Ji Yanhui, Wang Mingbo, Liu Weiqiang, Chen Changsheng, Cui Wei, Sun Tingfang, Feng Qingling, Guo Xiaodong
Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Key Laboratory of Biomedical Materials and Implants, Research Institute of Tsinghua University in Shenzhen, Shenzhen, 518057, China.
J Biomed Mater Res A. 2017 Jun;105(6):1593-1606. doi: 10.1002/jbm.a.35962. Epub 2017 Mar 27.
Both of the osteogenic factor and the suitable delivery system in bone tissue engineering are essential for bone regeneration. In this study, we manufactured two kinds of composite vehicles for sustained release of rhBMP-2 and its derived synthetic oligopeptide (Peptide-24, abbreviated as P24) for osteogenesis and bone defect repair. The composite vehicle was based on cross-linked chitosan, nano-hydroxyapatite/collagen (nHAC), and poly (lactide-co-glycolide) acid microsphere. The physicochemical properties of the composite vehicles (abbreviated as CS/nHAC/PLGA-MS) were investigated. The rhBMP-2 and P24 release kinetics from the vehicles were examined and the secondary structure of rhBMP-2 and P24 after 28 days' release process was analyzed. In vitro cell proliferation, osteogenic differentiation and rat calvarial defect repair were evaluated. The results proved that the composite vehicle had favorable compressive strength, elastic modulus, the porosity, and the bulk density. The secondary structures of rhBMP-2 and P24 kept stability during microencapsulation and release process. P24 from the vehicle kept a geared-up release and rhBMP-2 from the vehicle kept a three-stage mode release process. The results of in vitro cell detection showed that the composite vehicle had good biocompatibility and osteoinduction. In vivo rat calvarial defect repair demonstrated that both groups of vehicles with rhBMP2 and P24 exhibited satisfied bone defect repair. This research showed that the composite vehicle could exhibit sustained release of osteogenic factors. CS/nHAC/PLGA-MS loading rhBMP-2 or P24 could be a novel and ideal scaffold for bone regeneration. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1593-1606, 2017.
骨组织工程中的成骨因子和合适的递送系统对骨再生均至关重要。在本研究中，我们制备了两种用于rhBMP - 2及其衍生合成寡肽（肽 - 24，缩写为P24）持续释放的复合载体，用于成骨和骨缺损修复。复合载体基于交联壳聚糖、纳米羟基磷灰石/胶原蛋白（nHAC）和聚（丙交酯 - 乙交酯）酸微球。研究了复合载体（缩写为CS/nHAC/PLGA - MS）的物理化学性质。检测了载体中rhBMP - 2和P24的释放动力学，并分析了28天释放过程后rhBMP - 2和P24的二级结构。评估了体外细胞增殖、成骨分化和大鼠颅骨缺损修复情况。结果证明复合载体具有良好的抗压强度、弹性模量、孔隙率和堆积密度。rhBMP - 2和P24的二级结构在微囊化和释放过程中保持稳定。载体中的P24保持加速释放，载体中的rhBMP - 2保持三阶段释放模式。体外细胞检测结果表明复合载体具有良好的生物相容性和骨诱导性。体内大鼠颅骨缺损修复表明，含rhBMP2和P24的两组载体均表现出满意的骨缺损修复效果。本研究表明复合载体可实现成骨因子的持续释放。负载rhBMP - 2或P24的CS/nHAC/PLGA - MS可能是一种新型理想的骨再生支架。©2017威利期刊公司。《生物医学材料研究杂志》A部分：105A：1593 - 1606，2017年。
