Articular Cartilage Regeneration Research Articles

Long-Term Culture Performance of a Polyelectrolyte Complex Microcapsule Platform for Hyaline Cartilage Repair.

Articular cartilage (AC) tissue repair and regeneration remains an ongoing challenge. One component of the challenge is the limited ability to scale an engineered cartilage graft to clinically relevant sizes while maintaining uniform properties. In this paper, we report on the evaluation of our polyelectrolyte complex microcapsule (PECM) platform technology as a technique for generating cartilage-like spherical modules. Bone marrow-derived mesenchymal stem cells (bMSCs) or primary articular chondrocytes were encapsulated within PECMs composed of methacrylated hyaluronan, collagen I, and chitosan. The formation of cartilage-like tissue in the PECMs over a 90-day culture was characterized. The results showed that chondrocytes exhibited superior growth and matrix deposition compared to either chondrogenically-induced bMSCs or a mixed PECM culture containing both chondrocytes and bMSCs. The chondrocyte-generated matrix filled the PECM and produced substantial increases in capsule compressive strength. The PECM system thus appears to support intracapsular cartilage tissue formation and the capsule approach promotes efficient culture and handling of these micro tissues. Since previous studies have proven the feasibility of fusing such capsules into large tissue constructs, the results suggest that encapsulating primary chondrocytes in PECM modules may be a viable route toward achieving a functional articular cartilage graft.

Bone Marrow Aspirate Concentrate versus Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells for Combined Cartilage Regeneration Procedure in Patients Undergoing High Tibial Osteotomy: A Systematic Review and Meta-Analysis.

Background and objectives: Cartilage regeneration using mesenchymal stem cells (MSCs) has been attempted to improve articular cartilage regeneration in varus knee osteoarthritis (OA) patients undergoing high tibial osteotomy (HTO). Bone marrow aspirate concentrate (BMAC) and human umbilical cord blood-derived MSCs (hUCB-MSCs) have been reported to be effective. However, whether BMAC is superior to hUCB-MSCs remains unclear. This systematic review and meta-analysis aimed to determine the clinical efficacy of cartilage repair procedures with BMAC or hUCB-MSCs in patients undergoing HTO. Materials and Methods: A systematic search was conducted using three global databases, PubMed, EMBASE, and the Cochrane Library, for studies in which the clinical outcomes after BMAC or hUCB-MSCs were used in patients undergoing HTO for varus knee OA. Data extraction, quality control, and meta-analysis were performed. To compare the clinical efficacy of BMAC and hUCB-MSCs, reported clinical outcome assessments and second-look arthroscopic findings were analyzed using standardized mean differences (SMDs) with 95% confidence intervals (CIs). Results: The present review included seven studies of 499 patients who received either BMAC (BMAC group, n = 169) or hUCB-MSCs (hUCB-MSC group, n = 330). Improved clinical outcomes were found in both BMAC and hUCB-MSC groups; however, a significant difference was not observed between procedures (International Knee Documentation Committee score; p = 0.91, Western Ontario and McMaster Universities OA Index; p = 0.05, Knee Society Score (KSS) Pain; p = 0.85, KSS Function; p = 0.37). On second-look arthroscopy, the hUCB-MSC group showed better International Cartilage Repair Society Cartilage Repair Assessment grade compared with the BMAC group (p < 0.001). Conclusions: Both BMAC and hUCB-MSCs with HTO improved clinical outcomes in varus knee OA patients, and there was no difference in clinical outcomes between them. However, hUCB-MSCs were more effective in articular cartilage regeneration than BMAC augmentation.

Functional Mechanism of Mesenchymal Stem Cell-Derived Exosomes in Articular Cartilage Regeneration

As the aging of the population, a chronic degenerative joint disease - Osteoarthritis (OA), its incidence and severity are increasing. Compared with cells, the immunogenicity of the exon is low and the immunomodulatory performance is excellent. Various types of mesenchymal stem cell-derived exosomes (MSC-EXOs) are now being used to treat cartilage injury and disease as target drugs or delivery vehicles. A thorough examination of the existing evidence is required in light of the emerging evidence on the effective mechanism and method of MSC-EXOs in OA. This article reviews the specific mechanism and latest research progress of MSCs derived exosomes in OA treatment. It mainly summarizes three mechanisms of action of exosomes: a. Enhancing extracellular matrix (ECM) and preventing cartilage degradation; b. Promoting chondrocyte migration, proliferation, migration, and inhibiting chondrocyte apoptosis, c. Influencing immune protection or immune destruction signals. In addition, the difficulties of exosomes in the clinical treatment of OA are briefly reviewed, with the hope of providing ideas for developing biomaterials scaffolds and clinical treatment of MSC-EXOs.

