Growth factor collected cell membrane-functionalized matrix for vascular-innervated bone regeneration

Abstract

Peripheral nerves and blood vessels regulate the development process of bone tissue by delivering neural and vascular-related cytokines. However, challenge of preventing the loss of neural and vascular growth factors and ensuring their long-term availability for bone defects was often been overlooked. The current study designed a hybrid cell membrane with specific surface receptors for calcitonin receptor (CTR) and vascular endothelial growth factor receptor (VEGFR) through overexpressed the CTR receptor gene (Calcr) and the VEGFR 1 gene (Flt-1). The bone repair matrix functionalized by the hybrid cell membrane (GCMs) had collecting property for neurogenic growth factor (NGF) and vascular endothelial growth factor (VEGF). Furthermore, GCMs enhanced neural and vascular differentiation in mesenchymal stem cells (MSCs) and stimulated osteogenic differentiation of MSCs through neural and vascular-related paracrine signals. GCMs also facilitated the angiogenesis and neurogenesis around bone defects, further promoted the repair of rat skull defects. This study suggests a promising approach for using cell membranes to harvest growth factors for innervation and vascularization in bone reconstruction.