Aligned protein-polymer composite fibers enhance nerve regeneration: A potential tissue-engineering platform
Aligned protein-polymer composite fibers enhance nerve regeneration: A potential tissue-engineering platform
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DOI：
10.1002/adfm.200600441
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发表时间：
2007-05-21
影响因子：
19
通讯作者：
Leong, Kam W.
中科院分区：
文献类型：
--
作者：
Chew, Sing Yian;Mi, Ruifa;Leong, Kam W.
从排列的聚合纤维中持续释放蛋白质在组织工程应用中具有巨大的潜力。这些蛋白质-聚合物复合纤维具有细胞附着的高表面积-体积比，并且可以提供生化和地形线索来增强组织再生。通过静电纺丝将己内酯和磷酸乙酯（PCLEEP）的共聚物与GDNF结合，制备了包裹人胶质细胞源性神经营养因子（GDNF, 0.13 wt%）的排列可生物降解聚合物纤维。蛋白质以聚集体的形式随机分散在整个聚合物基质中，并以持续的方式释放长达两个月。在大鼠周围神经损伤模型中测试了这些复合纤维的治疗效果。大鼠分为四组，一组接受空PCLEEP管（对照组）；1根纯PCLEEP静电纺丝管。纤维纵向排列（EF-L）或圆周排列（EF-C）；或有排列的GDNF-PCLEEP纤维的管（EF-L-GDNF）。三个月后，所有接受电纺丝神经导管的大鼠均观察到再生神经桥接了15mm的严重缺损间隙，而对照组为50%。EF-C组、EF-L组和EF-L- gdnf组分别有20%、33%和44%的大鼠出现电生理恢复，而对照组没有出现电生理恢复。这项研究表明，无需进一步修饰，普通电纺丝纤维可以帮助周围神经再生；然而，包封生长因子的协同作用促进了更显著的恢复。这项研究还展示了静电纺丝的新用途，将生化和地形线索结合到一个单一的植入物中，用于体内组织工程应用。
Sustained release of proteins from aligned polymeric fibers holds great potential in tissue-engineering applications. These protein-polymer composite fibers possess high surface-area-to-volume ratios for cell attachment, and can provide biochemical and topographic cues to enhance tissue regeneration. Aligned biodegradable polymeric fibers that encapsulate human glial cell-derived neurotrophic factor (GDNF, 0.13 wt%) were fabricated via electrospinning a copolymer of caprolactone and ethyl ethylene phosphate (PCLEEP) with GDNF. The protein was randomly dispersed throughout the polymer matrix in aggregate form, and released in a sustained manner for up to two months. The efficacy of these composite fibers was tested in a rat model for peripheral nerve-injury treatment. Rats were divided into four groups, receiving either empty PCLEEP tubes (control); 1 tubes with plain PCLEEP electrospun. fibers aligned longitudinally (EF-L) or circumferentially (EF-C); or tubes with aligned GDNF-PCLEEP fibers (EF-L-GDNF). After three months, bridging of a 15 mm critical defect gap by the regenerated nerve was observed in all the rats that received nerve conduits with electrospun fibers, as opposed to 50% in the control group. Electrophysiological recovery was seen in 20%, 33%, and 44% of the rats in the EF-C, EF-L, and EF-L-GDNF groups respectively, whilst none was observed in the controls. This study has demonstrated that, without further modification, plain electrospun fibers can help in peripheral nerve regeneration; however, the synergistic effect of an encapsulated growth factor facilitated a more significant recovery. This study also demonstrated the novel use of electrospinning to incorporate biochemical and topographical cues into a single implant for in vivo tissue-engineering applications.