Photocrosslinkable, Injectable Locust Bean Gum Hydrogel Induces Chondrogenic Differentiation of Stem Cells for Cartilage Regeneration.

Due to the limited therapeutic efficacy of current treatments, articular cartilage regeneration is still challenging work. Scaffold-based tissue engineering provides a promising strategy for cartilage regeneration, but most scaffolds are limited by poor mechanical properties or unfavorable biocompatibility. Here, a novel photocrosslinkable, injectable locust bean gum (LBG)-methacrylate (MA) hydrogel is reported as a biomimetic extracellular matrix (ECM) for cartilage repair with minimal invasive operation. LBG-MA hydrogels show controllable degradation rate and improve mechanical properties and excellent biocompatibility. More importantly, LBG-MA hydrogel significantly induces bone mesenchymal stem cells to chondrogenic differentiation in vitro, as evidenced by high accumulation of cartilage-specific ECM components glycosaminoglycan and upregulated expression of key chondrogenic genes (collagen type II, aggrecan, and sex determining region Y-box9). Besides, the hydrogel is injectable, which can be in situ crosslinked via UV irradiation. Further, the photocrosslinkable hydrogels accelerate cartilage healing in vivo after 8 weeks of therapy. A strategy is provided here for photocrosslinkable, injectable, biodegradable scaffold fabrication based on native polysaccharide polymer for minimal invasive cartilage repair.

Bipolar Lesions of the Knee Are Associated With Inferior Clinical Outcome Following Articular Cartilage Regeneration. A Propensity Score-Matched Analysis Including 238 Patients of the German Cartilage Registry (KnorpelRegister DGOU)

To determine whether bipolar lesions (BL) are associated with inferior clinical outcome following articular cartilage regeneration (CR) compared to unipolar lesions (UL). A registry-based study, including patients undergoing isolated CR for focal knee cartilage lesions was performed. Lesions were considered UL or BL depending on the opposing cartilage. Propensity score matching was applied to eliminate potential confounders. Two groups comprising 119 patients with similar baseline characteristics were matched. The Knee Injury and Osteoarthritis Outcome Score (KOOS) at baseline, 6, 12, 24, and 36 months following CR served as primary outcome measure. KOOS improvement, reaching the minimal clinically important difference (MCID), KOOS subcomponents, and failure rates were calculated. Autologous chondrocyte implantation (ACI) was the most frequently performed procedure in both groups with 63.0% (BL) and 46.6% (UL). There was a significant difference regarding KOOS at 24 months between UL (76.39 ± 14.96) and BL (69.83 ± 18.83; P= .028), which did not exceed the threshold of MCID. No significant difference was detected at any other follow-up. KOOS improvement from baseline was lower in the BL group at all follow-ups and peaked at 36 months in both groups (UL [26.00 ± 16.12] vs. BL [16.63 ± 17.29]; P= .024). The failure rate in the BL group was higher at 8.2% (9/110) compared to the UL group at 3.9% (4/98) (P= .256). BL were associated with worse clinical outcome 2 years following CR compared to UL. However, both groups showed an ongoing clinical improvement up to 3 years postoperatively and a low failure rate. While inferior clinical improvement and a lower clinical response rate may be expected in BL patients, the observed differences do not justify excluding these patients from CR. Level III, retrospective comparative prognostic trial.

Hierarchical porous ECM scaffolds incorporating GDF-5 fabricated by cryogenic 3D printing to promote articular cartilage regeneration

BackgroundIn recent years, there has been significant research progress on in situ articular cartilage (AC) tissue engineering with endogenous stem cells, which uses biological materials or bioactive factors to improve the regeneration microenvironment and recruit more endogenous stem cells from the joint cavity to the defect area to promote cartilage regeneration.MethodIn this study, we used ECM alone as a bioink in low-temperature deposition manufacturing (LDM) 3D printing and then successfully fabricated a hierarchical porous ECM scaffold incorporating GDF-5.ResultsComparative in vitro experiments showed that the 7% ECM scaffolds had the best biocompatibility. After the addition of GDF-5 protein, the ECM scaffolds significantly improved bone marrow mesenchymal stem cell (BMSC) migration and chondrogenic differentiation. Most importantly, the in vivo results showed that the ECM/GDF-5 scaffold significantly enhanced in situ cartilage repair.ConclusionIn conclusion, this study reports the construction of a new scaffold based on the concept of in situ regeneration, and we believe that our findings will provide a new treatment strategy for AC defect repair.

