DescriptionChronic wounds are “stuck” in an inflammatory state characterized by hypoxia and high levels of inflammatory mediators such as inflammatory proteins, white blood cells and bacteria. The hostile environment of chronic wounds readily breaks down growth factors needed to promote wound healing. Recent studies have shown that mesenchymal stem/stromal cells (MSCs), which are non-hematopoietic stem cells, possess “anti-inflammatory” properties. These cells secrete factors that mitigate inflammation and promote wound healing of normal wounds. However, a major limitation with using MSCs is their ability to migrate away from the wound site. Therefore, we have generated a novel bioactive bandage made with alginate to immobilize the MSCs at the wound site. The goal of this project, unlike growth factor depots, is to have the MSCs provide sustained release of soluble factors to the wound and potentially modulate their secretion pattern depending on the wound environment. We hypothesize that MSCs can enhance wound healing by decreasing inflammation in the wound and increasing wound contraction to close the wound. This occurs through their secretion of different soluble factors lacking in chronic wounds and through communication with wound healing cells such as macrophages and fibroblasts. Our results show that the alginate microenvironment does not alter MSC viability or secretion. Immobilized MSCs increased wound closure rate in a diabetic mouse model. We observed that this enhancement could in part be due to the MSCs’ ability to promote differentiation of macrophages to the anti-inflammatory “M2” phenotype and differentiation of fibroblasts into α-smooth muscle actin myofibroblasts that deposit collagen and mediate wound contraction to close the wounds. In human chronic wounds, hypoxia may impair these responses; however, we found that MSCs were able to promote differentiation even in presence of hypoxic conditions.