Hyaline-like Cartilage Repair Research Articles

Repair of articular cartilage defects with a novel injectablein situforming material in a canine model

We developed an ultra-purified in situ forming gel as an injectable delivery vehicle of bone marrow stromal cells (BMSCs). Our objective was to assess reparative tissues treated with autologous BMSCs implanted using the injectable implantation system into osteochondral defects in a canine model. Forty-eight osteochondral defects in the patella groove of the knee joint were created in 12 adult beagle dogs (two defects in each knee). The defects were divided into a defect group (n = 16), an acellular novel material implantation (material) group (n = 16), and a BMSCs implantation using the current vehicle system (material with BMSCs) group (n = 16). The reparative tissues at 16 weeks postoperatively were assessed through gross, histological, and mechanical analyses. The reparative tissues of the material with BMSCs group were substituted with firm and smooth hyaline-like cartilage tissue that was perfectly integrated into the host tissues. This treatment group obviously enhanced the subchondral bone reconstruction. The compressive modulus of the reparative tissues was significantly higher in the material with BMSCs group than the other groups. This study demonstrated that the implantation of BMSCs using our novel in situ forming material induced a mature hyaline-like cartilage repair of osteochondral defects in a canine model.

A Cell-free Scaffold-based Cartilage Repair Provides Improved Function Hyaline-like Repair at One year

Bone marrow stimulation techniques in cartilage repair such as drilling are limited by the formation of fibrous to hyaline-like repair tissue. It has been suggested such techniques can be enhanced by covering the defect with scaffolds. We present an innovative approach using a polyglycolic acid (PGA)-hyaluronan scaffold with platelet-rich-plasma (PRP) in drilling. We asked whether (1) PRP immersed in a cell-free PGA-hyaluronan scaffold improves patient-reported 1-year outcomes for the Knee injury and Osteoarthritis Score (KOOS), and (2) implantation of the scaffold in combination with bone marrow stimulation leads to the formation of hyaline-like cartilage repair tissue. We reviewed 52 patients who had arthroscopic implantation of the PGA-hyaluronan scaffold immersed with PRP in articular cartilage defects of the knee pretreated with Pridie drilling. Patients were assessed by KOOS. At 9 months followup, histologic staining was performed in specimens obtained from five patients to assess the repair tissue quality. The KOOS subscores improved for pain (55 to 91), symptoms (57 to 88), activities of daily living (69 to 86), sports and recreation (36 to 70), and quality of life (38 to 73). The histologic evaluation showed a homogeneous hyaline-like cartilage repair tissue. The cell-free PGA-hyaluronan scaffold combined with PRP leads to cartilage repair and improved patient-reported outcomes (KOOS) during 12 months of followup. Histologic sections showed morphologic features of hyaline-like repair tissue. Long-term followup is needed to determine if the cartilage repair tissue is durable. Level IV, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.

Prospective evaluation of serum biomarker levels and cartilage repair by autologous chondrocyte transplantation and subchondral drilling in a canine model

IntroductionThe purpose of this study was to evaluate serum chondroitin sulfate (CS) and hyaluronic acid (HA) levels and the capability of cartilage repair of full-thickness cartilage defects after treatment with two different fundamental surgical techniques: autologous chondrocyte transplantation (AC) and subchondral drilling (SD).MethodsA 4-mm-diameter full-thickness cartilage defect was created in each of 10 skeletally mature male outbred dogs. The dogs were randomly separated into two groups. Groups A and B were treated with AC and SD, respectively. An evaluation was made at the 24th week of the experiment. Serum was analyzed prospectively – preoperatively and at 6-week intervals – for CS and HA levels by enzyme-linked immunosorbent assay (ELISA) and ELISA-based assays, respectively.ResultsThe cartilage repair assessment score (median ± standard deviation) of group A (9.5 ± 2.5) was significantly higher than that of group B (2.5 ± 1.3) (P < 0.05). Group A also demonstrated a better quality of hyaline-like cartilage repair. Prospective analysis of serum WF6 and HA levels between the two groups did not show any significant difference. Serum WF6 levels at the 24th week of the experiment had a negative correlation (r = -0.69, P < 0.05) with the cartilage repair assessment score, whereas serum HA levels tended to correlate positively (r = 0.46, 0.1 <P < 0.05).ConclusionsAC treatment provides superior results to SD treatment, according to morphology, histology, and cartilage marker levels. AC treatment demonstrated a smoother surface, less fissure, better border integration, and a more reliable outcome of repairing cartilage. Moreover, a decreasing level of serum WF6, which correlated with good quality of the repairing tissue at the end of the follow-up period, was found predominantly in the AC group. Serum WF6 therefore should be further explored as a sensitive marker for the noninvasive therapeutic evaluation of cartilage repair procedures.