3D BIOPRINTING OF ARTICULAR CARTILAGE FOR IN VIVO APPLICATION

3D printing and Bioprinting technologies are becoming increasingly popular in surgery to provide a solution for the regeneration of healthy tissues. The aim of our project is the regeneration of articular cartilage via bioprinting means, to manage isolated chondral defects.Chrondrogenic hydrogel (chondrogel: GelMa + TGF-b3 and BMP6) was prepared and sterilised in our lab following our standard protocols. Human adipose-derived mesenchymal stem cells were harvested from the infrapatellar fat pad of patients undergoing total knee joint replacements and incorporated in the hydrogel according to our published protocols. The chondrogenic properties of the chondrogel have been tested (histology, immunohistochemistry, PCR, immunofluorescence, gene analysis and 2nd harmonic generation microscopy) in vitro and in an ex-vivo model of human articular defect and compared with standard culture systems where the growth factors are added to the media at repeated intervals.The in-vitro analysis showed that the formation of hyaline cartilage pellet was comparable between the two strategies, with a similar metabolic activity of the cells. These results have been confirmed in the ex-vivo model: hyaline-like cartilage was observed within the chondral defect in both the chondrogel group and the control group after 28 days in culture.The use of bioprinting techniques in vivo requires the ability of stem cells to access growth factors directly in the environment they are in, as opposed to in vitro techniques where these factors are provided externally at recurrent intervals. This study showed the successful strategy of incorporating chondrogenic growth factors for the formation of hyaline-like cartilage in vitro and in an ex-vivo model of chondral loss.The incorporation of chondrogenic growth factors in a hydrogel is a possible strategy for articular cartilage regeneration.

M2 macrophages-derived exosomes combined with acellular cartilage matrix scaffolds promote osteochondral regeneration via modulatory microenvironment

Articular cartilage (AC) regeneration has always been a difficult problem for clinicians. Anti-inflammatory (M2) macrophages have anti-inflammatory and tissue repair effects. Exosomes are reported to have multiple complicated biological functions. It has been shown that M2 macrophages-derived exosomes (M2D-Exo) can influence the course of certain diseases, but their effect on the repair of cartilage defects has not been reported. The aim of this study was to verify whether M2D-Exo could enhance the repair of acellular cartilage extracellular matrix (ACECM) scaffolds. Here, we characterized the ACECM scaffolds and identified the M2D-Exo by transmission electron microscopy (TEM), Western blotting (WB), and nanoparticle tracking analysis (NTA). In vitro, the results showed that M2D-Exo could promote the migration, proliferation and chondrogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs). It was also found that M2D-Exo could reduce the expression of proinflammatory factors and promote M2 polarization, which ultimately protected chondrocytes and inhibited chondrocyte apoptosis. In vivo results confirmed that M2D-Exo could promote the repair effect of ACECM scaffolds, promote osteochondral regeneration and regulate the joint cavity inflammatory microenvironment. In conclusion, this study confirms that M2D-Exo can be used as a new therapeutic strategy for osteochondral regenerative repair.

Perspective in Achieving Stratified Articular Cartilage Repair Using Zonal Chondrocytes.

