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纤维蛋白胶/纤维连接蛋白/肝素基 BMP2 递药系统在 MC3T3-E1 细胞中诱导成骨作用,并在大鼠颅骨临界尺寸缺损中诱导骨形成。

Fibrin Glue/Fibronectin/Heparin-Based Delivery System of BMP2 Induces Osteogenesis in MC3T3-E1 Cells and Bone Formation in Rat Calvarial Critical-Sized Defects.

机构信息

Department of Tissue Engineering, China Medical University, Shenyang 110122, China.

Institute of Regulatory Science for Medical Device, National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, China.

出版信息

ACS Appl Mater Interfaces. 2020 Mar 18;12(11):13400-13410. doi: 10.1021/acsami.0c01371. Epub 2020 Mar 4.

Abstract

Bone morphogenetic proteins (BMPs) have been used to promote bone formation in many clinical scenarios. However, the BMPs are inherently unstable and therefore need to be combined with carriers for controlled delivery. In this study, an innovative and efficient fibrin glue/fibronectin/heparin (FG/Fn/Hep)-based delivery system was developed for controlled release of BMP2. The incorporation of heparin can significantly slow the release of BMP2 without substantially affecting the structure and stiffness of the FG/Fn. The BMP2 release from the FG/Fn/Hep-BMP2 hydrogel is largely dominated by hydrogel degradation rather than simple diffusion. release experiments and MC3T3-E1 cell induction experiments showed that BMP2 can be released steadily and can induce MC3T3-E1 cells to differentiate into osteoblasts efficiently. This process is characterized by the significantly increased expression of calcium deposits, alkaline phosphatase, runt-related transcription factor-2, osteopontin, osteocalcin, and collagen I in comparison with the negative control. assessments revealed that the FG/Fn/Hep-BMP2 hydrogel significantly promotes bone regeneration in a rat calvarial critical-sized defect model. Our investigation indicates that FG/Fn/Hep-BMP2 hydrogel holds promise to be used as an alternative biomaterial for the repair of bone defects.

摘要

骨形态发生蛋白(BMPs)已被广泛应用于多种临床场景以促进骨形成。然而,BMPs 本身很不稳定,因此需要与载体结合以实现控制释放。本研究开发了一种创新且高效的纤维蛋白胶/纤维连接蛋白/肝素(FG/Fn/Hep)基递送系统,用于控制 BMP2 的释放。肝素的掺入可以显著减缓 BMP2 的释放,而不会显著影响 FG/Fn 的结构和硬度。FG/Fn/Hep-BMP2 水凝胶中 BMP2 的释放主要由水凝胶降解控制,而不是简单的扩散。释放实验和 MC3T3-E1 细胞诱导实验表明,BMP2 可以稳定释放,并能有效诱导 MC3T3-E1 细胞分化为成骨细胞。与阴性对照组相比,该过程的特征是钙沉积物、碱性磷酸酶、 runt 相关转录因子 2、骨桥蛋白、骨钙素和 I 型胶原的表达显著增加。评估结果表明,FG/Fn/Hep-BMP2 水凝胶在大鼠颅骨临界尺寸缺损模型中显著促进骨再生。我们的研究表明,FG/Fn/Hep-BMP2 水凝胶有望成为修复骨缺损的替代生物材料。

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