Tissue engineering for articular cartilage repair – the state of the art

Abstract

Adult articular cartilage exhibits little capacity for intrinsic repair, and thus even minor injuries or lesions may lead to progressive damage and osteoarthritic joint degeneration, resulting in significant pain and disability. While there have been numerous attempts to develop tissue-engineered grafts or patches to repair focal chondral and osteochondral defects, there remain significant challenges in the clinical application of cell-based therapies for cartilage repair. This paper reviews the current state of cartilage tissue engineering with respect to different cell sources and their potential genetic modification, biomaterial scaffolds and growth factors, as well as preclinical testing in various animal models. This is not intended as a systematic review, rather an opinion of where the field is moving in light of current literature. While significant advances have been made in recent years, the complexity of this problem suggests that a multidisciplinary approach -combining a clinical perspective with expertise in cell biology, biomechanics, biomaterials science and high-throughput analysis will likely be necessary to address the challenge of developing functional cartilage replacements. With this approach we are more likely to realise the clinical goal of treating both focal defects and even large-scale osteoarthritic degenerative changes in the joint.

New perspectives for articular cartilage repair treatment through tissue engineering: A contemporary review

“…The inherent ability of MSCs to self-renew opens the possibility that cell expansion may be achievable post-implantation [25] . The differentiation of MSCs into different cell types, in this case to produce cartilage tissue, is reliant on the local microenvironment, and growth factors, extracellular matrix and mechanical forces [25,26] .…”

“…The differentiation of MSCs into different cell types, in this case to produce cartilage tissue, is reliant on the local microenvironment, and growth factors, extracellular matrix and mechanical forces [25,26] . MSCs are easily available from bone marrow, synovial membrane, solutions do not perfectly restore cartilage, some of the latest technologies start to bring very promising results in repairing cartilage from traumatic injury or chondropathies.…”

“…On the contrary, MSCs are very stable and they do not suffer this dedifferentiation process and have a high differentiation capacity [35] . Beside the characteristics of MSCs expounded above, these cells have self-renewal potential as well as multilineage differentiation potential [36,37] , including chondrogenesis [25] . A defined medium for in vitro chondrogenesis of MSCs was first reported by Johnstone et al [25] in 1998, who used micromass culture with TGF-β and dexamethasone.…”

“…Beside the characteristics of MSCs expounded above, these cells have self-renewal potential as well as multilineage differentiation potential [36,37] , including chondrogenesis [25] . A defined medium for in vitro chondrogenesis of MSCs was first reported by Johnstone et al [25] in 1998, who used micromass culture with TGF-β and dexamethasone. To date, the micromass culture is widely used to evaluate chondrogenic potential of MSCs "in vitro".…”

“…However, this "in vitro" chondrogenesis does not imitate cartilage formation during development. During micromass culture, MSCs increase expressions of both collagen type Ⅱ (chondrocytes marker) and Ⅹ (hypertrophic chondrocytes marker) [25] . Other cytokines such as insulin like growth factor (IGF), bone morphogenetic protein (BMPs) and parathyroid hormone related peptide (PTHrP) had been tried for better differentiation of the cells, but it is still difficult to obtain "in vitro" MSCbased cartilage formation comparative to native cartilage tissue [25] .…”