Articular cartilage is composed of superficial, medial, and deep zones, which endow the tissue with biphasic mechanical properties to withstand shearing force and compressional loading. The tissue has very limited self-healing capacity once it is damaged due to its avascular nature. To prevent the early onset of osteoarthritis, surgical intervention is often needed to repair the injured cartilage. Current noncell-based and cell-based treatments focus on the regeneration of homogeneous cartilage to achieve bulk compressional properties without recapitulating the zonal matrix and mechanical properties, and often oversight in aiding cartilage integration between host and repair cartilage. It is hypothesized that achieving zonal architecture in articular cartilage tissue repair could improve the structural and mechanical integrity and thus the life span of the regenerated tissue. Engineering stratified cartilage constructs using zonal chondrocytes have been hypothesized to improve the functionality and life span of the regenerated tissues. However, stratified articular cartilage repair has yet to be realized to date due to the lack of an efficient zonal chondrocyte isolation method and an expansion platform that would allow both cell propagation and phenotype maintenance. Various attempts and challenges in achieving stratified articular cartilage repair in a clinical setting are evaluated. In this review, different perspectives on achieving stratified articular cartilage repair using zonal chondrocytes are described. The effectiveness of different zonal chondrocyte isolation and zonal chondrocyte phenotype maintenance methodologies during expansion are compared, with the focus on recent advancements in zonal chondrocyte isolation and expansion that could present a possible strategy to overcome the limitation of applying zonal chondrocytes to facilitate zonal architecture development in articular cartilage regeneration. Impact Statement The zonal properties of articular cartilage contribute to the biphasic mechanical properties of the tissues. Recapitulation of the zonal architecture in regenerated articular cartilage has been hypothesized to improve the mechanical integrity and life span of the regenerated tissue. This review provides a comprehensive discussion on the current state of research relevant to achieving stratified articular cartilage repair using zonal chondrocytes from different perspectives. This review further elaborates on a zonal chondrocyte production pipeline that can potentially overcome the current clinical challenges and future work needed to realize stratified zonal chondrocyte implantation in a clinical setting.

Incorporation of kartogenin and silk fibroin scaffolds promotes rat articular cartilage regeneration through enhancement of antioxidant functions.

Treating articular cartilage defects in patients remains a challenging task due to the absence of blood vessels within the cartilage tissue. The regenerative potential is further compromised by an imbalance between anabolism and catabolism, induced by elevated levels of reactive oxygen species. However, the advent of tissue engineering introduces a promising strategy for cartilage regeneration, offering viable solutions such as mechanical support and controlled release of chondrogenic molecules or cytokines. In this study, we developed an antioxidant scaffold by incorporating natural silk fibroin (SF) and kartogenin (KGN)-loaded liposomes (SF-Lipo@KGN). The scaffold demonstrated appropriate pore size, connectivity, and water absorption and the sustained release of KGN was achieved through the encapsulation of liposomes. In vitro experiments revealed that the SF-Lipo@KGN scaffolds exhibited excellent biocompatibility, as evidenced by enhanced cell adhesion, migration, and proliferation of chondrocytes. The SF-Lipo@KGN scaffolds were found to stimulate cartilage matrix synthesis through the activation of the nuclear factor erythroid-2-related factor 2/heme oxygenase-1 antioxidant signaling pathway. In vivo experiments demonstrated the effective promotion of articular cartilage regeneration by the SF-Lipo@KGN scaffolds, which enhanced extracellular matrix anabolism and restored the intrinsic redox homeostasis. Overall, this study successfully developed biomimetic KGN-loaded scaffolds that restore cartilage redox homeostasis, indicating promising prospects for cartilage tissue engineering.

Effects of Electrical Stimulation on Articular Cartilage Regeneration with a Focus on Piezoelectric Biomaterials for Articular Cartilage Tissue Repair and Engineering.

There is increasing evidence that chondrocytes within articular cartilage are affected by endogenous force-related electrical potentials. Furthermore, electrical stimulation (ES) promotes the proliferation of chondrocytes and the synthesis of extracellular matrix (ECM) molecules, which accelerate the healing of cartilage defects. These findings suggest the potential application of ES in cartilage repair. In this review, we summarize the pathogenesis of articular cartilage injuries and the current clinical strategies for the treatment of articular cartilage injuries. We then focus on the application of ES in the repair of articular cartilage in vivo. The ES-induced chondrogenic differentiation of mesenchymal stem cells (MSCs) and its potential regulatory mechanism are discussed in detail. In addition, we discuss the potential of applying piezoelectric materials in the process of constructing engineering articular cartilage, highlighting the important advances in the unique field of tissue engineering.

Tetrahedral framework nucleic acids enhance the chondrogenic potential of human umbilical cord mesenchymal stem cells via the PI3K/AKT axis.

