Bioactive Injectable Hydrogels Containing Desferrioxamine and Bioglass for Diabetic Wound Healing

Diabetic wound is hard to heal mainly because of the difficulty in vascularization in the wound area. Accumulating results have shown that desferrioxamine (DFO) can promote secretion of hypoxia inducible factor-1 (HIF-1 alpha), thereby upregulating the expression of angiogenic growth factors and facilitating revascularization. Our preliminary study has demonstrated that Si ions in bioglass (BG) can upregulate vascular endothelial growth factor (VEGF) expression, thus promoting revascularization. It is hypothesized that the combined use of BG and DFO may have a synergistic effect in promoting VEGF expression and revascularization. To prove this, we first determined DFO concentration range that had no apparent cytotoxicity on human umbilical vein endothelial cells (HUVECs). Then, the optimal concentration of DFO promoting tube formation of HUVECs was determined by cell migration and tube formation assays. In addition, we demonstrated that combination use of BG and DFO improved the migration and tube formation of HUVECs as compared with the use of either BG or DFO alone as BG and DFO could synergistically upregulate VEGF expression. Furthermore, a sodium alginate hydrogel containing both BG and DFO was developed, and this hydrogel better facilitated diabetic skin wound healing than the use of either BG or DFO alone as BG and DFO in the hydrogels worked synergistically in promoting HIF-1 alpha and VEGF expression and subsequently vascularization in the wound sites. Therefore, in this study, the synergistic effect in promoting revascularization between BG and DFO was first demonstrated and an injectable hydrogel simultaneously containing BG and DFO was developed for enhancing repair of diabetic chronic skin defects by taking advantages of the synergistic effects of BG and DFO in promoting revascularization. The study opens up a new prospect for the development of skin repair-promoting biomaterials.