BRISTOL, UK—Anthony Hollander, PhD, and colleagues in Britain and in Italy have been working for several years on a method for patching damaged knees. Dr. Hollander, who is Professor of Rheumatology and Tissue Engineering at Bristol University, UK, reports in the July issue of Tissue Engineering that the custom-made patches induce cartilage regeneration as soon as 11 months after implantation and that they work even better in knees with early osteoarthritis (OA) than in those that were normal prior to injury.¹

"My best guess is that the early stages of OA represent an attempt at repair to damaged cartilage. This is usually destined to fail, but by adding freshly grown cells into this repair environment we are tipping the balance in favor of successful regeneration. As a note of caution," Dr. Hollander told CIAOMed, "later-stage OA may be quite different."

The investigators point out that articular cartilage has a slow turnover rate, is avascular, and heals slowly if at all.  That makes it a prime target for some form of tissue patch in the hope of heading off the downward spiral from cartilage injury to OA and the need for total joint replacement.

True regeneration requires that the implanted patch mature and acquire the key functional characteristics of the normal tissue. Dr. Hollander's group report that their patch develops many of the hallmarks of native cartilage. The patch is constructed of erythrocytes isolated from bits of healthy cartilage removed from the damaged knee by arthroscope, cultured, seeded onto HyalograftR C esterified hyaluronic acid scaffolds (Fidia Advanced Biopolymers, Abano Terme, Italy), and grown for 14 days before implantation.

These include erythrocytes organized into columns aligned perpendicular to the articular surface, type II collagen bundles organized parallel to the surface in the most superficial tissue, collagen fibrils organized into hyaline— more type II collagen and little type I collagen—production of an intact smooth surface by integration with surrounding cartilage, integration of deep-zone cartilage with subchondral bone (with production of a "tidemark" calcified cartilage layer at the interface), and biochemical maturation to normal or nearly normal levels of specific collagens and proteoglycans.

In this study, 23 patients (mean age 35.6 years) with chondral defects of the knee received implants, which were examined by second-look arthroscope and full-depth, 2-mm diameter biopsy an average of 16 months later (range 6-30 months). The mean surface area implanted was 5.0 cm². These biopsies were compared with similar biopsies from the otherwise normal knees of seven patients undergoing above-knee amputation for bone tumors. The macroscopic appearance of the cartilage was assessed by International Cartilage Repair Society (ICRS) criteria, which include degree of defect repair, integration to border zone, and macroscopic appearance.  The subjects had single (48%) or multiple (52%) chondral defects caused by trauma or osteochondritis dissecans. Most lesions (83%) were on the femoral condyles. Nine of 23 patients had already developed OA.

The investigators report that implants in 10 of the 23 subjects achieved the appearance of normal cartilage, 10 had abnormal cell organization, and 3 had mixed fibrocartilage and normal tissue. All of the biopsies with normal cellular distribution had "the typical hyaline organization of collagen fibrils...[suggesting] that organization of cells into clusters or columns is associated with a mature organization of the extracellular matrix," the authors wrote.

The possibility that OA might impede the implantation and/or maturation of engineered cartilage tissue implants has been a concern for researchers; thus, Dr. Hollander and colleagues were pleasantly surprised to find that this was not the case. They report, "The repair tissue was mature hyaline cartilage in 36% of biopsies taken from nonarthritic joints and 67% of biopsies from the osteoarthritic knees. Furthermore, 3 patients had advanced osteoarthritis (Ahlback score of IV on the V-point scale), and in 2 of these cases, the cartilage repair tissue was clearly hyaline."

They conclude that, "taken together, these observations suggest that a better quality of hyaline cartilage repair tissue—more type II collagen and proteoglycan, less type I collagen—can be generated in osteoarthritic knees than in those without osteoarthritis."

"Pre-existing OA was the only clinical parameter showing any association with outcome. However, this was a small study," Dr. Hollander warned.

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