Immunomodulatory biomaterials to promote early transplant integration and wound healing

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Sok, Mary Caitlin P.
Botchwey, Edward A.
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Ongoing advances in transplantation surgical techniques, together with improvements in immunosuppression regimens, have greatly reduced the rate of postoperative morbidity and graft loss. Despite these advances, wound complications due to systemic immunosuppression are a common post-transplant surgical complication. Therefore, there is a need for therapies that have the ability to allow for wound healing while also preventing rejection without the off-target side effects of systemic immunosuppression. One method that has the potential of mediating these complications is the delivery of immunomodulatory factors that are able to accelerate wound healing and tissue integration through the local recruitment and education of anti-inflammatory, pro-regenerative subsets of immune cells that work to enhance tissue regeneration and alloimmunity by dampening immune activation and cytokine production of factors involved in pathologic inflammation and rejection. We developed a hydrogel-based biomaterial system to deliver Aspirin-Triggered Resolvin D1 and Interleukin-10 in murine models of cutaneous injury and skin transplantation. We demonstrated that injured tissue can be enriched with anti-inflammatory, pro-angiogenic and pro-regenerative populations of neutrophils, monocytes, and macrophages. Dual delivery enhances the presence of tolerogenic dendritic cells and regulatory T cells in skin injury and in transplantation. This research presents a novel immunomodulatory hydrogel system that may aid in soft tissue regeneration by recruiting pro-regenerative immune cell subpopulations and stimulating vascularization after injury. These findings represent an improved understanding of how we may target pro-regenerative cells from different branches of the immune system, and this treatment has the potential to enhance tissue regeneration and prevent wound healing complications after skin tissue injury and lays the foundation for further exploration into the development of local immunomodulatory therapies to prevent graft rejection.
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