Hierarchical micro/nanofibrous membranes of sustained releasing VEGF for periosteal regeneration.

The periosteum plays a vital role in both development and injury healing process of bone. However, few researches have focused on artificial periosteum, which was also limited by the complexity on its construction and biological risks for clinical practice. In order to tackle this issue, inspired by the structural development of periosteum, we put forward a hierarchical micro/nanofibrous bionic periosteum with sustained releasing of VEGF as exogenous vascularized fibrous layer of periosteum to induce endogenous cambium layer in vivo for complete regeneration of periosteal and bone tissue, through collagen self-assembly and micro-sol electrospinning technologies. The VEGF encapsulated in hyaluronan-PLLA core-shell structure was demonstrated to be released in a durable way for angiogenesis in fibrous layer and bone defect area. Meanwhile, the self-assembly of collagen together with electrospun fibers contributed to a hierarchical micro/nanostructure which greatly mimicked the microenvironment of extracellular matrix to provide structural and biochemical cues for cell adhesion, proliferation and differentiation, and lead to the formation of cambium layer which mimicked the in-situ ossification manner as intramembranous ossification. As the motif of this study, the periosteal regeneration was characterized both by osteoblasts and periostin, which represented structural and molecular mechanisms respectively. Furthermore, the periosteal biomaterial proposed here possessed the superior abilities of scar inhibition, angiogenesis, osteogenesis to repair the bone defect in a uniform and rapid manner by inherent periosteal ossific mechanism involved in both intramembranous and endochondral ossification. Thus, the endogenous-exogenous combined bionic periosteum proved to be efficient and versatile in triggering periosteal and bone regeneration and hopefully supply a promising strategy for solving clinical issue.