Development of an off-the-shelf injectable MSC Microcarrier for Diabetic Wound Healing
Despite advances in wound care including bioengineered skin substitutes and negative pressure wound therapy, 1 in 4 patients with diabetic foot ulcers are likely to face amputation. Mesenchymal stem cell (MSC)-based therapies have shown promise in accelerating healing in proof-of-concept studies. However, past strategies have required on site cell culture facilities in order to prepare the MSC treatment. Our objective in this DiaComp Pilot and Feasibility application is to provide proof of concept for an off-the-shelf delivery method to enhance the viability of transplanted MSCs while maintaining their angiogenic and anti-inflammatory function. Our central hypothesis is that microcarriers will provide an effective cryopreservable microniche for MSCs resulting in improved survival of the cells as compared to those delivered in suspension and comparable function to those delivered without cryopreservation. We have recently developed a strategy to generate biodegradable ~100-400 µm diameter injectable microcarriers, each serving as an attachment point for hundreds of cells. The microcarriers have been designed to be biodegradable and able to withstand cryopreservation after seeding with MSCs. We expect delivery of MSCs on biodegradable injectable microcarriers to enhance MSCs potential to promote healing of diabetic wounds. The rationale underlying the proposed research is that by developing an off-the-shelf system for MSC delivery we will remove a significant hurdle to the widespread adoption of cell-therapy for diabetic wound healing. We plan the following specific aims: 1) Tune biodegradable injectable microcarriers to optimize cell loading, viability, function, and recovery after cryopreservation. 2) Pilot study to determine the ability of cryopreserved microcarriers to accelerate healing in an excisional diabetic wound model. This work will provide the basis for future R01 applications examining MSC microcarrier therapy in a mouse model of diabetic wounds and elucidation of mechanisms utilized by MSCs in vivo to promote healing.

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