The field of regenerative medicine faces a notable challenge in terms of the regeneration of articular cartilage. Without proper treatment, it can lead to osteoarthritis. Based on the research findings, human umbilical cord mesenchymal stem cells (hUMSCs) are considered an excellent choice for regenerating cartilage. However, there is still a lack of suitable biomaterials to control their ability to self-renew and differentiate. To address this issue, in this study using tetrahedral framework nucleic acids (tFNAs) as a new method in an in vitro culture setting to manage the behaviour of hUMSCs was proposed. Then, the influence of tFNAs on hUMSC proliferation, migration and chondrogenic differentiation was explored by combining bioinformatics methods. In addition, a variety of molecular biology techniques have been used to investigate deep molecular mechanisms. Relevant results demonstrated that tFNAs can affect the transcriptome and multiple signalling pathways of hUMSCs, among which the PI3K/Akt pathway is significantly activated. Furthermore, tFNAs can regulate the expression levels of multiple proteins (GSK3β, RhoA and mTOR) downstream of the PI3K-Akt axis to further enhance cell proliferation, migration and hUMSC chondrogenic differentiation. tFNAs provide new insight into enhancing the chondrogenic potential of hUMSCs, which exhibits promising potential for future utilization within the domains of AC regeneration and clinical treatment.

STAT3 promotes a youthful epigenetic state in articular chondrocytes.

Epigenetic mechanisms guiding articular cartilage regeneration and age-related disease such as osteoarthritis (OA) are poorly understood. STAT3 is a critical age-patterned transcription factor highly active in fetal and OA chondrocytes, but the context-specific role of STAT3 in regulating the epigenome of cartilage cells remain elusive. In this study, DNA methylation profiling was performed across human chondrocyte ontogeny to build an epigenetic clock and establish an association between CpG methylation and human chondrocyte age. Exposure of adult chondrocytes to a small molecule STAT3 agonist decreased DNA methylation, while genetic ablation of STAT3 in fetal chondrocytes induced global hypermethylation. CUT&RUN assay and subsequent transcriptional validation revealed DNA methyltransferase 3 beta (DNMT3B) as one of the putative STAT3 targets in chondrocyte development and OA. Functional assessment of human OA chondrocytes showed the acquisition of progenitor-like immature phenotype by a significant subset of cells. Finally, conditional deletion of Stat3 in cartilage cells increased DNMT3B expression in articular chondrocytes in the knee joint in vivo and resulted in a more prominent OA progression in a post-traumatic OA (PTOA) mouse model induced by destabilization of the medial meniscus (DMM). Taken together these data reveal a novel role for STAT3 in regulating DNA methylation in cartilage development and disease. Our findings also suggest that elevated levels of active STAT3 in OA chondrocytes may indicate an intrinsic attempt of the tissue to regenerate by promoting a progenitor-like phenotype. However, it is likely that chronic activation of this pathway, induced by IL-6 cytokines, is detrimental and leads to tissue degeneration.

Smart Biomaterials for Articular Cartilage Repair and Regeneration

AbstractArticular cartilage defects bring about disability and worldwide socioeconomic loss, therefore, articular cartilage repair and regeneration is recognized as a global issue. However, due to its avascular and nearly acellular characteristic, cartilage tissue regeneration ability is limited to some extent. Despite the availability of various treatment methods, including palliative drugs and surgical regenerative therapy, articular cartilage repair and regeneration still face major challenges due to the lack of appropriate methods and materials. Smart biomaterials can regulate cell behavior and provide excellent tissue repair and regeneration microenvironment, thus inducing articular cartilage repair and regeneration. This process is adjusted by controlling drug/bioactive factors release via responding to exogenous/endogenous stimuli, tailoring materials’ structure and function similar to native cartilage or providing physiochemical and physical signaling factors. Herein, smart biomaterials, recently applied in articular cartilage repair and regeneration, are elaborated from two aspects: smart drug release system and smart scaffolds. Furthermore, articular cartilage and its defects and advanced manufacturing techniques of smart biomaterials are discussed in brief. Finally, perspectives for smart biomaterials used in articular cartilage repair and regeneration are presented and the clinical translation of smart biomaterials is emphasized.

