic sequestration of lipids, fostering interfacial self‐assembly. This setup, enriched with highly hydrated lipid head groups, enhances boundary lubrication capabilities for extended performance. Through rigorous evaluation of friction coefficients and supramolecular interactions between the hydrogel and lipids, it identified hydrogen bonding, charge‐dipole, and hydrophobic interactions as key to this self‐assembly. The findings affirm the versatility of polyelectrolytes in synthesizing lubricating hydrogels, bridging the gap to the creation of biomimetic hydrogels that mimic natural lubrication with enhanced durability and efficiency.

An Evidence-Based Update on Fixation Procedures for Acute and Chronic Osteochondral Lesions of the Talus.

Osteochondral lesions of the talus (OLT) involve the subchondral bone and the overlying articular cartilage. Various surgical treatments for these lesions are available, such as bone marrow stimulation (BMS), autologous osteochondral grafting, and fixation of an osteochondral fragment. Treatment choice depends on the condition of the lesion, which includes lesion size, morphology, location, and the presence of cysts. Among the surgical procedures available to date, in situ fixation of the osteochondral fragment has the advantage of restoring the articular surface while preserving the native hyaline cartilage and its subchondral bone. Fixation for OLT has been shown to be clinically successful for the treatment of both acute and chronic lesions. Moreover, the indication for osteochondral fragment fixation is expanding as recent studies have found good clinical outcomes in relatively small-sized lesions. The present article describes the current evidence on fixation for acute and chronic OLT.

Biomimetic Layered Hydrogel Coating for Enhanced Lubrication and Load-Bearing Capacity

Biomimetic hydrogel lubrication coatings with high wettability and low friction show great promise in tissue engineering, wound dressing, drug delivery, and intelligent sensing. Inspired by the hierarchical structure of natural cartilage, a layered hydrogel coating was constructed to functionalize rigid polyetheretherketone (PEEK). The layered hydrogel coating features a structural design comprising a top soft layer and a middle robust layer. The porous structure of the top soft hydrogel layer stores water molecules, providing surface lubrication, while the dense structure of the middle robust hydrogel layer offers load-bearing capacity. These synergistic effects of the gradient hydrogel layer endow the PEEK substrate with an ultra-low coefficient of friction (COF~0.010 at 5 N load), good load-bearing capacity (COF~0.031 at 10 N load), and excellent wear resistance (COF &lt; 0.05 at 5 N load after 20,000 sliding cycles). This study introduces a novel design paradigm for robust hydrogel coatings with exceptional lubricity, displaying the potential application in cartilage replacement materials.

Collagen-based 3D printed poly (glycerol sebacate) composite scaffold with biomimicking mechanical properties for enhanced cartilage defect repair

Cartilage defect repair with optimal efficiency remains a significant challenge due to the limited self-repair capability of native tissues. The development of bioactive scaffolds with biomimicking mechanical properties and degradation rates matched with cartilage regeneration while simultaneously driving chondrogenesis, plays a crucial role in enhancing cartilage defect repair. To this end, a novel composite scaffold with hierarchical porosity was manufactured by incorporating a pro-chondrogenic collagen type I/II-hyaluronic acid (CI/II-HyA) matrix to a 3D-printed poly(glycerol sebacate) (PGS) framework. Based on the mechanical enforcement of PGS framework, the composite scaffold exhibited a compressive modulus of 167.0 kPa, similar to that of native cartilage, as well as excellent fatigue resistance, similar to that of native joint tissue. In vitro degradation tests demonstrated that the composite scaffold maintained structural, mass, and mechanical stability during the initial cartilage regeneration period of 4 weeks, while degraded linearly over time. In vitro biological tests with rat-derived mesenchymal stem cell (MSC) revealed that, the composite scaffold displayed increased cell loading efficiency and improved overall cell viability due to the incorporation of CI/II-HyA matrix. Additionally, it also sustained an effective and high-quality MSC chondrogenesis and abundant de-novo cartilage-like matrix deposition up to day 28. Overall, the biomimetic composite scaffold with sufficient mechanical support, matched degradation rate with cartilage regeneration, and effective chondrogenesis stimulation shows great potential to be an ideal candidate for enhancing cartilage defect repair.

