Biodegradable Mesoporous Silica Nanocarrier Bearing Angiogenic QK Peptide and Dexamethasone for Accelerating Angiogenesis in Bone Regeneration

In the repair of large segmental bone defects, bone tissue is often unable to heal due to the destruction of the vascular network near the wound site. An ideal bone repair material should have both angiogenic and osteogenic capabilities. To achieve this goal, we used biodegradable mesoporous silica nanoparticles (MSNs) as a delivery vehicle for dexamethasone (DEX), a small-molecule drug that induces osteogenic differentiation. Subsequently, chitosan was covalently modified onto the surface of the nanoparticles by glycidoxypropyltrimethoxysilane (GPTMS) to construct nanoparticulate delivery systems (DEX@chi-MSNs) that induce osteoblast formation. The QK peptide, which mimics the α-helical structure of vascular endothelial growth factor (VEGF) binding to the receptor, was adsorbed to the surface of chitosan-modified MSNs nanoparticles (QK@chi-MSNs) to render them with angiogenic ability. The QK@chi-MSNs can promote the formation of the tubular structure of human umbilical vein endothelial cells (HUVECs) and angiogenesis in vivo, as demonstrated by a chicken embryo chorioallantoic test (CAM) and subcutaneous embedding test. The DEX@chi-MSNs can improve alkaline phosphatase (ALP) activity, mineralized nodule formation, and the expression of osteogenic-related genes and proteins by BMSCs. Furthermore, the ability of bone repair and angiogenesis was evaluated in a critical size skull defect model in rats by using nanocarriers loaded with both DEX and QK (QK/DEX@chi-MSNs). The results of computed tomography (CT) scan, histological examination, and immunofluorescence staining indicated that QK/DEX@chi-MSNs can promote bone formation and angiogenesis in vivo, which has broad application prospects in bone tissue engineering.