Microenvironment-bionic scaffold and multi-cell spatial patterning for area-specific meniscus regeneration.

Abstract

The limited regenerative capacity of injured meniscal tissue necessitates the development of advanced tissue-engineered alternatives. However, conventional homogeneous meniscal implants often fail to replicate the inherent area-specific architecture of the native meniscus. Herein, we present a synergistic regeneration strategy to fabricate a Biomimetic Area-specific Meniscus (BAM), integrating biomimetic microenvironmental modulation with spatially organized multicellular patterning. This study engineered a composite scaffold by combining meniscus-derived decellularized extracellular matrix (Me-dECM) with a 3D-printed polycaprolactone (PCL) framework, which demonstrated favorable bioactivity and mechanical robustness. Through a post-occupancy sacrifice (POS) strategy employing thermosensitive Pluronic F-127 hydrogel, this study achieved precise spatial arrangement of fibrochondrocytes (FCs) and fibroblasts (FBs), resulting in a continuously tripartite meniscal construct with heterogeneous spatial organization. In vitro and in vivo assessments confirmed that this tripartite design effectively recapitulates native meniscal regional heterogeneity, exhibiting gradient distributions of collagen types I and II (COL I/II) and sulfated glycosaminoglycans (GAGs), thereby accomplishing structural and functional biomimicry. Collectively, the BAM strategy enables the regeneration of a mechanically competent, gradient-heterogeneous meniscus, offering a promising translational pathway for functional meniscal reconstruction.