LAUSR

Articular cartilage defects are prevalent and are potentially involved in the initiation of osteoarthritis, yet the lack of efficient therapeutic options to treat cartilage defects represents a substantial challenge. Molecular treatments that require the delivery of therapeutic gene vectors are often less effective that specific, targeted approaches, and the scientific evidence for acellular biomaterial-assisted procedures is limited. Controlled delivery of gene vectors using biocompatible materials is emerging as a novel strategy for the sustained and tuneable release of gene therapies in a spatiotemporally precise manner, thereby reducing intra-articular vector spread and possible loss of the therapeutic gene product. Controlled, biomaterial-guided delivery of gene vectors could be used to enhance intrinsic mechanisms of cartilage repair while affording protection against potentially damaging host immune responses that might counteract the gene therapy component. This Review provides an overview of advances in gene vector-loaded biomaterials for articular cartilage repair. Such systems enable the sustained release of gene therapies while maintaining transduction efficacy. Strategies that harness these properties are likely to result in improved in situ cartilage tissue regeneration that could be safely translated into clinical applications in the near future.Gene therapy and tissue engineering strategies for the treatment of cartilage repair each pose unique challenges to clinical translation. Could combining the two approaches open new avenues for the treatment of articular cartilage defects in patients with osteoarthritis?Key pointsArticular cartilage has a limited capacity for self-repair in terms of strength and sustainability.None of the current pharmacological or surgical options for cartilage repair can completely restore damaged articular cartilage to its original structure and function.Gene therapy holds promise for the treatment of articular cartilage lesions by providing reparative gene sequences at sites of tissue injury.Tissue engineering approaches provide adapted scaffolding matrices that can support the mechanisms of cartilage repair.Host physiological barriers preclude the optimal use of gene therapy or tissue engineering procedures for translational applications to treat articular cartilage injuries.Combining gene therapy and scaffold-mediated approaches might enable the safe, effective and durable regeneration of articular cartilage at lesion sites in patients with osteoarthritis.