ECM-Derived Electrospun and Electrospun-Hybrid Scaffolds for Cartilage Regeneration: From Matrix Mimicry to Clinical Translation.

Cartilage regeneration remains a major clinical challenge due to the tissue's limited intrinsic healing capacity and the shortcomings of current interventions, which frequently result in fibrocartilage formation rather than restoration of native hyaline cartilage. Extracellular matrix (ECM)-derived electrospun scaffolds have emerged as a promising biomimetic strategy by integrating ECM-relevant biochemical motifs with a fibrous architecture that can be engineered to approximate aspects of cartilage ECM organization. These scaffolds, fabricated from natural ECM components such as collagen, gelatin, hyaluronic acid (HA), chitosan (CS), silk fibroin (SF), alginate, and chondroitin sulfate (ChS), are frequently selected to enhance bioactivity and cell-matrix interactions. This review summarizes ECM-derived electrospun scaffolds for cartilage regeneration, with emphasis on material selection, fabrication strategies, bioactive functionalization, and preclinical performance. We highlight the transition from single-component natural polymer scaffolds to complex hybrid constructs that integrate multiple ECM components including fiber-hydrogel composites and multilayer/aligned fiber designs aimed at recapitulating depth-dependent features of cartilage. Further developments include the incorporation of decellularized cartilage matrix as a tissue-specific ECM source. Although preclinical studies consistently report enhanced chondrogenesis and cartilage-like tissue formation, significant challenges persist, particularly with respect to optimizing mechanical performance, regulating degradation kinetics, and scaling manufacturing processes. Accordingly, we discuss key translation-limiting factors─mechanical robustness under joint loading, reproducible ECM sourcing and characterization, and regulatory/manufacturing considerations─and outline design priorities to bridge promising preclinical outcomes with clinical feasibility.