Hydrogel composite scaffolds achieve recruitment and chondrogenesis in cartilage tissue engineering applications

Background The regeneration and repair of articular cartilage remains a major challenge for clinicians and scientists due to the poor intrinsic healing of this tissue. Since cartilage injuries are often clinically irregular, tissue-engineered scaffolds that can be easily molded to fill cartilage defects of any shape that fit tightly into the host cartilage are needed. Method In this study, bone marrow mesenchymal stem cell (BMSC) affinity peptide sequence PFSSTKT (PFS)-modified chondrocyte extracellular matrix (ECM) particles combined with GelMA hydrogel were constructed. Results In vitro experiments showed that the pore size and porosity of the solid-supported composite scaffolds were appropriate and that the scaffolds provided a three-dimensional microenvironment supporting cell adhesion, proliferation and chondrogenic differentiation. In vitro experiments also showed that GelMA/ECM-PFS could regulate the migration of rabbit BMSCs. Two weeks after implantation in vivo, the GelMA/ECM-PFS functional scaffold system promoted the recruitment of endogenous mesenchymal stem cells from the defect site. GelMA/ECM-PFS achieved successful hyaline cartilage repair in rabbits in vivo, while the control treatment mostly resulted in fibrous tissue repair. Conclusion This combination of endogenous cell recruitment and chondrogenesis is an ideal strategy for repairing irregular cartilage defects. Graphical Abstract

Effect of Type 1 Collagen Bioactive Material Scaffold on the Recovery of Sports-Caused Cartilage Injury

This study was aim to investigate the effect of type 1 collagen (Col I) bioactive scaffold on regeneration and repair of motor cartilage injury. Fifteen New Zealand rabbits were randomly divided into sham operation group (Sham group, only cartilage was exposed, no defect was made), model group Focal cortical dysplasias (FCD) group, cartilage defect model], and treatment group (Col I group, cartilage defect + Col I bioactive scaffold treatment). The cartilage tissue of each group was detected 16 weeks after the operation. Immunohistochemistry and Western Blot were adopted to detect the expression of cartilage related proteins in each group. The results showed that Col I bioactive scaffold could repair the gross morphology of cartilage defect, promote the regeneration and repair of chondrocytes in defect area, and reduce the mast cells in defect area. Western Blot detection of the expression of signal pathway marker proteins showed that expression of Wnt protein, β-catenin protein, and phosphofructokinase-1 (PFK-1) protein in the FCD group were significantly reduced than Sham group (P < 0.05), while the expression of phosphoenolpyruvate carboxykinase 1 (PEPCK1) protein was significantly increased (P < 0.05). Expression of Wnt protein, β-catenin protein, and PFK-1 protein in Col I group increased significantly versus FCD group (P < 0.05), while the expression of PEPCK1 protein significantly decreased (P < 0.05). In conclusion, Col I bioactive scaffolds could regenerate and repair cartilage defects, and the mechanism may be related to Wnt signaling pathway and glycolysis/gluconeogenesis pathway.

A highly porous type II collagen containing scaffold for the treatment of cartilage defects enhances MSC chondrogenesis and early cartilaginous matrix deposition.

A major challenge in cartilage tissue engineering (TE) is the development of instructive and biomimetic scaffolds capable of driving effective mesenchymal stem cell (MSC) chondrogenic differentiation and robust de novo...

