Applications of biomaterials for immunosuppression in tissue repair and regeneration.

The immune system plays an essential role in tissue repair and regeneration. Regardless of innate or adaptive immune responses, immunosuppressive strategies such as macrophage polarization and regulatory T (Treg) cell induction can be used to modulate the immune system to promote tissue repair and regeneration. Biomaterials can improve the production of anti-inflammatory macrophages and Treg cells by providing physiochemical cues or delivering therapeutics such as cytokines, small molecules, microRNA, growth factors, or stem cells in the damaged tissues. Herein, we present an overview of immunosuppressive modulation by biomaterials in tissue regeneration and highlight the mechanisms of macrophage polarization and Treg cell induction. Overall, we foresee that future biomaterials for regenerative strategies will entail more interactions between biomaterials and the immune cells, and more mechanisms of immunosuppression related to T cell subsets remain to be discovered and applied to develop novel biomaterials for tissue repair and regeneration. STATEMENT OF SIGNIFICANCE: Immunosuppression plays a key role in tissue repair and regeneration, and biomaterials can interact with the immune system through their biological properties and by providing physiochemical cues. Here, we summarize the studies on biomaterials that have been used for immunosuppression to facilitate tissue regeneration. In the first part of this review, we demonstrate the crucial role of macrophage polarization and induction of T regulatory (Treg) cells in immunosuppression. In the second part, distinct approaches used by biomaterials to induce immunosuppression are introduced, which show excellent performance in terms of promoting tissue regeneration.