Hu Xiao-Fan, Feng Ya-Fei, Xiang Geng, Lei Wei, Wang Lin
Department of Orthopedics, Xijing Hospital, The Fourth Military Medical University, Xi'an 710032, P. R. China.
J Mater Chem B. 2018 Apr 21;6(15):2274-2288. doi: 10.1039/c7tb03247a. Epub 2018 Mar 28.
The diabetes-related high failure risk for endosseous implants needs efficacious methods to improve osteointegration on the bone-implant interface (BII). Poly(lactic-co-glycolic) acid (PLGA) is widely used in tissue engineering but its effects on the BII in diabetes remain unclear. To clarify this issue, 3D-printed porous titanium implants (TI) with and without PLGA coating were fixed in the bone defects of sheep in vivo, and vascular endothelial cells (VEC) and osteoblasts were incubated on the implant surface under normal conditions (NC) and diabetic conditions (DC) in vitro. The results showed that the PLGA coating promoted angiogenesis on the BII and the osteointegration of TI in diabetic sheep. The PLGA coating attenuated the DC-induced dysfunctions of VEC but not of osteoblasts. When VEC and osteoblasts were co-cultured in DC, the PLGA coating showed protective effects on the osteoblasts. Lactic acid (LA) but not glycolic acid (GA), both of which are degradation products of PLGA, induced similar effects to those of PLGA. These results suggest that PLGA coating on TI could promote angiogenesis in diabetes by its degradation production of LA, thus indirectly improving the bone formation on BII. Furthermore, PLGA exerted its effects, at least partially, through inhibiting the pathological effects of advanced glycation end products (AGEs) on the BII. This is the first study of the effects of PLGA on angiogenesis on the BII and the first findings on the inhibitory effects of PLGA on AGEs. Our findings demonstrate that PLGA is a promising interface-modification component for fabricating implants with better angiogenesis and osteointegration on the BII under diabetic conditions. This strategy might be applicable for reducing implant failure in diabetic patients.
骨内植入物与糖尿病相关的高失败风险需要有效的方法来改善骨-植入物界面（BII）的骨整合。聚乳酸-乙醇酸共聚物（PLGA）在组织工程中被广泛应用，但其对糖尿病患者BII的影响仍不清楚。为了阐明这个问题，将有或没有PLGA涂层的3D打印多孔钛植入物（TI）体内固定在绵羊的骨缺损处，并在体外正常条件（NC）和糖尿病条件（DC）下将血管内皮细胞（VEC）和成骨细胞接种在植入物表面。结果表明，PLGA涂层促进了糖尿病绵羊BII的血管生成和TI的骨整合。PLGA涂层减轻了DC诱导的VEC功能障碍，但没有减轻成骨细胞的功能障碍。当VEC和成骨细胞在DC中共培养时，PLGA涂层对成骨细胞具有保护作用。PLGA的降解产物乳酸（LA）而非乙醇酸（GA）诱导了与PLGA相似的作用。这些结果表明，TI上的PLGA涂层可通过其降解产物LA促进糖尿病中的血管生成，从而间接改善BII上的骨形成。此外，PLGA至少部分地通过抑制晚期糖基化终产物（AGEs）对BII的病理作用发挥其作用。这是关于PLGA对BII血管生成影响的首次研究，也是关于PLGA对AGEs抑制作用的首次发现。我们的研究结果表明，PLGA是一种有前途的界面修饰成分，可用于制造在糖尿病条件下在BII上具有更好血管生成和骨整合的植入物。这种策略可能适用于减少糖尿病患者的植入物失败。
