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

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 < 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%, p < 0.05) with activated oxidative phosphorylation and osteogenic pathways. This biomimetic scaffold reverses BMSC senescence to restore bone regeneration capacity in osteoporotic defects.