Zonally patterned demineralized bone matrix–meniscus ECM composite scaffold directing region-specific fibrochondrogenic and angiogenic responses

Abstract

The human meniscus is a zonal fibrocartilage characterized by inner-outer gradients in matrix composition and outer vascularity, essential for mechanical function and tissue integration. However, these hierarchical features are rarely reproduced in current meniscal substitutes, limiting durability and biological integration after repair. Here, we developed a triphasic scaffold composed of a demineralized bone matrix (DBM) framework integrated with regional decellularized meniscus extracellular matrix (DMECM) using riboflavin-mediated photo-crosslinking. This strategy enabled spatial localization of zonal DMECM compartments within a robust scaffold. The zonally patterned DBM + DMECM scaffold preserved interconnected porosity and mechanical stability, supported mesenchymal stem cell (MSC) adhesion and guided region-dependent fibrochondrogenic differentiation in vitro. Subcutaneous implantation of MSC-seeded scaffolds resulted in organized ECM remodeling and a graded angiogenic response across the inner, middle and outer regions. In vitro endothelial assays confirmed that these vascular patterns arise from intrinsic zone-specific DMECM cues, recapitulating the native avascular-to-vascular hierarchy. Together, these findings demonstrate that the triphasic DBM + DMECM scaffold restores biochemical and angiogenic gradients of the native meniscus, enabling coordinated fibrochondrogenic and vascular responses. The use of clinically established materials supports the translational potential of this platform for post-meniscectomy defect reconstruction and fibrocartilaginous interface engineering.