Title: Immunomodulating biomaterials

Abstract

The immune system is quite related to various major diseases including cancer, cardiovascular diseases, and tissue defect. Here we propose that immunomodulating biomaterials can improve the treatment of major diseases by activating immune cells such as dendritic cells (DCs) and macrophages directly in vivo. Specially, self-assembled peptide hydrogels were prepared to deliver tumor antigens and TLR agonists. It was demonstrated that the use of hydrogels could significantly increase the uptake of antigens by DCs, thereby facilitating the maturation of DCs and antigen presentation to naive T cells, which elicited antitumor T-cell responses. In combination with immune checkpoint blockade, the immunotherapy efficiency against melanoma could be further augmented. Besides, we found that immunogenic chemotherapy by nanomedicine could induce the immunogenic death of cancer cells and the release of endogenous tumor antigens, which enhanced the recognition of cancer cells by effector T-cells, amplifying the antitumor T-cell immunity. On the other hand, bioinspired glycopeptide hydrogels were fabricated to serve as artificial extracellular matrix (ECM) for tissue repair and regeneration. It was found that in salt solution, glucomannan-Q11 peptide could self-assemble into nanofiber hydrogels with 3D network structure. Significantly, this glycopeptide hydrogel notably polarized bone marrow derived macrophage (BMDM) into M2-type through mannose receptor (MR)-induced ERK/STAT6 signaling pathway. In mice with full-thickness cutaneous defects, the injection of glycopeptide hydrogel tremendously modulated the macrophages recruited in the wound microenvironment into anti-inflammatory M2 macrophages, which greatly accelerated the wound healing. Moreover, the development of antibacterial hydrogel enabled the complete eradication of methicillin-resistant staphylococcus aureus at the wound, thus, further reducing the inflammatory level. Our works clearly demonstrated that the development of immunomodulating biomaterials plays significant role in controlling the immune response for cancer treatment and tissue regeneration. Immunomodulation represents an advanced approach for the treatment of major diseases.