Label-free 3D molecular imaging of living tissues using Raman spectral projection tomography

The ability to image tissues in three dimensions (3D) with label-free molecular contrast at the mesoscale would be a valuable capability in biology and biomedicine. Here, we introduce Raman spectral projection tomography (RSPT) for volumetric molecular imaging with optical sub-millimeter spatial resolution. We have developed a RSPT imaging instrument capable of providing 3D molecular contrast in transparent and semi-transparent samples. We also created a computational pipeline for multivariate reconstruction to extract label-free spatial molecular information from Raman projection data. Using these tools, we demonstrate imaging and visualization of phantoms of various complex shapes with label-free molecular contrast. Finally, we apply RSPT as a tool for imaging of molecular gradients and extracellular matrix heterogeneities in fixed and living tissue-engineered constructs and explanted native cartilage tissues. We show that there exists a favorable balance wherein employing Raman spectroscopy, with its advantages in live cell imaging and label-free molecular contrast, outweighs the reduction in imaging resolution and blurring caused by diffuse photon propagation. Thus, RSPT imaging opens new possibilities for label-free molecular monitoring of tissues.

Injectable decellularized extracellular matrix hydrogel with cell-adaptable supramolecular network enhances cartilage regeneration by regulating inflammation and facilitating chondrogenesis

Osteoarthritis, characterized by progressive loss of cartilage, affects millions of people worldwide and clinically lacks effective treatments. Herein, we present an injectable, biodegradable supramolecular decellularized extracellular matrix (dECM) hydrogel, which can be injected into the joints and provide biomimetic microenvironments to drive cartilage regeneration. Benefiting from the cell-adaptable dynamic network and cartilage-specific compositions, the supramolecular dECM hydrogel not only enhances cell proliferation and migration, but also facilitates chondrogenesis. Furthermore, compared with the conventional dECM hydrogels, the supramolecular dECM hydrogel is instrumental in regulating inflammation, which consequently leads to a marked suppression of genes linked to cell death and cartilage degradation. In vivo analysis confirms that stem cells, when delivered via the supramolecular dECM hydrogel, remain viable for up to three months within the restored cartilage. The regenerated tissue exhibits hyaline-cartilage structure, good mechanical properties, and cartilage-specific extracellular matrix deposition that align closely with those of native cartilage. We envision that this supramolecular dECM hydrogel could serve as a valuable platform for cartilage regeneration and could strongly facilitate the clinical translation of dECM-based materials for tissue regeneration.

Rapid preparation of injectable dual-network hydrogels for biomedical applications using UV-triggered sulfhydryl click reactions

The use of hydrogels to mimic natural cartilage implantation can effectively solve the current problems of insufficient cartilage donors and low rate of injury healing. In particular, injectable hydrogels are less invasive in clinical applications and better able to fill uneven injury surfaces. Here, we prepared NorCS and CS-SH by modifying chitosan with 5-norbornene-2-carboxylic acid and N-Acetyl-L-cysteine, respectively. Dual-network hydrogels were prepared by using UV-triggered thiol-ene click reaction between NorCS and CS-SH and the metal coordination between SA and Ca2+. The prepared hydrogels can be cross-linked quickly and exhibit excellent degradability, self-healing and injectable properties. At the same time, the hydrogel also showed good cytocompatibility and could significantly restore the motor function of mice. This study provides an effective strategy for preparing injectable hydrogels capable of rapid cross-linking.

An in situ forming cartilage matrix mimetic hydrogel scavenges ROS and ameliorates osteoarthritis after superficial cartilage injury

