PDF(Pubmed)
Abstract：
UNASSIGNED: The pleiotropic effect of fibroblast growth factor 2 (FGF2) on promoting myogenesis, angiogenesis, and innervation makes it an ideal growth factor for treating volumetric muscle loss (VML) injuries. While an initial delivery of FGF2 has demonstrated enhanced regenerative potential, the sustained delivery of FGF2 from scaffolds with robust structural properties as well as biophysical and biochemical signaling cues has yet to be explored for treating VML. The goal of this study is to develop an instructive fibrin microthread scaffold with intrinsic topographic alignment cues as well as regenerative signaling cues and a physiologically relevant, sustained release of FGF2 to direct myogenesis and ultimately enhance functional muscle regeneration.
UNASSIGNED: Heparin was passively adsorbed or carbodiimide-conjugated to microthreads, creating a biomimetic binding strategy, mimicking FGF2 sequestration in the extracellular matrix (ECM). It was also evaluated whether FGF2 incorporated into fibrin microthreads would yield sustained release. It was hypothesized that heparin-conjugated and co-incorporated (co-inc) fibrin microthreads would facilitate sustained release of FGF2 from the scaffold and enhance in vitro myoblast proliferation and outgrowth.
UNASSIGNED: Toluidine blue staining and Fourier transform infrared spectroscopy confirmed that carbodiimide-conjugated heparin bound to fibrin microthreads in a dose-dependent manner. Release kinetics revealed that heparin-conjugated fibrin microthreads exhibited sustained release of FGF2 over a period of one week. An in vitro assay demonstrated that FGF2 released from microthreads remained bioactive, stimulating myoblast proliferation over four days. Finally, a cellular outgrowth assay suggests that FGF2 promotes increased outgrowth onto microthreads.
UNASSIGNED: It was anticipated that the combined effects of fibrin microthread structural properties, topographic alignment cues, and FGF2 release profiles will facilitate the fabrication of a biomimetic scaffold that enhances the regeneration of functional muscle tissue for the treatment of VML injuries.
UNASSIGNED: Heparin was passively adsorbed or carbodiimide-conjugated to microthreads, creating a biomimetic binding strategy, mimicking FGF2 sequestration in the extracellular matrix (ECM). It was also evaluated whether FGF2 incorporated into fibrin microthreads would yield sustained release. It was hypothesized that heparin-conjugated and co-incorporated (co-inc) fibrin microthreads would facilitate sustained release of FGF2 from the scaffold and enhance in vitro myoblast proliferation and outgrowth.
UNASSIGNED: Toluidine blue staining and Fourier transform infrared spectroscopy confirmed that carbodiimide-conjugated heparin bound to fibrin microthreads in a dose-dependent manner. Release kinetics revealed that heparin-conjugated fibrin microthreads exhibited sustained release of FGF2 over a period of one week. An in vitro assay demonstrated that FGF2 released from microthreads remained bioactive, stimulating myoblast proliferation over four days. Finally, a cellular outgrowth assay suggests that FGF2 promotes increased outgrowth onto microthreads.
UNASSIGNED: It was anticipated that the combined effects of fibrin microthread structural properties, topographic alignment cues, and FGF2 release profiles will facilitate the fabrication of a biomimetic scaffold that enhances the regeneration of functional muscle tissue for the treatment of VML injuries.
摘要：
■成纤维细胞生长因子2（FGF2）促进肌生成的多效性作用，血管生成,和神经支配使其成为治疗体积肌肉损失（VML）损伤的理想生长因子。虽然FGF2的初始交付显示出增强的再生潜力，从具有稳健结构特性的支架持续递送FGF2以及生物物理和生化信号线索仍有待探索用于治疗VML。这项研究的目的是开发一种具有内在拓扑排列线索以及再生信号线索和生理相关的指导性纤维蛋白微丝支架，FGF2的持续释放以指导肌肉生成并最终增强功能性肌肉再生。
■肝素被动吸附或碳二亚胺缀合到微线上，创建仿生结合策略，模拟FGF2在细胞外基质（ECM）中的隔离。还评估了掺入纤维蛋白微线中的FGF2是否会产生持续释放。假设肝素缀合和共掺入(co-inc)的纤维蛋白微丝将促进FGF2从支架的持续释放并增强体外成肌细胞增殖和生长。
■甲苯胺蓝染色和傅里叶变换红外光谱证实,碳二亚胺缀合的肝素以剂量依赖性方式与纤维蛋白微丝结合。释放动力学显示肝素缀合的纤维蛋白微线在一周的时间内表现出FGF2的持续释放。体外试验表明，从微线释放的FGF2保持生物活性，刺激成肌细胞增殖超过四天。最后,细胞生长测定表明FGF2促进增加的生长到微线上。
■预期纤维蛋白微丝结构特性的综合作用，地形对齐提示，和FGF2释放曲线将促进仿生支架的制造,所述仿生支架增强用于治疗VML损伤的功能性肌肉组织的再生。
■肝素被动吸附或碳二亚胺缀合到微线上，创建仿生结合策略，模拟FGF2在细胞外基质（ECM）中的隔离。还评估了掺入纤维蛋白微线中的FGF2是否会产生持续释放。假设肝素缀合和共掺入(co-inc)的纤维蛋白微丝将促进FGF2从支架的持续释放并增强体外成肌细胞增殖和生长。
■甲苯胺蓝染色和傅里叶变换红外光谱证实,碳二亚胺缀合的肝素以剂量依赖性方式与纤维蛋白微丝结合。释放动力学显示肝素缀合的纤维蛋白微线在一周的时间内表现出FGF2的持续释放。体外试验表明，从微线释放的FGF2保持生物活性，刺激成肌细胞增殖超过四天。最后,细胞生长测定表明FGF2促进增加的生长到微线上。
■预期纤维蛋白微丝结构特性的综合作用，地形对齐提示，和FGF2释放曲线将促进仿生支架的制造,所述仿生支架增强用于治疗VML损伤的功能性肌肉组织的再生。
