Acellular scaffolds, cellular therapy and next generation approaches for knee cartilage repair

Full-thickness knee cartilage defects are a potential source of significant morbidity for patients and incur increased risk for early degenerative joint disease. Recent decades have seen several advancements in the field cartilage repair, among which osteochondral allograft transplantation and autologous chondrocyte implantation stand out as the options with the most durable and efficacious results. There are several limitations, however, to the current generation of cartilage repair options, spanning from cost and availability-related issues to the inherent implications of two-stage surgery, and potentially limited capacity for tissue regeneration. Emerging approaches - the so-called next generation of cartilage repair – are numerous and aim to harness the optimal biological environment and structural support needed to potentially enhance clinical outcomes. The present review offers an overview of next generation approaches for cartilage repair, providing the rationale and available evidence for novel acellular scaffolds, cell-based therapies, mesenchymal stem cells, extra-cellular vesicles (exosomes), allogenic therapies and gene therapy.