RESUMEN
Disruption of the reparative process, often found in diabetic patients, results in chronic, non-healing wounds that significantly impact a patient's quality of life. This highlights the need of new therapeutic options to improve the healing of diabetic wounds. In this study, we focused on developing a cell-free hydrogel dressing loaded with mesenchymal stem cell (MSC)-conditioned media (CM) to potentially improve the healing of hard-to-heal wounds. We simulated a hyperglycemic environment by incubating human dermal fibroblasts in a high glucose environment (30 mM) and validated that MSC-CM rescued the impaired functions (proliferation and migration) of hyperglycemic fibroblasts. Further, we investigated the effect of loading MSC-CM in gelatin methacrylate (GelMA)-poly (ethylene glycol) diacrylate (PEGDA) hybrid hydrogels in improving the proliferative activity of glucose-treated fibroblasts. The controlled release of bioactive factors from MSC-CM loaded GelMA-PEGDA hydrogels promoted the metabolic activity of hyperglycemic fibroblasts. In addition, the growth rate of hyperglycemic fibroblasts was found to be similar to that of normal fibroblasts. Our observations, thus, suggest the potential application of cell-free, MSC-secretome-loaded hydrogel in the healing of diabetic or chronic wounds.
RESUMEN
Mesenchymal stem cell (MSC)-based therapy for promoting vascular regeneration is a promising strategy for treating ischemic diseases. However, low engraftment and retention rate of MSCs at the target site highlights the importance of paracrine signaling of MSCs in the reparative process. Thus, harnessing MSC-secretome is essential for rational design of MSC-based therapies. The role of microenvironment in regulating the paracrine signaling of MSCs is not well known. In this study, human bone marrow-derived MSCs were seeded on matrices with varying stiffness or cell adhesive sites, and conditioned media was collected. The concentrations of angiogenic molecules in the media was measured via ELISA. In addition, the bioactivity of the released molecules was investigated via assessing the proliferation and capillary morphogenesis of human umbilical vein endothelial cells (HUVECs) incubated with conditioned media. Our study revealed that secretion of vascular endothelial growth factor (VEGF) is dependent on substrate stiffness. Maximal secretion was observed when MSCs were seeded on hydrogel matrices of 5.0â¯kPa stiffness. Proliferation and tubulogenesis of HUVECs supported ELISA data. On the other hand, variation of cell adhesive sites while maintaining a uniform optimal stiffness, did not influence the pro-angiogenic activity of MSCs.