Superficial cartilage defects represent the most prevalent type of cartilage injury encountered in clinical settings, posing significant treatment challenges. Here, we fabricated a cartilage extracellular matrix mimic hydrogel (GHC, consisting of Gelatin, Hyaluronic acid, and Chondroitin sulfate) to avoid the exacerbation of cartilage deterioration, which is often driven by the accumulation of reactive oxygen species (ROS) and a pro-inflammatory microenvironment. The GHC hydrogel exhibited multifunctional properties, including in situ formation, tissue adhesiveness, anti-ROS capabilities, and the promotion of chondrogenesis. The enhancement of tissue adhesion was achieved by chemically modifying hyaluronic acid and chondroitin sulfate with o-nitrobenzene, enabling a covalent connection to the cartilage surface upon light irradiation. In vitro characterization revealed that GHC hydrogel facilitated chondrocyte adhesion, migration, and differentiation into cartilage. Additionally, GHC hydrogels demonstrated the ability to scavenge ROS in vitro and inhibit the production of inflammatory factors by chondrocytes. In the animal model of superficial cartilage injury, the hydrogel effectively promoted cartilage ECM regeneration and facilitated the interface integration between the host tissue and the material. These findings suggest that the multifunctional GHC hydrogels hold considerable promise as a strategy for cartilage defect repair. Statement of significanceSuperficial cartilage defects represent the most prevalent type of cartilage injury encountered in the clinic. Previous cartilage tissue engineering materials are only suitable for full-thickness cartilage defects or osteochondral defects. Here, we developed a multifunctional GHC hydrogel composed of gelatin, hyaluronic acid, and chondroitin sulfate, which are natural cartilage extracellular matrix components. The drug-free and cell-free hydrogel not only avoids immune rejection and drug toxicity, but also shows good mechanical properties and biocompatibility. More importantly, the GHC hydrogel could adhere tightly to the superficial cartilage defects and promote cartilage regeneration while protecting against oxidation. This natural ingredients and multifunctional hydrogel is a potential material for repairing superficial cartilage defects.

Accelerated cartilage regeneration through immunomodulation and enhanced chondrogenesis by an extracellular matrix hydrogel encapsulating Kartogenin

Articular cartilage is crucial for the functional integrity of joints yet vulnerable to a spectrum of injuries. The adverse immune microenvironment ensuing from injury, coupled with the intrinsic property of the tissue characterized by limited cellularity, poses a significant challenge to the reconstruction of cartilage defect. In this study, an extracellular matrix hydrogel derived from porcine small intestinal submucosa (SIS) with encapsulation of Kartogenin (KGN) has been designed for the cartilage repair and regeneration. The SIS hydrogel, which possessed a three-dimensional porous structure akin to the natural cartilage, has provided a scaffold essential for the progenitor cells engaged in the repair process and sustained release of KGN. As shown by in vitro experiments, the KGN could recruit host endogenous bone marrow-derived mesenchymal stem cells (BMSCs) and induce them to differentiate into chondrocytes, thus enabling in situ cartilage regeneration without cell transplantation. Notably, the bioactive component of SIS was further revealed to possess excellent immunomodulatory capacity to induce the phenotypic shift from M1 to M2 macrophages, which could enhance the chondrogenic differentiation of BMSCs indirectly. Additionally, in vivo experiments showed that the regenerated tissues of the composite SIS hydrogel group were close to the natural hyaline cartilage. Leveraging the combined effects of KGN and SIS hydrogel, this innovative composite material shows great potential as a biomaterial for effective cartilage repair and regeneration.

Synthetic Materials Used for Cartilage Regeneration in Recent Decade

Cartilage injury is considered the major cause of joint pain, swelling and dysfunction. Due to the cartilage tissue’s limited repair capacity, it’s very urgent and crucial to develop and investigate biomaterials to improve effective cartilage regeneration. Over the past decade, researchers focused of the design and preparation of a variety of synthetic materials. There synthetic scaffolds are expected to provide a favorable cellular microenvironment which is beneficial for cartilage regeneration. This review comprehensively reviews the major synthetic materials that have been recently applied in cartilage regeneration engineering, including a variety of polymers and a number of 3D printed materials. These materials have unique physicochemical structures and properties that can provide biocompatible three-dimensional porous structures, mimic the extracellular matrix environment in vivo, and promotes cell adhesion, proliferation, and differentiation. These properties all guide the orderly regeneration of cartilage tissues. Especially through the composite with bioactive molecules, nanomaterials, etc., these materials can also realize the controlled release of biological signals and precisely regulate cell behavior. In addition, by compositing natural polymers with synthetic polymers gives the hybrid scaffolds good bioactivity, it will also enhance their mechanical properties as well as the scaffold elasticity. These techniques allow researchers to develop the most ideal scaffold that perfectly mimics the natural cartilage environment.