Subchondral drillings for articular cartilage defects usually result in fibrocartilage repair, which is inferior biomechanically compared to hyaline cartilage. We postulate that intra-articular injections with autologous marrow-derived stem cells (MSC) and hyaluronic acid (HA) can improve the quality of repair cartilage. We tested this hypothesis in a goat model by creating an articular cartilage defect in the stifle joint and conducted subchondral drillings. The animals were divided into three groups: Group A (control) no injections, Group B (HA) weekly injection of 1 ml sodium hyaluronate for three weeks, Group C (HA+MSC) similar to Group B but with 2 mls autologous MSC in addition to HA. MSC were obtained by bone marrow aspiration, centrifuged, and divided into aliquots, which were cryopreserved. Fifteen animals were equally divided between the groups and sacrificed at 24 weeks after surgery where the joint was harvested and examined macroscopically and histologically. Of the 15 animals, two had died in Group A and one was excluded from Group C due to an infection. In Group A, repair constituted mainly of scar tissue, while in Group B, there was less scar tissue, with small amounts of proteoglycan and collagen II at the osteochondral junction. In contrast, repair cartilage from Group C animals demonstrated almost complete coverage of the defect with evidence of hyaline cartilage regeneration. Histology as assessed by Gill scoring was significantly better in Group C with one-way ANOVA giving an F-statistic of 10.611 with a p-value of 0.004, which was highly significant. Post-operative intra-articular injections of autologous MSC in combination with HA following subchondral drillings into chondral defects resulted in better cartilage repair.
Subchondral drillings for articular cartilage repair give functional improvement that peaks at 24 months after surgery. We postulate that intra-articular injections with autologous peripheral blood stem cells (PBSC) and hyaluronic acid (HA) following subchondral drillings can improve the repair process. Thirty-four patients with full thickness chondral defects of the knee joint underwent subchondral drillings. The operated knees were then placed on continuous passive motion for a period of two hours per day for four weeks, with partial weight-bearing for the first six weeks. PBSC were harvested by apheresis and divided into aliquots which were cryopreserved. One week after surgery, weekly intra-articular injections of 2.5 mLs PBSC mixed with 2 mLs of sodium hyaluronate were given for five weeks after surgery. Patients were followed up for an average of 11 months (range 6–20) and assessed using serial MRI scans. Second look arthroscopy and chondral biopsies were obtained in five patients. International Knee Documentation Committee (IKDC) scores were compared with previous microfractures results from the Mithoefer cohort study using linear interpolation to generate time-based predicted values. The difference was compared using a two-tailed, one-sample T-test against a value of zero. Serial MRI scans showed healing of subchondral bone and evidence of cartilage regeneration that was confirmed on arthroscopy with good integration into surrounding cartilage with no delamination. Biopsy specimens showed attributes typical of hyaline cartilage with good cellular morphology, abundant proteoglycans and Type II collagen. No oedema or degenerative changes were seen. The IKDC data was on average 12.8 points (95% CI 6.5-19.1) higher than the Mithoefer group with p=0.0002. Intra-articular injections of PBSC and HA following subchondral drillings resulted in good repair tissue based on MRI, arthroscopic, and histological criteria, with IKDC scores superior to standard microfracture surgery.
