Bifunctional Cx43 Mimic Peptide Grafted Hyaluronic Acid Hydrogels Inhibited Tumor Recurrence and Stimulated Wound Healing for Postsurgical Tumor Treatment

Tumor recurrence and delayed wound healing after tumor excision pose great threats to patients. Bifunctional composite biomaterials prepared by simply mixing one component for inhibiting tumor recurrence and another component for enhancing wound healing usually ignores the physico-chemical property integration of the two components. In this study, a bifunctional Cx43 mimic peptide, juxtamembrane 2 (JM2), is synthesized and grafted to hyaluronic acid (HA) to generate a homogeneous bifunctional injectable hydrogel system (HA-JM2) for simultaneously inhibiting tumor recurrence and enhancing wound healing. Results demonstrate that JM2 can inhibit proliferation and induce apoptosis of tumor cells in vitro, thereby effectively inhibiting tumor growth in vivo. In addition, JM2 can recruit repairing cells into the wound site and control the ATP release from these cells, which creates a favorable inflammatory microenvironment for tissue regeneration. As the HA-JM2 hydrogel can sustainably release JM2 to control host inflammation responses and stimulate angiogenesis, it can accelerate the wound healing in full-thickness skin defects. When the HA-JM2 hydrogel is applied to incompletely excisional tumor defects, it simultaneously shows inhibitory effects on tumor recurrence and stimulatory effects on skin wound healing. Taken together, the bifunctional HA-JM2 injectable hydrogel has great application potential for postsurgical tumor treatment.