Intra-articular injection of human umbilical cord-derived mesenchymal stem cells in sheep models of meniscectomy-induced osteoarthritis: An experimental study

Introduction: Autologous mesenchymal stem cells (MSC) implantation suspended in hyaluronic acid (HA) has been proven to delay worsening of articular cartilage degeneration in the knee joint. This has been the treatment of choice for young patients with knee osteoarthritis (KOA); however, it is associated with morbidities such as requirement of multiple procedures, donor site morbidity and failure in achieving cultured cells with chondrogenic properties. Our study investigates the possibility of direct intra articular injection of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) for sheep models of meniscectomy-induced osteoarthritis. Methods: Twelve sheeps with the same characteristics was osteoarthritically induced with lateral meniscectomy and a series of routine exercise. Those sheep were divided into four groups with 3 sheep each. The groups are the control group, intra articular HA (hyalgan G-F 20; Synvisc®) injection group, intra articular hUC-MSCs group, intra articular hUC-MSCs suspended in HA group. The sheeps were sacrificed four weeks post-treatment for gross pathology and histopathology graded according to the Osteoarthritic Research Society International (OARSI) system. Results: The intra articular hUC-MSCs suspended in HA group showed better gross pathology and histopathology grade compared to control groups (p&lt;0.05) according to the OARSI system. The hUC-MSCs suspended in HA group microscopically showed superior chondrocyte number and varying degrees of cellular regeneration of articular cartilage. Conclusion: The use of intra articular hUC-MSCs suspended in HA is an option in treating KOA. Its efficacy in articular cartilage regeneration would be further explained in clinical trials.

An advanced biphasic porous and injectable scaffold displays a fine balance between mechanical strength and remodeling capabilities essential for cartilage regeneration.

An important challenge in tissue engineering is the regeneration of functional articular cartilage (AC). In the field, biomimetic hydrogels are being extensively studied as scaffolds that recapitulate microenvironmental features or as mechanical supports for transplanted cells. New advanced hydrogel formulations based on salmon methacrylate gelatin (sGelMA), a cold-adapted biomaterial, are presented in this work. The psychrophilic nature of this biomaterial provides rheological advantages allowing the fabrication of scaffolds with high concentrations of the biopolymer and high mechanical strength, suitable for formulating injectable hydrogels with high mechanical strength for cartilage regeneration. However, highly intricate cell-laden scaffolds derived from highly concentrated sGelMA solutions could be deleterious for cells and scaffold remodeling. On this account, the current study proposes the use of sGelMA supplemented with a mesophilic sacrificial porogenic component. The cytocompatibility of different sGelMA-based formulations is tested through the encapsulation of osteoarthritic chondrocytes (OACs) and stimulated to synthesize extracellular matrix (ECM) components in vitro and in vivo. The sGelMA-derived scaffolds reach high levels of stiffness, and the inclusion of porogens impacts positively the scaffold degradability and molecular diffusion, improved fitness of OACs, increased the expression of cartilage-related genes, increased glycosaminoglycan (GAG) synthesis, and improved remodeling toward cartilage-like tissues. Altogether, these data support the use of sGelMA solutions in combination with mammalian solid gelatin beads for highly injectable formulations for cartilage regeneration, strengthening the importance of the balance between mechanical properties and remodeling capabilities.

Bone marrow stem cells incubated with ellipticine regenerate articular cartilage by attenuating inflammation and cartilage degradation in rabbit model.

Ellipticine (Ellip.) was recently reported to have beneficial effects on the differentiation of adipose-derived stem cells into mature chondrocyte-like cells. On the other hand, no practical results have been derived from the transplantation of bone marrow stem cells (BMSCs) in a rabbit osteoarthritis (OA) model. This study examined whether autologous BMSCs incubated with ellipticine (Ellip.+BMSCs) could regenerate articular cartilage in rabbit OA, a model similar to degenerative arthritis in human beings. A portion of rabbit articular cartilage was surgically removed, and Ellip.+BMSCs were transplanted into the lesion area. After two and four weeks of treatment, the serum levels of proinflammatory cytokines, i.e., tumor necrosis factor α (TNF-α) and prostaglandin E2 (PGE2), were analyzed, while macroscopic and micro-computed tomography (CT) evaluations were conducted to determine the intensity of cartilage degeneration. Furthermore, immuno-blotting was performed to evaluate the mitogen-activated protein kinases, PI3K/Akt, and nuclear factor-κB (NF-κB) signaling in rabbit OA models. Histological staining was used to confirm the change in the pattern of collagen and proteoglycan in the articular cartilage matrix. The transplantation of Ellip.+BMSCs elicited a chondroprotective effect by reducing the inflammatory factors (TNF-α, PGE2) in a time-dependent manner. Macroscopic observations, micro-CT, and histological staining revealed articular cartilage regeneration with the downregulation of matrix-metallo proteinases (MMPs), preventing articular cartilage degradation. Furthermore, histological observations confirmed a significant boost in the production of chondrocytes, collagen, and proteoglycan compared to the control group. Western blotting data revealed the downregulation of the p38, PI3K-Akt, and NF-κB inflammatory pathways to attenuate inflammation. The transplantation of Ellip.+BMSCs normalized the OA condition by boosting the recovery of degenerated articular cartilage and inhibiting the catabolic signaling pathway.