Outcomes Associated With Osteochondral Allograft Transplantation in Dogs

The purpose of this study was to retrospectively characterize outcomes and complications associated with osteochondral allograft transplantation for treating chondral and osteochondral lesions in a group of client-owned dogs with naturally-occurring disease. Records were reviewed for information on signalment, treated joint, underlying pathology (e.g., osteochondritis dissecans; OCD), and type, size, and number of grafts used. Complications were classified as “trivial” if no treatment was provided, “non-surgical” if non-surgical treatment were needed, “minor surgical” if a minor surgical procedure such as pin removal were needed but the graft survived and function was acceptable, or “major” if the graft failed and revision surgery were needed. Outcomes were classified as unacceptable, acceptable, or full function. Thirty-five joints in 33 dogs were treated including nine stifles with lateral femoral condyle (LFC) OCD and 10 stifles with medial femoral condyle (MFC) OCD treated with osteochondral cylinders or “plugs.” There were 16 “complex” procedures of the shoulder, elbow, hip, stifle, and tarsus using custom-cut grafts. In total there were eight trivial complications, one non-surgical complication, two minor surgical complications, and five major complications for a total of 16/35 cases with complications. Accordingly, there were five cases with unacceptable outcomes, all of whom had major complications while the other 30 cases had successful outcomes. Of the 30 cases with successful outcomes, 15 had full function and 15 had acceptable function. Based on these subjective outcome assessments, it appears osteochondral allograft transplantation is a viable treatment option in dogs with focal or complex cartilage defects. However, no conclusions can be made regarding the inferiority or superiority of allograft transplantation in comparison to other treatment options based upon these data.

Treatment outcomes of patients with knee hyaline cartilage damages using osteoperforative methods

BACKGROUND: The treatment of traumatic and degenerative cartilage damage is one of the largest areas in orthopedic practice, and the therapy success remains limited. AIM: To analyze the results of surgical treatment of patients with traumatic and degenerative injuries of the knee joint hyaline cartilage using debridement and osteoperforative techniques, taking into account the time from the surgical intervention. MATERIALS AND METHODS: A statistical analysis was conducted on the treatment outcomes of servicemen with traumatic and degenerative damage in the knee joint articular hyaline cartilage. Patients underwent surgical treatment using osteoperforative techniques (abrasive chondroplasty, tunneling, and microfracturing) at the Clinic of Military Traumatology and Orthopedics of the S.M. Kirov Military Medical Academy from 2009 to 2019. The study relied on the data obtained from questioning the patients using the Knee Injury and Osteoarthritis Outcome Score (KOOS) and LKSS questionnaires. RESULTS: The result analyses using the KOOS and LKSS scales revealed significantly higher good results in the observed group in the postoperative period from 1 to 4 years than in the groups from 4 to 8 and more than 8 years (p = 0.004). No significant differences were determined in the treatment outcomes of the groups with resection and different osteoperforative methods. CONCLUSIONS: Treatment methods for hyaline cartilage defects, such as resection and osteoperforative, are technically simple with good treatment outcomes in patients with articular cartilage injuries from 1 to 4 years postoperative. Treatment outcome deterioration was noted in 48 years postoperative, regardless of the treatment method used, which is more significant in patients in 8 years postoperative.

Method Categorization of Stem Cell Therapy for Degenerative Osteoarthritis of the Knee: A Review

Current clinical applications of mesenchymal stem cell therapy for osteoarthritis lack consistency because there are no established criteria for clinical processes. We aimed to systematically organize stem cell treatment methods by reviewing the literature. The treatment methods used in 27 clinical trials were examined and reviewed. The clinical processes were separated into seven categories: cell donor, cell source, cell preparation, delivery methods, lesion preparation, concomitant procedures, and evaluation. Stem cell donors were sub-classified as autologous and allogeneic, and stem cell sources included bone marrow, adipose tissue, peripheral blood, synovium, placenta, and umbilical cord. Mesenchymal stem cells can be prepared by the expansion or isolation process and attached directly to cartilage defects using matrices or injected into joints under arthroscopic observation. The lesion preparation category can be divided into three subcategories: chondroplasty, microfracture, and subchondral drilling. The concomitant procedure category describes adjuvant surgery, such as high tibial osteotomy. Classification codes were assigned for each subcategory to provide a useful and convenient method for organizing documents associated with stem cell treatment. This classification system will help researchers choose more unified treatment methods, which will facilitate the efficient comparison and verification of future clinical outcomes of stem cell therapy for osteoarthritis.

