PCL-fibrin-alginate hydrogel based cell co-culture system for improving angiogenesis and immune modulation in limb ischemia

Stem cell therapy has demonstrated promise in regenerative medicine due to their ability to differentiate into various cell types and secrete growth factors. However, challenges such as poor survival rate of transplanted cells under ischemic and immune conditions limit its effectiveness. To address these issues, we developed a polycaprolactone (PCL)-fibrin-alginate matrix hydrogel, which combines adipose-derived stem cells and human umbilical vein endothelial cells with a PCL fiber, encapsulated within fibrin and alginate hydrogel to enhance cell survival, proliferation, and immune modulation. This structure offers protection to the encapsulated cells, supports angiogenesis, and modulates the immune response, significantly improving therapeutic outcomes in a mouse model of hindlimb ischemia. Our in vitro and in vivo results demonstrate the scaffold's ability to support cell viability, promote angiogenesis, and modulate inflammatory responses, indicating its potential as a promising platform for ischemic tissue repair and regenerative medicine. This innovative approach to cell-based therapy highlights the importance of scaffold design in enhancing the therapeutic efficacy of stem cell treatments for ischemic diseases.