Advanced Biomaterials for Regulating Polarization of Macrophages in Wound Healing

Abstract

Macrophage immunotherapy is an emerging treatment strategy that modulates the immune system to promote wound healing. The functionality and regeneration of tissue depend on spatially and temporally regulating the biophysical and biochemical microenvironmental with poorly understood mechanisms. Biomaterials are carefully crafted to display and deliver macrophage regulatory signals in a precise and near‐physiological way, serving as powerful artificial microenvironments in which to explore and direct the fate of macrophages. The review starts with discussing the classification and function of macrophages, and then introduces the polarization of macrophages in different microenvironments of conventional wounds and chronic wounds. Recent advances in biomaterials that balance the phenotypes of macrophages in wound healing are emphasized. Finally, looking ahead, the potential ability of biomaterial scaffolds to modulate immune signaling to produce an environment conducive to regeneration is discussed.

Carboxymethyl Chitosan/Tannic Acid Hydrogel with Antibacterial, Hemostasis, and Antioxidant Properties Promoting Skin Wound Repair

“…To further evaluate the anti-inflammatory ability of hydrogels, the expression of M2 macrophages in the wound region was examined using CD206 immunofluorescent labeling. − On days 3 and 7, compared to the control group, the CMC-TA hydrogel-treated group showed a greater expression level of CD206-positive M2 macrophages, as shown in Figure S4, which proved that CMC-TA hydrogels could suppress the inflammatory state of the wound. It might be because the CMC-TA had antibacterial and ROS-scavenging abilities. − These results suggested that the CMC-TA-2 hydrogel could relieve inflammation and facilitate epidermis regeneration and collagen deposition during full-thickness skin wound healing.…”

Extracellular vesicles as bioactive nanotherapeutics: An emerging paradigm for regenerative medicine

“…Cutaneous wound healing is a highly programmed process generally involving four steps: hemostasis, inflammation, proliferation, and remodeling phases 192 . During this process, macrophages play an important role in wound healing where the pro-inflammatory M1-type macrophages can induce constant inflammation and tissue degradation as well as inhibit cell proliferation and wound closure while the anti-inflammatory M2-type macrophages can effectively boost fibroblast migration, angiogenesis, and tissue repair 193 . In this regard, EVs secreted from macrophages or stem cells can be used to facilitate wound healing and skin tissue regeneration by regulating immune responses, polarizing macrophages from M1 to M2, and promoting the proliferation of skin cells and angiogenesis.…”

Recent advances in nanomedicines for regulation of macrophages in wound healing

“…Function and phenotype of macrophages can be modulated through their interactions with the chemical groups on the surface of implanted biomaterials and changing of the surface wettability [ 83 , 92 , 106 ]. For example, Bygd et al [ 107 ] prepared poly( N -isopropylacrylamide-co-acrylic acid) nanoparticles with the average size of 600 nm and modified with various functional groups.…”

“…Inorganic nanomaterials have been used to regulate macrophage polarization because inorganic materials (e.g. metal ions) are able to improve inflammatory microenvironment and wound recovery [ 106 ]. Dong et al studied the mechanism of bioactive glass (BG) enhancing wound healing via macrophage regulation [ 116 ].…”