Spatiotemporal Release Of SDF-1α And ODN MT01 From Sandwich-like Poly(l-lactide)nanofibrous Membrane For Bone Regeneration

Background: Bone is a powerful supporting organ to maintain the stability of human body shape and movement.However,the clinical treatment of bone tissue injury caused by various reasons is mostly the transplantation of autologous and allogeneic bone,which not only brings a series of related postoperative complications,but also importantly it neglects the natural process of bone healing.Methods: To tackle this problem,inspired by the underlying physiological healing mechanism of bone,we fabricated a bio-functionalized sandwich-like poly(L-lactic acid)(PLLA)nanofibrous membrane scaffold with initial rapid releasing of stromal cell derived factor-1α(SDF-1α)adsorbed on double external layers of nanofibrous membrane to recruit endogenous bone marrow-derived mesenchymal stem cells(BMSCs)and subsequent sustained releasing of oligodeoxynucleotide(ODN)loaded on single middle layer of nanofibrous membrane to induce BMSCs toward osteogenesis for bone regeneration,through physisorption and micro-sol electrospinning technologies.Results: These two biomolecules encapsulated in nanofibrous membrane scaffold were confirmed to be sequentially released as anticipated design via in vitro release experiments.Simultaneously,the developed scaffold exhibited excellent cytocompatibility,which means that cell adhesion and proliferation performance well on the scaffold resembling the extracellular matrix microenvironment.Besides,the scaffold significantly promoted the migration and osteogenic differentiation of BMSCs in vitro by enhancing inherent bone healing physiological processes associated with SDF-1α/CXCR4 signaling and MAPK pathway,respectively.Furthermore,in vivo cranial defect studies verified that the developed scaffold has the superior properties of recruiting BMSCs to the defect sites at the early phrase of bone repair,and markedly accelerated the process of bone healing.Conclusions: Taken together,it was proved to be synergistic and efficacious for nanofibrous membrane scaffold with spatiotemporal and sustained release of SDF-1α and ODN designed according to the physiological process of bone healing to trigger bone regeneration and hopefully provide a broad prospect for clinical applications.