Abstract
Introduction: Articular cartilage injuries cause pain and disability and lead to early osteoarthritis. Autologous chondrocytes implantation (ACI) demonstrated long-term clinical benefit. However, clinical application of ACI is laborious requiring arthrotomy of the knee, harvest of a periosteal flap from a secondary surgery site and suturing over the cartilage lesion. Use of the periosteal flap often leads to tissue hypertrophy requiring an arthroscopic intervention. BioCart™II is a new matrix-assisted autologous chondrtocytes implant. The autologous cells, propagated with a unique growth factor variant, are delivered within a biocompatible and biodegradable scaffold made of human fibrin and hyaluronic acid. BioCart™II eliminates the need for a periosteal flap and enables implantation by a minimally invasive procedure thus significantly simplifying surgery and reducing rehabilitation time.
Methods: Chondrocytes were obtained from cartilage tissue using enzymatic digestion. The cells were then expanded in medium supplemented with a fibroblast growth factor (FGF) variant. Chondrogenic potential of the cultured chondrocytes was determined by in vitro high density pellet culture. The pellet cultures were analyzed for expression of cartilage specific markers by PCR and histology. Distribution of the cells within the fibrin-hyaluronic acid scaffold was studied by histology using H& E staining, presence of proteoglycans and collagen types I and II (Col-I, II) was determined by specific stains and immunohistochemistry (IHC).
Results: Cells cultured in the presence of the FGF variant exhibit a dramatic increase in proliferation rate compared with untreated cells. The chondrogenic potential of cells cultured for 4, 7, and 10 days in the presence of the growth factor were tested by pellet culture. Cells cultured for 4 days did not form a hyaline-like pellet, while cells cultured for 7 and 10 days form pellets with hyaline like structure which express proteoglycans and collagen type II. Col-II expression determined by real time PCR was significantly increased compared with Col-I in the pellets indicating the regeneration of hyaline cartilage phenotype. Pellet culture of chondrocytes cultured in the presence of the growth factor formed a much larger pellet and expressed more proteoglycans than pellet of cells cultured without the growth factor. Histological analysis of implants immediately post seeding demonstrate the chondrocytes are distributed throughout the fibrin-hyalronic acid scaffold. Expression of Col-II but not Col-I was observed within the scaffold by IHC.
Discussion: We present a new articular cartilage repair implant composed of autologous cells embedded within a fibrin and hyaluronic acid scaffold. Fibrin which is the natural scaffold for wound healing is used as the implant building material thereby mimicking the body’s natural healing process. The porous open channel structure of the scaffold allows for an immediate three-dimensional distribution of the cells within the scaffold to promote full thickness repair Use of the FGF variant allows implantation of BioCart™II within two to three weeks from the cartilage biopsy and increases the regenerative potential of the implant. BioCart™II is currently in clinical studies for the treatment of knee cartilage injuries.
The abstracts were prepared by Orah Naor, IOA Co-ordinator and Secretary. Correspondence should be addressed to Israel Orthopaedic Association, PO Box 7845, Haifa 31074, Israel.
