Phelps Edward A, Templeman Kellie L, Thulé Peter M, García Andrés J
Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA, 30332, USA.
Drug Deliv Transl Res. 2015 Apr;5(2):125-36. doi: 10.1007/s13346-013-0142-2.
Biofunctionalized polyethylene glycol maleimide (PEG-MAL) hydrogels were engineered as a platform to deliver pancreatic islets to the small bowel mesentery and promote graft vascularization. VEGF, a potent stimulator of angiogenesis, was incorporated into the hydrogel to be released in an on-demand manner through enzymatic degradation. PEG-MAL hydrogel enabled extended in vivo release of VEGF. Isolated rat islets encapsulated in PEG-MAL hydrogels remained viable in culture and secreted insulin. Islets encapsulated in PEG-MAL matrix and transplanted to the small bowel mesentery of healthy rats grafted to the host tissue and revascularized by 4 weeks. Addition of VEGF release to the PEG-MAL matrix greatly augmented the vascularization response. These results establish PEG-MAL engineered matrices as a vascular-inductive cell delivery vehicle and warrant their further investigation as islet transplantation vehicles in diabetic animal models.
生物功能化聚乙二醇马来酰亚胺(PEG-MAL)水凝胶被设计成一个平台,用于将胰岛递送至小肠系膜并促进移植物血管化。血管内皮生长因子(VEGF)是一种强大的血管生成刺激剂,被纳入水凝胶中,通过酶促降解以按需方式释放。PEG-MAL水凝胶能够在体内延长VEGF的释放。封装在PEG-MAL水凝胶中的分离大鼠胰岛在培养中保持存活并分泌胰岛素。封装在PEG-MAL基质中并移植到健康大鼠小肠系膜的胰岛移植到宿主组织并在4周时实现血管再生。向PEG-MAL基质中添加VEGF释放可大大增强血管化反应。这些结果确立了PEG-MAL工程化基质作为一种血管诱导性细胞递送载体,并保证在糖尿病动物模型中作为胰岛移植载体对其进行进一步研究。