Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA.
Biomaterials. 2013 Jun;34(19):4602-11. doi: 10.1016/j.biomaterials.2013.03.012. Epub 2013 Mar 26.
Type 1 diabetes (T1DM) affects one in every 400 children and adolescents in the US. Due to the limitations of exogenous insulin therapy and whole pancreas transplantation, pancreatic islet transplantation has emerged as a promising therapy for T1DM. However, this therapy is severely limited by donor islet availability and poor islet engraftment and function. We engineered an injectable bio-synthetic, polyethylene glycol-maleimide hydrogel to enhance vascularization and engraftment of transplanted pancreatic islets in a mouse model of T1DM. Controlled presentation of VEGF-A and cell-adhesive peptides within this engineered material significantly improved the vascularization and function of islets delivered to the small bowel mesentery, a metabolically relevant site for insulin release. Diabetic mice receiving islets transplanted in proteolytically degradable hydrogels incorporating VEGF-A exhibited complete reversal of diabetic hyperglycemia with a 40% reduction in the number of islets required. Furthermore, hydrogel-delivered islets significantly improved weight gain, regulation of a glucose challenge, and intra-islet vascularization and engraftment compared to the clinical standard of islet infusion through the hepatic portal vein. This study establishes a simple biomaterial strategy for islet transplantation to promote enhanced islet engraftment and function.
1 型糖尿病（T1DM）影响美国每 400 名儿童和青少年中的 1 名。由于外源性胰岛素治疗和整个胰腺移植的限制，胰岛移植已成为 T1DM 的一种有前途的治疗方法。然而，这种治疗方法受到供体胰岛可用性和胰岛植入和功能差的严重限制。我们设计了一种可注射的生物合成的聚乙二醇-马来酰亚胺水凝胶，以增强 T1DM 小鼠模型中移植的胰岛的血管生成和植入。在这种工程材料中，VEGF-A 和细胞黏附肽的受控呈递显著改善了输送到小肠肠系膜的胰岛的血管生成和功能，这是胰岛素释放的代谢相关部位。接受 VEGF-A 结合蛋白水解可降解水凝胶中移植胰岛的糖尿病小鼠表现出糖尿病高血糖的完全逆转，所需胰岛数量减少了 40%。此外，与通过肝门静脉输注胰岛的临床标准相比，水凝胶递送的胰岛显著改善了体重增加、葡萄糖挑战的调节以及胰岛内血管生成和植入。这项研究建立了一种简单的胰岛移植生物材料策略，以促进增强的胰岛植入和功能。
