Biomimetic Bamboo-Inspired Bone Repair Scaffold: Reversing Degraded States and Promoting Mesenchymal Stem Cell Differentiation

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%, <i>p</i> < 0.05), migration, and osteogenic differentiation through Slc25a33/Crabp1 upregulation. In vivo 15-month-old osteoporotic rats showed superior bone regeneration at 12 weeks versus allogeneic bone controls, with significantly improved cancellous bone parameters (BV/TV, Tb.N, and Tb.Th). Single-cell sequencing confirmed expansion of a rejuvenated BMSC subpopulation (cluster 2: 27.9% vs 0.0%, <i>p</i> < 0.05) with activated oxidative phosphorylation and osteogenic pathways. This biomimetic scaffold reverses BMSC senescence to restore bone regeneration capacity in osteoporotic defects.