Articular Cartilage Defects—Plug it or Cell it?
Abstract & Commentary
Synopsis: A randomized, prospective study found equivalent clinical outcomes for articular cartilage defects treated with either osteochondral plug grafts or autologous chondrocyte implantation (ACI). ACI improvement took longer, and the histology revealed mainly fibrocartilage, calling into question any advantage to this technique.
Source: Horas U, et al. Autologous chondrocyte implantation and osteochondral cylinder transplantation in cartilage repair of the knee joint. J Bone Joint Surg Am. 2003;85-A(2): 185-192.
It is well established that articular cartilage defects lack the intrinsic ability to heal. What is less established is the ideal treatment for larger, symptomatic lesions. Horas and colleagues of this study from Germany prospectively randomized 20 patients each to treatment with either osteochondral plug autografts (also called OATS or mosaicplasty) or autologous chondrocyte implantation.
Each patient had a single, symptomatic, moderate-sized lesion (average about 3.7 cm2) involving the weight-bearing region of the femoral condyle. ACI involved a cartilage biopsy procedure followed 3 weeks later by open implantation of the culture-expanded cells beneath a periosteal patch, cambium layer down. The osteochondral plug group had grafts taken from the superior-medial trochlear ridge first and posterior condyles second, depending on how many were needed, and implanted simultaneously via an open approach. Both groups underwent an identical, conservative rehab course that gradually progressed weight bearing and activity over 12 weeks. Patients were evaluated at 6, 12, and 24 months following surgery, with arthroscopy and biopsies obtained in about one-quarter of patients in each group. Immunohistochemical staining was performed for collagens type I, II, III, VI, and X, and aggrecan and protein S-100.
No clinical differences were discernable between groups by Tegner activity scores or Meyers score at 2 years. Using Lysholm knee scores, the ACI group took longer to improve with slightly lower scores at all time points. More importantly, the light microscopy, scanning electron microscopy, and immunohistochemistry results all demonstrated the repair tissue for ACI was almost entirely fibrocartilage, with rare areas that were hyaline-like upon review by blinded pathologists. Another concern on EM was that the ACI regenerate tissue had many missing cells, raising the possibility of early cell death of the transplanted chondrocytes. On the contrary, the autologous plugs were both microscopically and biochemically identical to surrounding normal cartilage, with the only possible problem being persistent clefts separating the plug from adjacent intact cartilage. Horas et al recommend waiting for longer-term results before performing ACI on larger numbers of patients.
Comment by David R. Diduch, MS, MD
This represents the first paper that is both randomized and prospective regarding these 2 commonly used treatments for cartilage lesions. More importantly, it also is the first paper to report ACI results by investigators not directly linked to ACI commercially, and for these reasons, this is a most welcome addition to the literature. Their results for ACI are concerning for several reasons, including the regenerate tissue being basically fibrocartilage, having almost no biochemical or histological makeup of hyaline cartilage, and being devoid of cells in many areas. They conclude with a warning to hold the procedure before using it on large numbers of patients.
The osteochondral plug results, on the other hand, were quite encouraging. The transplanted cartilage had no discernable differences from the surrounding native cartilage even at 2 years. The clefts around the plugs probably do not matter clinically as they were quite small and showed no signs of progressing in size. Perhaps performing an abrasion chondroplasty at the time of transplantation would encourage fibrocartilage to fill these spaces better between plugs. The details of number of plugs and location of harvest are somewhat sketchy, but Horas et al’s general approach is fewer plugs of larger diameter.
That the osteochondral plugs were able to treat the same size defects as the ACI technique—with much better histology, a quicker recovery, 1 fewer operation, and a dramatic fraction of the cost—should bolster the use of plug transfer as an established technique. The creation of the Tracking or "T" codes has given the insurance industry unwarranted license to treat this procedure as "experimental." Papers like this will help to justify its use. On the contrary, papers like this call into question the value of ACI and further question in my mind whether the expensive transplanted cells do anything of substance as compared to the periosteal patch.
Dr. Diduch is Associate Professor, Department of Orthopaedic Surgery, University of Virginia School of Medicine, Charlottesville, VA