Zhang Zhan-Zhao, Song Lu, Zhang Zhi-Yong, Lv Ming-Ming
Shanghai Key Laboratory of Tissue Engineering, Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University Shanghai, PR China.
Department of Neurology, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University Shanghai, PR China.
Int J Clin Exp Pathol. 2017 Sep 1;10(9):10019-10031. eCollection 2017.
Since diabetes lead to alterations in bone metabolism with reductions in bone mineral content and delayed bone formation, the most effective method for bone regeneration in diabetes remains to be determined. In this study, type 2 diabetes were successfully induced via a high-fat diet and low-dose streptozotocin intraperitoneal injection. Excess reactive oxygen species (ROS) has been implicated in diabetes mellitus. Overexpression of ROS can lead to oxidative stress and subsequently to HO-mediated impaired proliferation and delayed cellular differentiation. As a result, antioxidant alpha-lipoic acid (ALA)-loaded poly (lactic-co-glycolic acid) (PLGA) microspheres were fabricated using the emulsion solvent evaporation method, and a sustained and controlled release of ALA was observed up to 27 days. It was demonstrated that biodegradable PLGA microspheres loaded with ALA acted as ROS scavengers and partially recover the mesenchymal stem cell proliferation and differentiation. The bone formation of ALA loaded scaffolds in rat cranial bone defects were greater than the prime three-dimensional collagen scaffold. These results suggest the application of ALA loaded PLGA microsphere exhibit good bioactivity and bone forming ability in diabetes.
由于糖尿病会导致骨代谢改变，骨矿物质含量降低且骨形成延迟，因此糖尿病患者骨再生的最有效方法仍有待确定。在本研究中，通过高脂饮食和低剂量链脲佐菌素腹腔注射成功诱导出2型糖尿病。过量的活性氧（ROS）与糖尿病有关。ROS的过表达会导致氧化应激，进而导致HO介导的增殖受损和细胞分化延迟。因此，采用乳液溶剂蒸发法制备了负载抗氧化剂α-硫辛酸（ALA）的聚乳酸-羟基乙酸共聚物（PLGA）微球，并观察到ALA持续可控释放长达27天。结果表明，负载ALA的可生物降解PLGA微球可作为ROS清除剂，并部分恢复间充质干细胞的增殖和分化。负载ALA的支架在大鼠颅骨缺损处的骨形成大于原始的三维胶原支架。这些结果表明，负载ALA的PLGA微球在糖尿病中具有良好的生物活性和骨形成能力。
