Department of Bioengineering, Rice University, Houston, TX 77251-1892, USA.
Biomaterials. 2010 May;31(14):4146-56. doi: 10.1016/j.biomaterials.2010.01.112. Epub 2010 Feb 13.
The use of a strategy involving space maintenance as the initial step of a two-stage regenerative medicine approach toward reconstructing significant bony or composite tissue defects in the craniofacial area, preserves the void volume of bony defects and could promote soft tissue healing prior to the subsequent definitive repair. One of the complications with a biomaterial-based space maintenance approach is local infection, which requires early, effective eradication, ideally through local antibiotic delivery. The purpose of this study is to develop a dual function implant material for maintaining osseous space and releasing an antibiotic to eliminate local infection in bony defects. Colistin, a polymyxin antibiotic, was chosen specifically to address infections with Acinetobacter species, the most common pathogen associated with combat-related traumatic craniofacial injuries. Porous polymethylmethacrylate (PMMA) constructs incorporating poly(lactic-co-glycolic acid) (PLGA) microspheres were fabricated by mixing a clinically used bone cement formulation of PMMA powder and methylmethacrylate liquid with a carboxymethylcellulose (CMC) hydrogel (40 or 50 wt%) to impart porosity and PLGA microspheres (10 or 15 wt%) loaded with colistin to control drug release. The PMMA/CMC/PLGA construct featured mild setting temperature, controllable surface/bulk porosity by incorporation of the CMC hydrogel, reasonably strong compressive properties, and continuous drug release over a period of 5 weeks with total drug release of 68.1-88.3%, depending on the weight percentage of CMC and PLGA incorporation. The concentration of released colistin was well above its reported minimum inhibitory concentration against susceptible species for 5 weeks. This study provides information on the composition parameters that enable viable porosity characteristics/drug release kinetics of the PMMA/CMC/PLGA construct for the initial space maintenance as part of a two-stage regenerative medicine approach.
在颅面区域重建重大骨或复合组织缺损的两阶段再生医学方法中,采用涉及空间维持的策略作为初始步骤,可以保留骨缺损的空隙体积,并在随后的确定性修复之前促进软组织愈合。基于生物材料的空间维持方法的并发症之一是局部感染,需要早期、有效根除,理想情况下通过局部抗生素输送来实现。本研究旨在开发一种双重功能植入物材料,用于维持骨空间并释放抗生素以消除骨缺损中的局部感染。多粘菌素抗生素粘菌素被特别选择用于解决与战斗相关的创伤性颅面损伤相关的不动杆菌属物种引起的感染。通过将临床使用的 PMMA 粉末和甲基丙烯酸甲酯液体与羧甲基纤维素 (CMC) 水凝胶(40 或 50wt%)混合来制备掺入聚乳酸-共-羟基乙酸(PLGA)微球的多孔聚甲基丙烯酸甲酯(PMMA)构建体,以赋予多孔性和载有粘菌素的 PLGA 微球(10 或 15wt%)来控制药物释放。PMMA/CMC/PLGA 构建体具有温和的凝固温度、通过掺入 CMC 水凝胶可控制的表面/体多孔性、合理的抗压性能以及在 5 周内持续释放药物,总药物释放率为 68.1-88.3%,具体取决于 CMC 和 PLGA 的重量百分比。释放的粘菌素浓度在 5 周内一直高于其对敏感物种的报告最小抑菌浓度。本研究提供了有关组成参数的信息,这些参数使 PMMA/CMC/PLGA 构建体具有可行的孔隙率特征/药物释放动力学,可作为两阶段再生医学方法的初始空间维持的一部分。