The role of costal cartilage in musculoskeletal regeneration: A systematic review.

Purpose: Musculoskeletal tissue regeneration remains a major clinical challenge due to the limited intrinsic healing capacity of cartilage, bone and interface tissues, as well as the complexity of recreating their hierarchical structure and mechanical properties. In recent years, costal cartilage (CC) has emerged as a promising and versatile resource for regenerative applications, owing to its hyaline cartilage composition, biological plasticity and relative surgical accessibility. This systematic review aims to critically evaluate in vivo and clinical evidence published over the last decade regarding the use of CC-derived cells and matrices for musculoskeletal tissue regeneration. Methods: A systematic search of PubMed, Scopus and Web of Science databases was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, identifying 26 eligible studies, including 18 in vivo and 8 clinical investigations. Results: CC was employed either as a source of costal chondrocytes or cartilage-derived stem cells, or as decellularized or particulate extracellular matrix scaffolds. Preclinical studies demonstrated consistent regenerative potential across cartilage, osteochondral, bone and enthesis models, with outcomes showing hyaline-like tissue formation, improved biomechanical properties, enhanced integration with host tissue and coordinated chondrogenic and osteogenic responses. Clinical studies, primarily focused on cartilage and osteochondral defects, reported significant improvements in patient-reported outcomes, imaging-based repair quality and functional recovery, with follow-up periods extending up to 5 years and a favourable safety profile. Conclusions: Cell-based CC approaches showed robust biological efficacy but were associated with greater regulatory and translational complexity due to substantial manipulation requirements. In contrast, matrix-based CC strategies offered a more readily translatable option, leveraging the intrinsic bioactivity of the extracellular matrix while reducing regulatory burden. CC could be considered a highly promising and adaptable platform for musculoskeletal regeneration. However, heterogeneity in study design, limited sample sizes and variable methodological quality highlight the need for standardized protocols and well-designed, long-term randomized clinical trials to definitively establish clinical indications and optimize therapeutic strategies. Level of Evidence: N/A.