Nath Subrata D, Linh Nguyen T B, Sadiasa Alexander, Lee Byong T
Department of Biomedical Engineering and Materials, Soonchunhyang University, Republic of Korea.
J Biomater Appl. 2014 Apr;28(8):1151-63. doi: 10.1177/0885328213499272. Epub 2013 Sep 12.
The main objective of this study was to fabricate a controlled drug delivery which is simultaneously effective for bone regeneration. We have encapsulated simvastatin, which enhances osteoblastic activity, in the poly (lactic-co-glycolic acid) microspheres. Loading of these microspheres inside the spongy scaffold of biphasic calcium phosphate with the help of Gelatin (Gel) hydrogel controls the delivery of the drug, and ensures a more favorable drug release profile. As a result, some significant benefits have been achieved, such as higher mechanical strength, excellent biocompatibility in in vitro experiments. For determining the characteristics of the composite scaffold, several analysis, such as scanning electron microscope, EDX, X-ray diffraction, FT-IR, and porosity were carried out. The in vitro drug release profile clearly indicates that simvastatin release from the microsphere was more controlled and prolonged after loading in the scaffold. Biocompatibility was certainly higher for the final composite scaffold compared to drug unloaded scaffold, as assessed through MTT assay and Confocal imaging with MC3T3-E1 pre-osteoblast cells. Cell attachment and proliferation were certainly higher in the presence of drug loaded microspheres. Bone remodeling gene and protein expression were observed by real-time polymerase chain reaction and Western blot respectively. Simvastatin loaded scaffold exhibited the best results in every determination which was carried out.
本研究的主要目的是制备一种对骨再生同时有效的控释药物制剂。我们已将增强成骨细胞活性的辛伐他汀包裹在聚(乳酸-乙醇酸)微球中。借助明胶(Gel)水凝胶将这些微球负载到双相磷酸钙的海绵支架内,可控制药物的释放,并确保更有利的药物释放曲线。结果,取得了一些显著的益处,例如在体外实验中具有更高的机械强度、优异的生物相容性。为了确定复合支架的特性,进行了几种分析,如扫描电子显微镜、能谱分析、X射线衍射、傅里叶变换红外光谱和孔隙率分析。体外药物释放曲线清楚地表明,将微球负载到支架中后,辛伐他汀从微球中的释放更可控且持续时间更长。通过MTT法和与MC3T3-E1前成骨细胞的共聚焦成像评估,最终复合支架的生物相容性肯定高于未负载药物的支架。在存在负载药物的微球的情况下,细胞附着和增殖肯定更高。分别通过实时聚合酶链反应和蛋白质印迹观察骨重塑基因和蛋白质表达。在进行的各项测定中,负载辛伐他汀的支架均表现出最佳结果。