Dual siRNA‐Loaded Cell Membrane Functionalized Matrix Facilitates Bone Regeneration with Angiogenesis and Neurogenesis

Abstract Vascularization and innervation play irreplaceable roles in bone regeneration and bone defect repair. However, the reconstruction of blood vessels and neural networks is often neglected in material design. This study aims to design a genetically functionalized matrix (GFM) and enable it to regulate angiogenesis and neurogenesis to accelerate the process of bone defect repair. The dual small interfering RNA (siRNA)‐polyvinylimide (PEI) (siRP) complexes that locally knocked down soluble vascular endothelial growth factor receptor 1 (sFlt‐1) and p75 neurotrophic factor receptor (p75 NTR ) are prepared. The hybrid cell membrane (MM) loaded siRP is synthesized as siRNA@MMs to coat on polylactone (PCL) electrospun fibers for mimicking the natural bone matrix. The results indicates that siRNA@MMs could regulate the expression of vascular‐related and neuro‐related cytokines secreted by mesenchymal stem cells (MSCs). GFMs promote the expression of osteogenic differentiation through paracrine function in vitro. GFMs attenuates inflammation and promotes osseointegration by regulating the coupling of vascularization and innervation in vivo. This study uses the natural hybrid cell membrane to carry genetic material and assist in the vascularization and innervation function of two siRNA. The results present the significance of neuro‐vascularized organoid bone and may provide a promising choice for the design of bone tissue engineering scaffold.