Hydrogels with tunable modulus regulate chondrocyte microaggregates growth for cartilage repair

Chondrocyte spheroids in 3D hydrogel are more beneficial to improve their survival and maintain chondrogenic phenotype comparing to dissociated chondrocytes. However, in-situ inducing cell into spheroids rather than encapsulating spheroids in a hydrogel remains a tremendous challenge because of the limitations of biochemical and viscoelastic controllability for hydrogel. Herein, a hydrogel consisting of photo-crosslinkable chitosan methacrylate (CHMA) and semi-interpenetrating polyvinyl alcohol (PVA) is developed as a cell-responsive matrix with controllable viscoelastic properties. The proposed CHMA-PVA precursor preferentially exhibits a weak gel-like state with a storage modulus of 16.9 Pa, loss modulus of 13.0 Pa and yielding stain of 1%, which could allow chondrocyte to vigorously move and assemble but hinder their precipitation before crosslinking. The chondrocytes could form microaggregates within 8 h in vitro and keep high viability. Moreover, subcutaneous implantation experiments demonstrate that the CHMA/PVA hydrogels are biocompatible and degrade within five weeks in vivo. The cell-free hydrogels are further placed in cylindrical cartilage defects in the rabbit femoral condyle and examined 8 weeks postoperatively. Gross, histological and immunohistochemical analyses reveal a significant acceleration for the cartilage regeneration. These findings suggest that this novel cell adhesion-responsive and histo-compatible hydrogel is promising for cartilage regeneration.

Adipose Tissue-Derived Mesenchymal Stem Cells as a Potential Restorative Treatment for Cartilage Defects: A PRISMA Review and Meta-Analysis

Cartilage defects are a predisposing factor for osteoarthritis. Conventional therapies are mostly palliative and there is an interest in developing newer therapies that target the disease’s progression. Mesenchymal stem cells (MSCs) have been suggested as a promising therapy to restore hyaline cartilage to cartilage defects, though the optimal cell source has remained under investigation. A PRISMA systematic review was conducted utilising five databases (MEDLINE, EMBASE, Cochrane Library, Scopus, Web of Science) which identified nineteen human studies that used adipose tissue-derived MSC (AMSC)-based therapies, including culture-expanded AMSCs and stromal vascular fraction, to treat cartilage defects. Clinical, imaging and histological outcomes, as well as other relevant details pertaining to cartilage regeneration, were extracted from each study. Pooled analysis revealed a significant improvement in WOMAC scores (mean difference: −25.52; 95%CI (−30.93, −20.10); p < 0.001), VAS scores (mean difference: −3.30; 95%CI (−3.72, −2.89); p < 0.001), KOOS scores and end point MOCART score (mean: 68.12; 95%CI (62.18, 74.05)), thus showing improvement. The studies in this review demonstrate the safety and efficacy of AMSC-based therapies for cartilage defects. Establishing standardised methods for MSC extraction and delivery, and performing studies with long follow-up should enable future high-quality research to provide the evidence needed to bring AMSC-based therapies into the market.

Treating Full Depth Cartilage Defects with Intraosseous Infiltration of Plasma Rich in Growth Factors: An Experimental Study in Rabbits

Objective Intraarticular (IA) administration of platelet-rich plasma (PRP) has been proposed as a new strategy to halt osteoarthritis (OA) progression. In patients with severe OA, its potential is limited because it is unable to reach the subchondral bone, so a new strategy is needed, and intraosseous (IO) infiltration has been suggested. The purpose is to assess the impact of IA together with IO infiltration of plasma rich in growth factors (PRGF) in serum hyaluronic acid (HA) and type II collagen cleavage neoepitope (C2C) levels. Design A total of 32 rabbits were included in the study and randomly divided into 2 groups: control and treatment. A 4-mm chondral defect was created in the medial femoral condyle and IA followed by IO infiltration were performed. Serum C2C and HA levels were measured using enzyme-linked immunosorbent assay (ELISA) tests before infiltration and 28, 56, and 84 days post-infiltration. Results Significant lower C2C serum levels were obtained in treatment group (IA + IO infiltration of PRGF) at 84 days post-infiltration than in control group (IA infiltration of PRGF + IO infiltration of saline solution), while no significant differences between groups were reported at any other study times. Regarding HA, at 56 days post-infiltration, greater significant levels were seen in the treatment group. However, at 84 days post-infiltration, no significant differences were obtained, although lower levels were reported in the treatment group. Conclusions Despite inconclusive, the results suggest that the combination of IA and IO infiltration with PRGF may enhance cartilage and subchondral bone regeneration, but further studies are needed.