Bliley J M, Sivak W N, Minteer D M, Tompkins-Rhoades C, Day J, Williamson G, Liao H T, Marra K G
Division of Trauma Plastic Surgery, Department of Plastic and Reconstructive Surgery, Craniofacial Research Center, Chang Gung Memorial Hospital, Chang Gung University, Taiwan, R.O.C.
McGowan Institute for Regenerative Medicine, Pittsburgh, Pennsylvania, United States.
ACS Biomater Sci Eng. 2015 Jul 13;1(7):504-512. doi: 10.1021/ab5001518. Epub 2015 Jun 17.
Synthetic nerve guides are widely utilized to reconstruct peripheral nerve defects that are less than three centimeters. However, there are no clinically available nerve guides that are approved to promote repair over long gaps (>3 cm). Many currently available guides are unable to sustain large defect regeneration either because of limitations in fabrication or short degradation times in vivo. Furthermore, current clinically available nerve guides do not contain neurotrophic factor delivery systems to promote nerve tissue regeneration over long gaps. The purpose of this paper is to describe the manufacturing parameters and sterilization procedures of a 5.2 cm poly(caprolactone) nerve conduit with embedded polymeric microspheres that encapsulate glial cell line-derived neurotrophic factor (GDNF) for implantation into a preclinical 5 cm median nerve defect model. Nerve conduits were sterilized with room temperature ethylene oxide (RT EtO) and assessed for morphology as well as maintenance of porosity. Release kinetics and bioactivity of GDNF were also assessed in RT EtO sterilized guides. Scanning electron microscopy indicated that RT EtO treatment did not affect morphology and porosity percentage of nerve guides. Furthermore, RT EtO had no effect on GDNF bioactivity based on Schwannoma cell migration studies. RT EtO guides exhibited significantly slowed GDNF release compared to GDNF release from nonsterile guides indicating that EtO treatment may enhance the long-term delivery kinetics of GDNF from polymeric microspheres within the nerve guide.
合成神经导管被广泛用于修复长度小于三厘米的周围神经缺损。然而，目前尚无经临床批准可促进长间隙（>3厘米）修复的神经导管。由于制造工艺的限制或体内降解时间短，许多现有的导管无法维持大缺损的神经再生。此外，目前临床上可用的神经导管不包含神经营养因子递送系统，无法促进长间隙的神经组织再生。本文旨在描述一种5.2厘米长的聚己内酯神经导管的制造参数和灭菌程序，该导管嵌入了包裹胶质细胞源性神经营养因子（GDNF）的聚合物微球，用于植入临床前5厘米正中神经缺损模型。神经导管用室温环氧乙烷（RT EtO）进行灭菌，并评估其形态以及孔隙率的维持情况。还在RT EtO灭菌的导管中评估了GDNF的释放动力学和生物活性。扫描电子显微镜表明，RT EtO处理不影响神经导管的形态和孔隙率百分比。此外，基于雪旺瘤细胞迁移研究，RT EtO对GDNF生物活性没有影响。与未灭菌导管释放的GDNF相比，RT EtO处理的导管中GDNF的释放明显减慢，这表明环氧乙烷处理可能会增强神经导管内聚合物微球中GDNF的长期释放动力学。
