A Bioactive Janus Barrier Membrane Rejuvenates Bone Regeneration in Aging

Aging significantly impairs guided bone regeneration (GBR) by disrupting stem cell recruitment and exacerbating cellular senescence. To address this challenge, we engineered a quercetin and Sr-hydroxyapatite/poly(lactic-co-glycolic acid) (QSHP) Janus barrier membrane. The asymmetric design featured a dense poly(lactic-co-glycolic acid) layer for epithelial exclusion and a functionalized nanowire layer that enabled controlled codelivery of Sr 2+ and quercetin. In vitro, the QSHP membrane markedly enhanced the migration and proliferation of bone marrow mesenchymal stem cells while effectively mitigating H 2 O 2 -induced senescence and restoring osteogenic capacity. In aged rat mandibular defects, the QSHP membrane treatment yielded the highest newly formed bone volume and restored biomechanical properties approaching those of native bone. Histological and immunofluorescence analyses revealed accelerated early osteogenesis, increased recruitment of CD44 + stem cells, and concomitant attenuation of cellular senescence. Collectively, the QSHP membrane rejuvenates the senescence-impaired bone regenerative niche, enabling functional bone regeneration and offering a clinically promising strategy for GBR in aged patients.