Replicating the post-chemotherapy tumor microenvironment via biomimetic scaffolds to regulate MSC differentiation

The repair of tumor-induced bone defects requires regenerative materials capable of functioning within the harsh conditions of cancer therapy. Herein, we introduce a biomimetic scaffold designed to simulate the post-chemotherapy tumor microenvironment to investigate its specific effects on tissue regeneration. The scaffold features a PLGA knitted mesh/collagen sponge hybrid loaded with mineralized, DOX-carrying mesoporous silica nanoparticles (DOX-MSNCaP). The sustained release of DOX facilitates potent tumor cell elimination, thereby establishing a residual post-chemotherapy microenvironment. We subsequently explored the biological response of mesenchymal stem cells (MSCs) to this specific biomimetic environment. Our results indicate that the scaffold significantly enhances MSC adhesion and drives osteogenic differentiation through the upregulation of YAP/TAZ signaling. Overall, these findings suggest that following tumor eradication, the scaffold effectively facilitates MSC-mediated osteogenesis, serving as a promising therapeutic strategy for post-tumor bone reconstruction.