Integrated strategies in meniscus tissue engineering: from biomaterials to stem cell-driven regeneration.

Abstract

The meniscus is a fibrocartilaginous tissue essential for load distribution, shock absorption, and knee joint stability, yet its intrinsic healing potential is limited, particularly in the avascular inner zone. Conventional treatments such as partial meniscectomy, repair, or transplantation often fail to restore long-term biomechanical and biological function, underscoring the need for regenerative strategies. Meniscus tissue engineering (TE) has emerged as a promising approach that combines biomaterial scaffolds with stem cells to recreate the structural and functional complexity of the native tissue. This narrative review summarizes recent advances in scaffold design and cell-based therapies for meniscus repair. Natural materials such as collagen, alginate, and silk fibroin provide biocompatibility and bioactivity but lack sufficient mechanical strength, whereas synthetic polymers including PGA, PLA, PLGA, and polyurethane offer tunable degradation and structural reinforcement but are biologically inert. Composite scaffolds that integrate these material classes-through multiphase, gradient, or layered designs-represent a promising strategy to replicate zonal heterogeneity and anisotropic mechanics. On the cellular side, bone marrow-, adipose-, and synovium-derived mesenchymal stem cells have demonstrated potential for zone-specific regeneration, while induced pluripotent stem cells present opportunities for patient-specific therapies but remain limited by safety concerns. Advances in cell seeding strategies, including dynamic perfusion and 3D bioprinting, have further improved scaffold-cell integration. Finally, emerging technologies such as 3D/4D printing, smart responsive biomaterials, controlled drug delivery, dynamic bioreactors, and AI-assisted scaffold design provide new opportunities to overcome persistent challenges of vascularization, mechanical anisotropy, and clinical translation. While significant obstacles remain, the convergence of materials science, stem cell biology, advanced fabrication, and computational modeling offers a promising roadmap toward clinically viable meniscus regeneration.