Reverse biogradient biomimetic periosteum with osteogenic and angiogenic characteristics for bone regeneration

The periosteum is critical for bone reconstruction. Despite serving as a clinical "induced periosteum" treatment for bone defects, the induced membrane technique is associated with significant psychological distress and economic burden due to the need for secondary surgery. Inspired by the ability of induced membranes to function like the periosteum, we propose a tissue-engineered periosteum to replace induced membranes for bone regeneration. This study confirmed that the induced membrane and periosteum share similar architectural and biological properties, including a loose inner layer, a dense outer layer, and a protein expression pattern. An asymmetric nanofibrous membrane was fabricated by electrospinning using gelatin and chitosan, with bone morphogenetic protein (BMP-2) and functionalized hydroxyapatite (Func-HA) incorporated to construct a biomimetic periosteum featuring a reverse biogradient for bone reconstruction and regeneration. The reverse biogradient biomimetic periosteum could significantly enhance osteogenesis and angiogenesis. Interestingly, the biomimetic periosteum also provided a periosteum-mimetic microenvironment by enhancing periosteal stem cells (PSCs) recruitment to the bone defect region and upregulating periostin expression. Our findings suggest that biomimetic membranes with a reverse biogradient could be promising alternatives to induced membranes.