Postmenopausal osteoporosis (PMOP) is the predominant form of primary osteoporosis. Its etiology remains incompletely elucidated, and the senescence of bone marrow mesenchymal stem cells (BMSCs) is potentially a contributing factor. Kaempferol (Ka), a common flavonoid with antioxidant and anti-inflammatory effects, is a prospective candidate for therapeutic intervention in osteoporosis. However, its impact on BMSC senescence and the underlying mechanisms remains to be elucidated. This study sought to elucidate the impact of Ka on BMSCs and to ascertain its potential targets and regulatory mechanisms. BMSCs were extracted from ovariectomized (OVX) rats to observe the impact of Ka on cellular senescence, mitochondrial function, and mitophagy. Proteomics was utilized to investigate the potential mechanisms. Molecular docking, cellular thermal shift assay, small molecule pull-down assay, and surface plasmon resonance were employed to evaluate the relationship between Ka and its direct target Sp1. Dual-luciferase reporter gene assay and chromatin immunoprecipitation (ChIP) were used to investigate the transcriptional regulatory relationship between Sp1 and FUNDC1. Moreover, we performed detailed imaging and histological observations using micro-CT, hematoxylin and eosin (H&E) staining, Masson staining, immunofluorescence, and immunohistochemistry to assess the role of Ka in rat model of PMOP. Our results indicated that Ka counteracts senescent BMSCs and osteogenic differentiation deficit caused by postmenopausal, which may be achieved by restoring the basal mitophagy level of OVX-BMSCs, mitochondrial function and reducing reactive oxygen species. Furthermore, Ka treatment enhanced bone density and strength, upregulated Sp1 and FUNDC1 expression in the distal femoral region, and the number of γH2AX positive BMSCs decreased. In terms of mechanism, Ka directly binds to Sp1, promoting its transcriptional activation of FUNDC1-mediated mitophagy. Inhibiting mitophagy or Sp1, or FUNDC1 eliminated the therapeutic effect of Ka. Our findings suggest that Ka ameliorates the senescence of OVX-BMSCs by activating the Sp1/FUNDC1 signaling pathway, promoting mitophagy, and providing a new therapeutic strategy and molecular basis for PMOP.

Bone adhesives have gained considerable interest as an adjunctive approach for fragment fixation in comminuted fractures and bone graft procedures. However, the current adhesives are mostly used to fill the bone void to achieve the fixation of broken bones, which inevitably impedes regeneration at the fracture interface. To address this limitation, we present an integrated bone-adhesive bandage that enables robust adhesion to bone tissue without occluding the healing space. Precise modulation of the viscoelastic properties in a poly(octamethylene citrate)–gelatin (POC-G) copolymer facilitates strong interfacial adhesion to bone but also unique internal cohesion to enable self-heal. Further incorporation of hydroxyapatite (HA) nanoparticles significantly enhances the adhesive strength (570.43 ± 21.82 kPa) while preserving mechanical toughness (1648.66 ± 367.81 kJ m⁻³). This strategy further renders POC-G/HA composites with the unique ability to achieve instant, repeatable, and sustained bone fixation in a humid environment, addressing a critical limitation of conventional commercial adhesives. Beyond serving as a superior mechanical fixative, this multifunctional bandage actively orchestrates the bone regeneration process. It promotes the osteogenic differentiation of stem cells, modulates macrophage polarization towards a pro-regenerative M2 phenotype, and stimulates neovascularization to enhance local nutrient and cell supply. This breakthrough design of a pressure-sensitive bone-adhesive bandage opens a new avenue for the instant structural integration of bone fragments and the fixation of bone grafts during surgery. It represents a paradigm shift from passive fixation to active regeneration, potentially revolutionizing therapeutic strategies for bone repair.