Centre for Translational Medicine Research & Development, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, PR China; Key Laboratory of Health Informatics, Chinese Academy of Sciences, PR China.
Centre for Translational Medicine Research & Development, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, PR China; Musculoskeletal Research Laboratory, Department of Orthopaedics & Traumatology, The Chinese University of Hong Kong, Hong Kong SAR, PR China.
Biomaterials. 2019 Mar;197:207-219. doi: 10.1016/j.biomaterials.2019.01.013. Epub 2019 Jan 7.
Bone defect repair is a challenging clinical problem in musculoskeletal system, especially in orthopaedic disorders such as steroid associated osteonecrosis (SAON). Magnesium (Mg) as a biodegradable metal with properly mechanical properties has been investigating for a long history. In this study, Mg powder, poly (lactide-co-glycolide) (PLGA), β-tricalcium phosphate (β-TCP) were the elements to formulate a novel porous PLGA/TCP/Mg (PTM) scaffolds using low temperature rapid prototyping (LT-RP) technology. The physical characterization of PTM scaffold and Mg ions release were analyzed in vitro. The osteogenic and angiogenic properties of PTM scaffolds, as well as the biosafety after implantation were assessed in an established SAON rabbit model. Our results showed that the PTM scaffold possessed well-designed bio-mimic structure and improved mechanical properties. Findings of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and micro-computed tomography (micro CT)-based angiography indicated that PTM scaffold could increase blood perfusion and promote new vessel ingrowth at 4 weeks after surgery, meanwhile, a plenty of newly formed vessels with well-architective structure were observed at 8 weeks. Correspondingly, at 12 weeks after surgery, micro-CT, histological and mechanical properties analysis showed that PTM could significant enhance new bone formation and strengthen newly formed bone mechanical properties. The mean bone volume in PTM group was 56.3% greater than that in PT group. Biosafety assessments from 0 to 12 weeks after implantation did not induce increase in serum Mg ions concentration, and immune response, liver and kidney function parameters were all at normal level. These findings suggested that the PTM scaffold had both osteogenic and angiogenic abilities which were synergistic effect in enhancing new bone formation and strengthen newly formed bone quality in SAON. In summary, PTM scaffolds are promising composite biomaterials for repairing challenging bone defect that would have great potential for its clinical translation.
骨缺损修复是肌肉骨骼系统中的一个具有挑战性的临床问题,特别是在骨科疾病如类固醇相关骨坏死(SAON)中。镁(Mg)作为一种具有适当机械性能的可生物降解金属,已经被研究了很长时间。在这项研究中,Mg 粉末、聚(乳酸-共-乙醇酸)(PLGA)、β-磷酸三钙(β-TCP)被用来通过低温快速成型(LT-RP)技术来制备一种新型多孔 PLGA/TCP/Mg(PTM)支架。体外分析了 PTM 支架的物理特性和 Mg 离子释放情况。在建立的 SAON 兔模型中,评估了 PTM 支架的成骨和血管生成特性以及植入后的生物安全性。我们的结果表明,PTM 支架具有设计良好的仿生结构和改善的机械性能。动态对比增强磁共振成像(DCE-MRI)和基于微计算机断层扫描(micro CT)的血管造影结果表明,PTM 支架可以在手术后 4 周增加血液灌注并促进新血管生长,同时在 8 周时观察到大量具有良好结构的新形成的血管。相应地,在手术后 12 周时,micro CT、组织学和机械性能分析表明,PTM 可以显著增强新骨形成并增强新形成骨的机械性能。PTM 组的平均骨体积比 PT 组大 56.3%。从植入后 0 周到 12 周的生物安全性评估没有引起血清 Mg 离子浓度升高,免疫反应、肝功能和肾功能参数均处于正常水平。这些发现表明,PTM 支架具有成骨和血管生成能力,两者协同作用可增强新骨形成并增强 SAON 中新形成骨的质量。总之,PTM 支架是一种有前途的复合生物材料,可用于修复具有挑战性的骨缺损,具有很大的临床转化潜力。