Department of Orthopedics, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, People's Republic of China.
School of Mechanical Engineering, Shanghai Jiao Tong University, State Key Laboratory of Mechanical System and Vibration, Shanghai 200240, People's Republic of China.
Biomaterials. 2014 Aug;35(26):7259-70. doi: 10.1016/j.biomaterials.2014.05.028. Epub 2014 Jun 6.
Composited Chitosan/Hydroxyapatite (CS/HA) material coated on titanium surface (cTi) is a promising approach to produce biomaterials with better osseointegration capacity, but its bio-performance under diabetic conditions and the mechanisms involved remain elusive. We propose that the alterations in the Wnt/β-catenin pathway may play a role in mediating the improvement effect of cTi on diabetes-induced impaired implant osteointegration. To confirm the hypothesis, primary rat osteoblasts incubated on Ti and cTi were subjected to normal serum (NS), diabetic serum (DS), DS + Wnt3a (a specific Wnt agonist) and DS + Dkk1 (a specific Wnt antagonist) treatment. In vivo study was performed on diabetic sheep implanted with Ti or cTi into the bone defect on crista iliaca. Results showed that diabetes depressed osteoblast function evidenced by impaired cell adhesion and morphology, decreased cell proliferation and ALP activity, and higher apoptotic rate on Ti. Importantly, both cTi and Wnt3a treatment ameliorated osteoblastic dysfunction and apoptosis under diabetic condition. Implantation with cTi significantly improved osteointegration evidenced by Micro-CT and histological examinations compared with Ti. Moreover, the aforementioned promotive effects afforded by cTi were abolished by blocking Wnt pathway with Dkk1. Our study explicitly demonstrates that CS/HA composite material improves diabetes-induced impaired osteointegration of Ti via the reactivation of Wnt/β-catenin pathway and provides a target point for biomaterial modification to attain better clinical performance in diabetic patients.
壳聚糖/羟基磷灰石（CS/HA）复合材料涂覆于钛表面（cTi）是一种很有前途的方法，可以生产出具有更好骨整合能力的生物材料，但它在糖尿病条件下的生物性能及其相关机制仍不清楚。我们提出，Wnt/β-连环蛋白途径的改变可能在介导 cTi 改善糖尿病引起的植入物骨整合受损中发挥作用。为了验证这一假设，将原代大鼠成骨细胞在 Ti 和 cTi 上孵育，然后用正常血清（NS）、糖尿病血清（DS）、DS+Wnt3a（一种特定的 Wnt 激动剂）和 DS+Dkk1（一种特定的 Wnt 拮抗剂）处理。在植入 Ti 或 cTi 到髂嵴骨缺损的糖尿病绵羊体内进行了体内研究。结果表明，糖尿病抑制了成骨细胞的功能，表现在细胞黏附形态受损、细胞增殖和 ALP 活性降低以及 Ti 上的凋亡率增加。重要的是，cTi 和 Wnt3a 处理均可改善糖尿病条件下成骨细胞的功能障碍和凋亡。与 Ti 相比，cTi 植入显著改善了骨整合，通过 Micro-CT 和组织学检查得到证实。此外，用 Dkk1 阻断 Wnt 途径可消除 cTi 提供的上述促进作用。我们的研究明确表明，CS/HA 复合材料通过重新激活 Wnt/β-连环蛋白途径改善了糖尿病引起的 Ti 植入物骨整合受损，并为生物材料改性提供了一个靶点，以在糖尿病患者中获得更好的临床性能。
