Xiang Geng, Liu Keyin, Wang Tianji, Hu Xiaofan, Wang Jing, Gao Zhiheng, Lei Wei, Feng Yafei, Tao Tiger H
Department of Orthopedics Xijing Hospital The Fourth Military Medical University Xi'an 710032 China.
State Key Laboratory of Transducer Technology Shanghai Institute of Microsystem and Information Technology Chinese Academy of Sciences Shanghai 200050 China.
Adv Sci (Weinh). 2020 Dec 16;8(3):2002328. doi: 10.1002/advs.202002328. eCollection 2021 Feb.
As a chronic inflammatory disease, diabetes mellitus creates a proinflammatory microenvironment around implants, resulting in a high rate of implant loosening or failure in osteological therapies. In this study, macroporous silk gel scaffolds are injected at the bone-implant interface for in situ release of sitagliptin that can regulate macrophage response to create a prohealing microenvironment in diabetes mellitus disease. Notably, it is discovered that sitagliptin induces macrophage polarization to the M2 phenotype and alleviates the impaired behaviors of osteoblasts on titanium (Ti) implants under diabetic conditions in a dose-dependent manner. The silk gel scaffolds loaded with sitagliptin elicite a stronger recruitment of M2 macrophages to the sites of Ti implants and a significant promotion of osteointegration, as compared to oral sitagliptin administration. The results suggest that injectable silk/sitagliptin gel scaffolds can be utilized to modulate the immune responses at the bone-implant interface, thus enhancing bone regeneration required for successful implantation of orthopedic and dental devices in diabetic patients.
作为一种慢性炎症性疾病，糖尿病会在植入物周围形成促炎微环境，导致骨科学治疗中植入物松动或失败的发生率很高。在本研究中，将大孔丝凝胶支架注射到骨-植入物界面，用于西他列汀的原位释放，该药物可调节巨噬细胞反应，在糖尿病疾病中创造促进愈合的微环境。值得注意的是，发现西他列汀以剂量依赖的方式诱导巨噬细胞极化为M2表型，并减轻糖尿病条件下钛（Ti）植入物上成骨细胞的受损行为。与口服西他列汀相比，负载西他列汀的丝凝胶支架能更强烈地将M2巨噬细胞募集到Ti植入物部位，并显著促进骨整合。结果表明，可注射的丝/西他列汀凝胶支架可用于调节骨-植入物界面的免疫反应，从而增强糖尿病患者成功植入骨科和牙科器械所需的骨再生。
