Immune cells have emerged as powerful regulators of regenerative as well as pathological processes. The vast majority of regenerative immunoengineering efforts have focused on macrophages; however, growing evidence suggests that other cells of both the innate and adaptive immune system are as important for successful revascularization and tissue repair. Moreover, spatiotemporal regulation of immune cells and their signaling have a significant impact on the regeneration speed and the extent of functional recovery. In this review, we summarize the contribution of different types of immune cells to the healing process and discuss ways to manipulate and control immune cells in favor of vascularization and tissue regeneration. In addition to cell delivery and cell-free therapies using extracellular vesicles, we discuss in situ strategies and engineering approaches to attract specific types of immune cells and modulate their phenotypes. This field is making advances to uncover the extraordinary potential of immune cells and their secretome in the regulation of vascularization and tissue remodeling. Understanding the principles of immunoregulation will help us design advanced immunoengineering platforms to harness their power for tissue regeneration.

Department of Bioengineering University of California Los Angeles CA 90095 USA

Department of Bioengineering University of California Los Angeles CA 90095 USA; Department of Biomaterials and Tissue Engineering Institute of Physiology of the Czech Academy of Sciences Prague 14220 Czech Republic

Department of Bioengineering University of California Los Angeles CA 90095 USA; Eli and Edythe Broad Stem Cell Research Center University of California Los Angeles CA 90095 USA; Department of Medicine David Geffen School of Medicine University of California Los Angeles CA 90095 USA

Division of Cardiology Department of Internal Medicine David Geffen School of Medicine University of California Los Angeles CA 90095 USA; Eli and Edythe Broad Stem Cell Research Center University of California Los Angeles CA 90095 USA; Molecular Biology Institute University of California Los Angeles Los Angeles CA 90095 USA

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