Distributed vasculogenesis from modular agarose-hydroxyapatite-fibrinogen microbeads.

摘要: Abstract Critical limb ischemia impairs circulation to the extremities, causing pain, disrupted wound healing, and potential tissue necrosis. Therapeutic angiogenesis seeks repair damaged microvasculature directly restore blood flow. In this study, we developed modular, micro-scale constructs designed possess robust handling qualities, allow in vitro pre-culture, promote formation. The microbead matrix consisted of an agarose (AG) base prevent aggregation, combined with cell-adhesive components fibrinogen (FGN) and/or hydroxyapatite (HA). Microbeads encapsulating a co-culture human umbilical vein endothelial cells (HUVEC) fibroblasts were prepared characterized. generally 80–100 µm diameter, size increased addition FGN HA. Addition HA yield microbeads, as well homogeneity distribution within matrix. Cell viability was high all types. When cell-seeded microbeads embedded fibrin hydrogels, HUVEC sprouting inosculation between neighboring observed over seven days. Pre-culture for additional days prior embedding resulted significantly greater network length AG + HA + FGN compared AG, AG + HA or AG + FGN microbeads. Importantly, composite more even widespread formation, relative control consisting pure fibrin. These results demonstrate that support both adjacent can distributed vascularization external Such modular microtissues may have utility treating ischemic by rapidly re-establishing microvascular network. Statement Significance (CLI) is chronic disease lead necrosis, amputation, death. Cell-based therapies are being explored flow complications CLI. small, non-aggregating agarose-hydroxyapatite-fibrinogen contained fibroblasts. easy handle culture, sprouts formed Our data demonstrates composition altered degree sprouting, format formulation therefore be useful developing revascularization strategies treatment disease.