Hierarchically Porous Microgels with Interior Spiral Canals for High-Efficiency Delivery of Stem Cells in Wound Healing

Abstract

Chronic wound poses a serious risk to diabetic patients, primarily due to damaged skin microvasculature and prolonged inflammation at the wound site. Mesenchymal stem cell (MSC) therapy utilizing microgels as a cell delivery system has shown promise in promoting wound healing by enhancing cell viability and the secretion of bioactive factors. Retaining sufficient MSCs at injury sites is crucial for optimal therapeutic outcomes. However, inadequate hierarchical structure and limited use of the microgel's interior space significantly reduce cell proliferation and infiltration efficiency, thereby compromising the therapeutic effect. To address this, a microfluidic approach is developed for fabricating porous hierarchical interconnected microgels with interior spiral canals (PHIGels) by employing a fluidic “viscous instability” effect and gas formation reaction during the microfluidic synthesis. These MSC-laden PHIGel scaffolds facilitate rapid proliferation and infiltration into the interior spiral canals through a hierarchical pore network, significantly increasing the number of viable cells that can be carried by the microgels. It is proved that these microgel-based deliveries of MSCs promote re-epithelialization, collagen synthesis, angiogenesis, and reduction in inflammation, thus enhancing cutaneous wound repair in a rat model of type I diabetes. The microporosity and hierarchical design of these microgels offer novel routes for tissue regeneration and repair.