Fabrication of micro-cryogels for therapeutic angiogenesis

Abstract

Peripheral artery disease is a most common symptom in diabetic patients. Recently, enhancing neo-vascular angiogenesis has been emerged as a promising therapeutic solution. Herein, we tried novel genetically edited stem cell delivery carrier as vascular endothelial growth factor (VEGF) transfected human tonsil derived mesenchymal stemcells (hTMSCs), which have been known as multipotent cells, within micro cryogel. Micro-cryogel was constructed with hyaluronic acid (HA) added poly ethylene glycol (PEG) which is reported as biocompatible. We dropped solution of hydrogel on initiated chemical vapor deposition (iCVD) processed hydrophobic surface. Hydrogel, then forms spherical structure, because of its own hydrophilicity. Chemically cross-linked gel were frozen and lyophilized. Manufactured cryogels were harvested and VEGF transfected cells were cultured within them. Transfection efficiency was controlled over 40%. Furthermore, size of cryogels could be controllable. VEGF secretion was confirmed with fluorescence measurement and quantified with VEGF ELISA assay. Culturing hTMSCS within gels not only prolonged VEGF releasing duration for several days but also maintained secretion level stably. Also, hTMSCs with PEG-HA cryogels demonstrated therapeutic effect on hindlimb ischemia model in vivo. Therefore, we suggest that our newly developed micro cryogel system could be a promising new remedy for not only diabetic but also all others who suffered from deteriorated blood perfusion.