Regional gene therapy for full‐thickness articular cartilage lesions using naked DNA with a collagen matrix

A novel gene therapy approach for treating damaged cartilage is proposed that involves placing endotoxin-free cDNA containing the gene for bone morphogenetic protein-2 (BMP-2) in type I collagen sponges and then transferring the naked plasmid DNA construct to the injury site. A full-thickness cartilaginous defect in rabbits implanted with plasmid containing a marker gene (beta-galactosidase) showed expressed protein as detected by immunostaining. At 1 week postimplantation, mesenchymal cells subjacent to the defect had incorporated the implanted naked plasmid DNA and, once transfected, served as local bioreactors, transiently producing the gene product. Plasmids containing the gene for BMP-2 implanted in collagen sponges in cartilage lesions stimulated hyalinelike articular cartilage repair at 12 weeks postimplantation, nearly equivalent in quality to that induced by collagen sponges with recombinant BMP-2 protein. Our approach circumvents the risks of inflammation and immunogenic response associated with the use of viral vectors. Naked plasmid DNA as a vehicle for transferring therapeutic genes has been shown to be effective in a therapeutic model within rabbit articular cartilage and appears to be safe and cost effective.

Osteogenic Protein-1 in Knee Arthritis and Arthroplasty

The use of graft materials to restore bone stock and promote healing and implant stabilization is a crucial part of total knee arthroplasty, especially in revision surgery. Recent research has centered on the use of osteoinductive materials to promote bone formation. Osteogenic proteins are members of a superfamily of proteins called transforming growth factor-beta that, either alone or in combination with other regulatory molecules, induce new bone formation. The cloning and genetic expression of recombinant human osteogenic proteins has led to production of quantities sufficient for their clinical use. Recombinant human osteogenic protein-1 has been combined with bone-derived Type I collagen for delivery to an implant site. Preclinical studies have shown that the osteoinductive capacity of autograft and allograft bone and bone graft substitute materials can be notably improved with the addition of osteogenic protein-1. The use of this protein consistently improved the amount and rate of new bone formation compared with graft alone, resulting in earlier graft incorporation and consolidation. In addition, because osteogenic proteins are chondrogenic, they also may have a role in the treatment of cartilage injury and degeneration. Osteogenic protein-1 has been shown to induce hyalinelike cartilage repair of full thickness osteochondral defects in animal models with no degradation of the tissue with time. Although no detailed clinical studies in knee surgery have been reported with the use of osteogenic protein-1, in anecdotal cases its use alone and with bone graft materials indicate results consistent with those obtained in preclinical studies.

Chondrocyte transplantation

Autologous chondrocyte transplantation (ACT) provides a durable hyaline repair tissue in correctly selected indications. Autologous chondrocyte transplantation is indicated for full-thickness, weight-bearing condyle injuries and injuries to the trochlea of the femur. ACT results in reproducibly satisfactory results with return to high-level activities including sports in over 90% of the patients. Second-look arthroscopies demonstrate tissue fills wth biopsies showing hyaline-like cartilage repair. Hyaline cartilage repair is critical because this has been shown clinically to give long standing results with follow-up at 2 to 9 years. As technical refinements improve, and rehabilitation protocols, results for injuries to the patellar and the tibia will improve. At this time the response to treating bipolar focal chondral injuries is unknown and not recommended.