Modern athletes are constantly susceptible to performance-threatening injury as they push their bodies to greater limits and endure higher physical stresses. Loss of performance and training time can adversely and permanently affect a sportsperson’s career. Now more than ever with advancing medical technology the answer may lie in biologic therapy. We have been using peripheral blood stem cells (PBSC) clinically and have been able to demonstrate that stem cells differentiate into target cells to enable regenerative repair. The potential of this technique as a regenerative agent can be seen in three broad applications: 1) articular cartilage, 2) bone and 3) soft tissue. This article highlights the successful cases, among many, in all three of these applications.

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.

Purpose: A pilot study to assess whether intra-articular injections of autologous marrow-derived stem cells (MSC) and hyaluronic acid (HA) will result in a better quality of cartilage regeneration after subchondral drillings into surgically created full-thickness chondral defects.

Methods: 15 male goats were subjected to full-thickness chondral defects followed by subchondral drillings. The goats were divided into three groups: Group A, no injection (control group); Group B, a weekly intra-articular injection of HA for three consecutive weeks; Group C, a weekly intra-articular injection of autologous MSC in combination with HA for up to three consecutive weeks. The intra-articular injections were given one week after surgery. Group C goats underwent bilateral iliac crest bone marrow aspiration during surgery. The bone marrow aspirates were centrifuged and bone marrow cell suspension were then divided into vials and cryo-preserved. Prior to usage, the bone marrow cells were thawed and prepared for intra-articular injections. The repaired chondral defects were visually inspected and histologically examined at week 24.

Results: In groups A and B goats, the defects showed repair with mainly fibrous tissues. Chondral defects in Group C goats showed better repair of tissues with some specimens showing mainly hyaline cartilage as compared to the other groups.

Conclusion: Intra-articular injections of autologous MSC in combination with HA following subchondral drillings into chondral defects result in a better quality of neochondrogenesis. Preliminary results from on-going human clinical trials provide similar evidence of articular cartilage regeneration following subchondral drillings into chondral defects followed by post-operative intra-articular injections of autologous peripheral blood stem cells (PBSCs) in combination with HA.

Purpose: To assess the results of chondrogenesis in the knee joint following subchondral drillings into chondral defects followed by post-operative intra-articular injections of autologous peripheral blood stem cells (PBSCs) in combination with hyaluronic acid (HA).

Methods: 10 patients with full thickness chondral defects treated with arthroscopic multiple subchondral drillings from an on-going clinical trial were included, with a minimum follow up of two years. Post-operatively, the operated knee was placed on continuous passive motion two hourly per day for a period of 4 weeks and was on partial weight bearing for the first six weeks. Autologous PBSCs were harvested by the process of apheresis after surgery. The harvested PBSCs were then divided into vials and cryo-preserved for later use. One week after surgery, a five weekly intra-articular injections of PBSCs (2.5mls) mixed with HA (2mls) were commenced.

Results: Sequential MRI scans showed healing of the subchondral bone with evidence of chondrogenesis. Second look arthroscopy with biopsy on four patients confirmed chondrogenesis and satisfactory incorporation of the newly regenerated cartilage with the surrounding articular cartilage. Chondral biopsy showed full thickness mature chondrocytes with the presence of hyaline cartilage. All patients showed improved IKDC scores post-operatively. Apart from the discomfort of PBSCs harvesting and localized pain associated with the intra-articular injections, there were no other notable adverse reactions.

Conclusion: This is a simple and effective method of regenerating articular cartilage involving only a single arthroscopic procedure followed by post-operative out-patient intra-articular injections of autologous PBSCs combined with HA.