Department of Biomedical Engineering, University of Michigan, Ann Arbor, United States; Biointerfaces Institute, University of Michigan, Ann Arbor, United States
Department of Biomedical Engineering, University of Michigan, Ann Arbor, United States; Biointerfaces Institute, University of Michigan, Ann Arbor, United States
Emily C Wallace
Department of Biomedical Engineering, University of Michigan, Ann Arbor, United States
Bonnie D Spence
Department of Biomedical Engineering, University of Michigan, Ann Arbor, United States
Alec Eames
Department of Biomedical Engineering, University of Michigan, Ann Arbor, United States
Pamela Duran
Department of Biomedical Engineering, University of Michigan, Ann Arbor, United States; Biointerfaces Institute, University of Michigan, Ann Arbor, United States
Benjamin A Yang
Department of Biomedical Engineering, University of Michigan, Ann Arbor, United States; Biointerfaces Institute, University of Michigan, Ann Arbor, United States
Paula M Fraczek
Department of Biomedical Engineering, University of Michigan, Ann Arbor, United States; Biointerfaces Institute, University of Michigan, Ann Arbor, United States
Carol A Davis
Department of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, United States
Susan V Brooks
Department of Biomedical Engineering, University of Michigan, Ann Arbor, United States; Department of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, United States
Krishna Rao Maddipati
Department of Pathology, Lipidomics Core Facility, Wayne State University, Detroit, United States
Department of Biomedical Engineering, University of Michigan, Ann Arbor, United States; Biointerfaces Institute, University of Michigan, Ann Arbor, United States; Program in Cellular and Molecular Biology, University of Michigan, Ann Arbor, United States
The acute traumatic or surgical loss of skeletal muscle, known as volumetric muscle loss (VML), is a devastating type of injury that results in exacerbated and persistent inflammation followed by fibrosis. The mechanisms that mediate the magnitude and duration of the inflammatory response and ensuing fibrosis after VML remain understudied, and as such, the development of regenerative therapies has been limited. To address this need, we profiled how lipid mediators, which are potent regulators of the immune response after injury, varied with VML injuries that heal or result in fibrosis. We observed that non-healing VML injuries displayed increased pro-inflammatory eicosanoids and a lack of pro-resolving lipid mediators. Treatment of VML with a pro-resolving lipid mediator synthesized from docosahexaenoic acid, called Maresin 1, ameliorated fibrosis through reduction of neutrophils and macrophages and enhanced recovery of muscle strength. These results expand our knowledge of the dysregulated immune response that develops after VML and identify a novel immuno-regenerative therapeutic modality in Maresin 1.
