The objective of this study was to design an injectable biomaterial system that becomes porous in situ to deliver and control vascular progenitor cell release. Alginate hydrogels were loaded with outgrowth endothelial cells (OECs) and alginate lyase, an enzyme which cleaves alginate polymer chains. We postulated and confirmed that higher alginate lyase concentrations mediated loss of hydrogel mechanical properties. Hydrogels incorporating 5 and 50 mU/mL of alginate lyase experienced approximately 28% and 57% loss of mass as well as 81% and 91% reduction in storage modulus respectively after a week. Additionally, computational methods and mechanical analysis revealed that hydrogels with alginate lyase significantly increased in mesh size over time. Furthermore, alginate lyase was not found to inhibit OEC proliferation, viability or sprouting potential. Finally, alginate hydrogels incorporating OECs and alginate lyase promoted up to nearly a 10 fold increase in OEC migration in vitro than nondegradable hydrogels over the course of a week and increased functional vasculature in vivo via a chick chorioallantoic membrane (CAM) assay. Overall, these findings demonstrate that alginate lyase incorporated hydrogels can provide a simple and robust system to promote controlled outward cell migration into native tissue for potential therapeutic revascularization applications.

本研究的目的是设计一种可注射的生物材料系统，该系统在原位变得多孔，以输送和控制血管祖细胞的释放。海藻酸盐水凝胶负载有生长的内皮细胞（OEC）和海藻酸盐裂解酶（一种裂解海藻酸盐聚合物链的酶）。我们假设并证实较高的藻酸盐裂解酶浓度会介导水凝胶机械性能的损失。一周后，掺入 5 mU/mL 和 50 mU/mL 海藻酸裂解酶的水凝胶分别经历了大约 28% 和 57% 的质量损失以及 81% 和 91% 的储能模量降低。此外，计算方法和机械分析表明，随着时间的推移，含有藻酸盐裂解酶的水凝胶的网眼尺寸显着增加。此外，没有发现藻酸盐裂解酶会抑制 OEC 增殖、活力或发芽潜力。最后，在一周内，掺有 OEC 和藻酸盐裂解酶的藻酸盐水凝胶在体外促进 OEC 迁移量比不可降解水凝胶增加近 10 倍，并通过鸡绒毛尿囊膜 (CAM) 测定增加体内功能性脉管系统。总的来说，这些发现表明，掺有藻酸盐裂解酶的水凝胶可以提供一个简单而强大的系统，以促进受控的细胞向外迁移到天然组织中，以用于潜在的治疗性血运重建应用。