Yang Liang, Huang Jinghuan, Yang Shuyi, Cui Wei, Wang Jianping, Zhang Yinping, Li Jingfeng, Guo Xiaodong
Department of Orthopedics, Zhongnan Hospital of Wuhan University, 169 Donghu Road, Wuhan 430071, People's Republic of China.
Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, People's Republic of China.
ACS Biomater Sci Eng. 2018 Sep 10;4(9):3246-3258. doi: 10.1021/acsbiomaterials.7b00780. Epub 2018 Aug 9.
A novel PTH-derived peptide, PTHdP, including a repetitive aspartic acid sequence at the C-terminal and phosphorylated serine at the N-terminal has been previously designed. To evaluate its potential as a bone growth factor for bone tissue engineering, true bone ceramics incorporated with nanohydroxyapatite coating and chitosan (CH/TBC) was developed as a desired three-dimensional porous delivery carrier in this study. In vitro results showed that PTHdP could be loaded with high-efficiency and subsequently released in a controlled and sustained manner from CH/TBC. Bioactivity of released PTHdP was retained and able to exert a significant effect on promoting or inhibiting osteogenesis actions when exposed intermittently or continuously, respectively, for MC3T3-E1 cell culture. As evaluated in a critical-size rabbit radial defect model by radiographic and histological examination, the combination of CH/TBC scaffolds with PTHdP exhibited a remarkably stronger capacity to stimulate new bone formation than control and pure CH/TBC groups. These results indicated the novel PTHdP peptide achieved high affinity to bone mineral without interference in bioactivity, and local delivery of PTHdP from apatite materials could be a promising alternative for future bone tissue engineering.
一种新型的甲状旁腺激素衍生肽(PTHdP),其C端包含重复的天冬氨酸序列,N端含有磷酸化的丝氨酸,此前已被设计出来。为了评估其作为骨组织工程骨生长因子的潜力,本研究开发了一种结合纳米羟基磷灰石涂层和壳聚糖的真骨陶瓷(CH/TBC),作为一种理想的三维多孔递送载体。体外实验结果表明,PTHdP能够高效负载,并随后以可控和持续的方式从CH/TBC中释放出来。释放的PTHdP保留了生物活性,在MC3T3-E1细胞培养中,分别间歇性或连续性暴露时,能够对促进或抑制成骨作用产生显著影响。通过影像学和组织学检查在临界大小的兔桡骨缺损模型中评估,CH/TBC支架与PTHdP的组合显示出比对照组和纯CH/TBC组更强的刺激新骨形成的能力。这些结果表明,新型PTHdP肽对骨矿物质具有高亲和力且不干扰生物活性,从磷灰石材料局部递送PTHdP可能是未来骨组织工程的一种有前景的替代方法。