Cellular senescence of bone marrow mesenchymal stem cells (BMSCs) represents the fundamental pathological barrier to healing in osteoporotic patients. This study reports a multifunctional bone scaffold specifically designed to reverse this senescent phenotype by upregulating Slc25a33 and Crabp1, key regulators of mitochondrial biogenesis and retinoic acid signaling. The scaffold features interconnected spindle-shaped pores (long axis ∼100 μm) inspired by trabecular bone canalicular lacunae, combining polylactic acid nano-oriented fibers and Type I collagen to simulate rod-like and plate-like trabeculae. This biomimetic design enhances mechanical performance (Young's modulus: 51.478 ± 0.993 MPa, porosity: 65.341 ± 0.863%), facilitates cell migration and substance exchange, and continuously provides Type I collagen to the microenvironment. In vitro scaffold extracts reversed senescence in aged BMSCs, enhancing proliferation (wound closure: 42.46 ± 8.47% vs 39.51 ± 4.35%, p p < 0.05) with activated oxidative phosphorylation and osteogenic pathways. This biomimetic scaffold reverses BMSC senescence to restore bone regeneration capacity in osteoporotic defects.
Jiang et al. (Tue,) studied this question.