Major biological obstacles for persistent cell-based regeneration of articular cartilage

Abstract

Hyaline articular cartilage, the load-bearing tissue of the joint, has very limited repair and regeneration capacities. The lack of efficient treatment modalities for large chondral defects has motivated attempts to engineer cartilage constructs in vitro by combining cells, scaffold materials and environmental factors, including growth factors, signaling molecules, and physical influences. Despite promising experimental approaches, however, none of the current cartilage repair strategies has generated long lasting hyaline cartilage replacement tissue that meets the functional demands placed upon this tissue in vivo. The reasons for this are diverse and can ultimately result in matrix degradation, differentiation or integration insufficiencies, or loss of the transplanted cells and tissues. This article aims to systematically review the different causes that lead to these impairments, including the lack of appropriate differentiation factors, hypertrophy, senescence, apoptosis, necrosis, inflammation, and mechanical stress. The current conceptual basis of the major biological obstacles for persistent cell-based regeneration of articular cartilage is discussed, as well as future trends to overcome these limitations.

Figure 1

Biological obstacles associated with cell-based approaches to cartilage tissue engineering. Formation of hyaline neocartilage can be hindered due to loss of transplanted chondrogenic cells by cellular efflux, apoptosis or necrosis, differentiation insufficiencies, including fibroblastic, hypertrophic or osteogenic differentiation (red arrows), matrix destruction by mechanical, oxidative and/or inflammatory stressors (red flashes), as well as integration failures within the cartilage and/or bone compartment (green arrows) of the defect.