Immunomodulatory hydrogels for skin wound healing: cellular targets and design strategy

Skin wounds significantly impact the global health care system and represent a significant burden on the economy and society due to their complicated dynamic healing processes, wherein a series of immune events are required to coordinate normal and sequential healing phases, involving multiple immunoregulatory cells such as neutrophils, macrophages, keratinocytes, and fibroblasts, since dysfunction of these cells may impede skin wound healing presenting persisting inflammation, impaired vascularization, and excessive collagen deposition. Therefore, cellular target-based immunomodulation is promising to promote wound healing as cells are the smallest unit of life in immune response. Recently, immunomodulatory hydrogels have become an attractive avenue to promote skin wound healing. However, a detailed and comprehensive review of cellular targets and related hydrogel design strategies remains lacking. In this review, the roles of the main immunoregulatory cells participating in skin wound healing are first discussed, and then we highlight the cellular targets and state-of-the-art design strategies for immunomodulatory hydrogels based on immunoregulatory cells that cover defect, infected, diabetic, burn and tumor wounds and related scar healing. Finally, we discuss the barriers that need to be addressed and future prospects to boost the development and prosperity of immunomodulatory hydrogels. Schematic illustration of roles and targets of immunoregulatory cells and hydrogel design strategies to promote wound healing.