Winter 2001 Newsletter

The treatment of full thickness defects of articular cartilage remains a problem for orthopaedic surgeons. It has been generally accepted that once articular cartilage is injured and forms a defect, the defect cannot be repaired and bordering intact cartilage changes to degeneration and destroys facing intact cartilage, resulting in osteoarthritis. By promoting migration of mesenchymal stem cells, which is debridement of degenerative tissue from the lesion so that subchondral bone is exposed such as abrasion arthroplasty, subchondral drilling, and microfracture, the reparative tissue changes to fibrocartilage by about six months postoperatively, losing the biomechanical properties of normal articular cartilage.

Other attempts have been developed to repair articular defects by transplanting periosteum, perichondrium, meniscal allograft, autologous osteochondral column graft and prostheses using artificial materials. Each of these techniques to repair the cartilage defect has been only partially successful in that it may reduce pain and increase mobility, but it has gradually deteriorated with time. Although transplantation of periosteum or perichondrium has shown good short-term results, defects transplanted with these materials do not generate hyaline cartilage but rather only fibrocartilage. It often results in bone formation due to endochondral ossification. Autologous osteochondral column grafts can heal defects of hyaline cartilage, but the incongruency of the joint surface between the graft and the host cartilage raises concerns that stress concentration will damage the graft.

In 1994, autologous chondrocytes transplantation used in the clinical reports of Brittberg and colleagues1 raised the expectations of orthopaedic surgeons that a breakthrough in repair of damaged articular cartilage would occur. In their technique, cartilage slices were obtained by arthroscopy from an unloaded area of the femoral condyle; the associated chondrocytes increased in number in a monolayer culture after enzymatic digestion; and the chondrocytes in suspension were then injected into a cartilaginous defect and covered with a flap of the periosteum. According to their report, clinical results were satisfactory and a biopsy of the graft sites showed hyaline-like cartilage repair.

However, we are concerned with their technique in regard to the culture and transplantation procedure. We developed a new technique, which improves upon their technique in terms of 1) maintenance of chondrocyte phenotype during a long cultivation; 2) even distribution of the grafted chondrocytes throughout the osteochondral defects; and 3) low risk of leakage of grafted chondrocytes into the defects. This technique creates new cartilage-like tissue by cultivating autologous chondrocytes embedded in atelocollagen gel for three to four weeks. We carefully selected atelocollagen gel as a three-dimensional culture material from the viewpoint of safety and non-immunogenicity, since atelocollagen gel had been used clinically for the treatment of skin wrinkles in plastic surgery and dermatology. This cultivation results in the proliferation of chondrocytes and the synthesis of an extracellular matrix consisting of chondroitin sulfate and type II collagen at transplantation.2-3 After three to four weeks of cultivation, the atelocollagen gel including chondrocytes had become opaque in color and had acquired a jelly-like hardness (Fig. 1).

Fig. 1: The cartilage-like tissue in which chondrocytes were embedded in atelocollagen gel and cultivated for three weeks.	Fig. 2: Operative procedures. a. Debridement of cartilage defect. b. Fitting a periosteal flap. c. Transplantation of a cartilage-like tissue.

Based on the results of basic studies,2-4 we have applied our technique since 1996 with the approval of the ethics committee of Shimane Medical University. After three to four weeks culture of autologous chondrocytes embedded in atelocollagen gel, a cartilage-like tissue is transplanted into a cartilage defect covered with a periosteal flap, which is sutured with the deep cambium layer facing the subchondral bone plate (Fig. 2). Two weeks after transplantation, continuous passive motion of the joint was initiated. Partial weight-bearing was introduced three weeks postoperatively and was gradually increased to full weight-bearing with muscle training during the first eight weeks after surgery. We treated full-thickness cartilage defects (0.7 to 16.0 cm2) in 50 knees, one elbow and one ankle joint, ranging in age from 13 to 41 years. Clinical, arthroscopic and biomechanical results over a 2-year period indicate that this technique has good potential to treat cartilage defects.5 Although a more prolonged follow-up study should be done to clarify the effectiveness of this procedure, the development of biological technology6-7 will resolve this problematic issue on the inability to repair cartilage within this Bone and Joint Decade (2000-2010).

Fig. 3: Consecutive arthroscopic findings of a 15-year-old boy who had suffered from osteochondral dissecans of the right femoral condyle. a. At initial visit

References:

1. Brittberg M, Lindahl A, Nilsson A, et al. Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation. New Engl J Med. 1994; 331:889-895.
2. Ochi M, Uchio Y, Matsusaki M, Wakitani S. Cartilage repair - A new surgical procedure of cultured chondrocyte transplantation. In: Chan KM, Fu F, Maffuli N, et al, eds. Controversies in Orthopaedic Sport Medicine. Hong-Kong: Williams & Wilkins Asia-Pacific Ltd; 1998:549-563.
3. Uchio Y, Ochi M, J. Matsusaki M, et al. Human chondrocyte proliferation and matrix synthesis cultured in atelocollagen gel. J Biomed Materials Res. 2000; 50:138-143.
4. Katsube K, Ochi M, Uchio Y, et al. Repair of full-thickness articular cartilage defects with allogeneic cultured chondrocytes embedded in atelocollagen gel ­ Comparison with cultured chondrocytes in suspension. Arch Orthop Trauma Surg. 2000; 120:121-127.
5. Ochi M, Uchio Y, Tobita M, Kuriwaka M. Tissue-engineering technique for repair of cartilage defect. Artificial Organs. In Press.
6. Matsusaki M, Ochi M, Uchio Y, et al. Effects of basic fibroblast growth factor on proliferation and phenotype expression of chondrocytes embedded in collagen gel. General Pharmacology. 1998; 31:759-764.
7. Kawasaki K, Ochi M, Uchio Y, et al. Hyaluronic acid enhances proliferation and chondroitin sulfate synthesis in cultured chondrocytes embedded in collagen gels. J Cellular Physiology. 1999; 179:142-148.