A Coordinated Cascade Therapy‐Based Janus Fibrous Membrane Drives Bone Regeneration through Mediating the Transformation of Energy Metabolism Pathway

Abstract Bone regeneration is synergistically regulated by growth factors, which are expressed in a coordinated cascade of events. An ideal guided bone regeneration membrane (GBRM) shall present barrier and antibacterial functions, and promote osteogenesis through time‐controlled release of growth factors. In this study, a coordinated cascade therapy‐based Janus fibrous membrane is fabricated by coaxial electrospinning and layer‐by‐layer self‐assembly technology (LBL). Specifically, the oriented PCL/PLGA fibers loaded with zinc oxide nanoparticles (ZnO NPs) are designed as the outer layer, and randomly arranged core‐shell Gelatin/PLLA nanofibers are employed as the inner layer to rapidly release aFGF and sustainedly release BMP‐2. Results demonstrated that the Janus fibrous membrane achieved multiple functions to satisfy essential requirement of bone regeneration, which exhibited remarkable antibacterial ability, barrier function, osteoinductive ability. Interestingly, the significant enhancement of oxidative phosphorylation (OXPHOS) as the major energy supply pathway is the decisive factor to drive osteogenic differentiation of BMSCs induced by Janus fibrous membranes. This study provides a novel strategy to fabricate multifunctional membranes/scaffolds, displaying great potential applications in tissue engineering. Besides, understanding the synergistic mechanism of time‐controlled release of growth factors on the cellular energy metabolism process can provide deeper insights into growth factors‐mediated tissue regeneration and optimizing healing outcomes.