CaReS®, cartilage regeneration system: Autologous chondrocyte transplantation in a collagen gel

Abstract

Articular cartilage is a white, shiny, moisture tissue comprising less than 5 % cells, about 35 % extracellular matrix of mostly collagen type II and proteoglycans and about 60 % water, and provides outstanding biomechanics. Hence the tissue looks simple in its structure; the biomechanical properties are linked to the complex nanostructured architecture of the tissue, which partly relates to the high water content bound to macromolecules [26]. Since the composition of articular cartilage is not restored by natural healing, many attempts have been made to improve the quality of the repair tissue including microfracture [13] or osteochondral autografting; both methods are limited due to tissue quality or resources of grafts [3, 8, 10, 16]. Autologous chondrocyte transplantation has changed the paradigm of the treatment of cartilage defects from repair to regeneration, and this has been demonstrated in randomised trials proving the concept of regenerating tissue in a cell-based therapy approach [21]. However, the limitations of the periosteal flap concerning size and thickness and surgical demands with suturing and the variability of biological reaction including hypertrophy, calcification and delamination [2, 16, 17, 20, 27], as well as the uncontrolled cell transplantation in a cell suspension [25], have supported the introduction of the use biomaterials as a scaffold. The first attempt was to replace the periosteal flap by a collagen membrane which were sutured or glued to the defect combined with the cell suspension injected or seeded onto the membrane during the surgery before implantation [2, 4, 9, 15, 19]. Concerns about the phenotype of the cultured cells led to preculturing techniques on biomaterials in sponges or gels to maintain the chondrocytic function of the cells and allow a more controlled dispersion of the chondrocytes throughout the defect [22]. The matrix characteristics concerning biochemical composition, biophysical appearance in gel, foams or sponges, degradation dynamics and products, toxicity, immunological reactions and general biocompatibility are important parameters of biomaterial development [1, 5, 9, 15, 18]. The cell-biomaterial interaction in a biological environment is the decisive process of successful cartilage regeneration.