Sergei Butenko1,2,12, Hiromi Miwa3,12, Yingzi Liu2, Maksim V. Plikus2,4,5,6, Phillip O. Scumpia7,8 and Wendy F. Liu1,9,10,11 1Department of Biomedical Engineering, University of California Irvine, Irvine, California, USA 2Department of Developmental and Cell Biology, University of California Irvine, Irvine, California, USA 3Department of Bioengineering, University of California Los Angeles, Los Angeles, California, USA 4Sue and Bill Gross Stem Cell Research Center, University of California Irvine, Irvine, California, USA 5NSF-Simons Center for Multiscale Cell Fate Research, University of California Irvine, Irvine, California, USA 6Center for Complex Biological Systems, University of California Irvine, Irvine, California, USA 7Department of Medicine, Division of Dermatology, University of California Los Angeles, Los Angeles, California, USA 8Department of Dermatology, Greater Los Angeles VAMC, Los Angeles, California, USA 9UCI Edwards Lifesciences Foundation Cardiovascular Innovation and Research Center (CIRC), University of California Irvine, Irvine, California, USA 10Molecular Biology and Biochemistry, University of California Irvine, Irvine, California, USA 11Institute for Immunology, University of California Irvine, Irvine, California, USA Correspondence: wendy.liuuci.edu

↵12 These authors contributed equally to this work.

The healing of human skin wounds is designed for a rapid fibroproliferative response at the expense of tissue complexity and is therefore prone to scar formation. Moreover, wound healing often goes awry when excessive inflammation leads to chronic nonhealing wounds or when excessive repair results in uncontrolled tissue fibrosis. The immune system plays a central role in orchestrating wound healing, and, thus, controlling immune cell activities holds great potential for reducing scars and enhancing regeneration. Biomaterial dressings directly interact with immune cells in the wound and have been shown to improve the repair process. A few studies have even shown that biomaterials can induce complete regeneration through mechanisms involving immune cells. Here, we review the role of the immune system in skin repair and regeneration and describe how advances in biomaterial research may uncover immunomodulatory elements to enhance fully functional skin regeneration.