Thermosensitive hydrogel for cartilage regeneration via synergistic delivery of SDF-1α like polypeptides and kartogenin

Regeneration of injured articular cartilage is limited by low early-stage recruitment of stem cells and insufficient chondrogenic differentiation. Hydrogels are widely used to repair cartilage because they have excellent mechanical and biological properties. In this study, a dual drug-loaded thermosensitive hydroxypropyl chitin hydrogel (HPCH) system was prepared to release stromal-derived factor-1α-like polypeptides (SDFP) and kartogenin (KGN) for stem-cell recruitment and chondrogenic differentiation. The hydrogel had a network structure that promoted cell growth and nutrient exchange. Moreover, it was temperature sensitive and suitable for filling irregular defects. The system showed good biocompatibility in vitro and promoted stem-cell recruitment and chondrogenic differentiation. Furthermore, it reduced chondrocyte catabolism under inflammatory conditions. Animal experiments demonstrated that the dual-drug hydrogel systems can promote the regeneration of articular cartilage in rats. This study confirmed that an HPCH system loaded with KGN and SDFP could effectively repair articular cartilage defects and represents a viable treatment strategy.

Computational model of articular cartilage regeneration induced by scaffold implantation in vivo

Computational models allow to explain phenomena that cannot be observed through an animal model, such as the strain and stress states which can highly influence regeneration of the tissue. For this purpose, we have developed a simulation tool to determine the mechanical conditions provided by the polymeric scaffold. The computational model considered the articular cartilage, the subchondral bone, and the scaffold. All materials were modeled as poroelastic, and the cartilage had linear-elastic oriented collagen fibers. This model was able to explain the remodeling process that subchondral bone goes through, and how the scaffold allowed the conditions for cartilage regeneration. These results suggest that the use of scaffolds might lead the cartilaginous tissue growth in vivo by providing a better mechanical environment. Moreover, the developed computational model demonstrated to be useful as a tool prior experimental in vivo studies, by predicting the possible outcome of newly proposed treatments allowing to discard approaches that might not bring good results.

Effects of Intra-articular Platelet Rich Plasma on Cartilage Thickness, Clinical and Functional Outcomes in Knee Osteoarthritis.

Osteoarthritis of the kneeis one of the most common degenerative diseases and the fourth leading cause of years lived with disability at the global level. This study assessed the efficacy of platelet-rich plasma (PRP) in osteoarthritis of knees as to changes in cartilage thickness and clinical and functional outcomes. Thirty participants with Kellgren-Lawrence grade two and grade three osteoarthritis knee who satisfied the inclusion and exclusion criteria were enrolled in this prospective interventional study after taking written informed consent. Each participant received three doses of two ml intraarticular platelet-rich plasma at an interval of seven days. Clinical assessment was determined using the Visual Analogue Scale (VAS) and Knee Osteoarthritis Outcome Score (KOOS) on Day 0, Day 90, and Day 180. Cartilage thickness (femoral and trochlear cartilage) was measured pre (Day 0) and post-PRP (Day 180) under ultrasound guidance. The mean VAS score for pain was 7.4 before treatment which changed to 5.3 (p= <0.0001) on Day 90 and 3.37 (p= <0.0001) on Day 180 post-PRP. The mean total KOOS was 19.16 ± 10.73 before treatment which improved to 37.42 ± 9.88 (p= <0.0001) and 49.98 ± 8.82 (p= <0.0001) at 90 days, and 180 days post-injection, respectively. The mean cartilage thickness (femoral and trochlear cartilage) improved from baseline (day 0) to final follow-up on day 180, which was statistically significant and implied cartilage repair following PRP administration. This study supports the efficacy of PRP in the management of osteoarthritis knee by improvement in pain, joint stiffness, and activities of daily living, as well as aids in the repair and regeneration of articular cartilage.