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

血管生成 纳米载体 介孔二氧化硅 体内 绒毛尿囊膜 血管内皮生长因子 材料科学 骨形态发生蛋白2 细胞生物学 化学 生物医学工程 药物输送 癌症研究 纳米技术 生物 介孔材料 生物化学 医学 体外 血管内皮生长因子受体 催化作用 生物技术
作者
Ping Sun,Qianqian Zhang,Wei Nie,Xiaojun Zhou,Liang Chen,Haibo Du,Shuguang Yang,Zhengwei You,Jiawen He,Chuanglong He
出处
期刊:ACS Biomaterials Science & Engineering [American Chemical Society]
卷期号:5 (12): 6766-6778 被引量:42
标识
DOI:10.1021/acsbiomaterials.9b01521
摘要

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.
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