Rational Design of Immunomodulatory Hydrogels for Chronic Wound Healing

Abstract

With all the advances in tissue engineering for construction of fully functional skin tissue, complete regeneration of chronic wounds is still challenging. Since immune reaction to the tissue damage is critical in regulating both the quality and duration of chronic wound healing cascade, strategies to modulate the immune system are of importance. Generally, in response to an injury, macrophages switch from pro‐inflammatory to an anti‐inflammatory phenotype. Therefore, controlling macrophages’ polarization has become an appealing approach in regenerative medicine. Recently, hydrogels‐based constructs, incorporated with various cellular and molecular signals, have been developed and utilized to adjust immune cell functions in various stages of wound healing. Here, the current state of knowledge on immune cell functions during skin tissue regeneration is first discussed. Recent advanced technologies used to design immunomodulatory hydrogels for controlling macrophages’ polarization are then summarized. Rational design of hydrogels for providing controlled immune stimulation via hydrogel chemistry and surface modification, as well as incorporation of cell and molecules, are also dicussed. In addition, the effects of hydrogels’ properties on immunogenic features and the wound healing process are summarized. Finally, future directions and upcoming research strategies to control immune responses during chronic wound healing are highlighted.

Self‐Assembling Peptide‐Based Hydrogels for Wound Tissue Repair

“…[ 23 ] The use of hydrogel formulations can achieve wound healing with spatiotemporal control and is thus considered an effective strategy. [ 24 ] Therefore, a series of hydrogel dressings have been developed for treating wounds.…”

“…More importantly, since wound healing is mediated by various immune cells and signaling molecules, [ 117 ] the inflammation‐related immune response has become an important topic of study. [ 24b ]…”

“…Advanced materials that interact with the immune system in a spatiotemporally controlled manner are receiving increasing attention, [ 24 , 147 ] and regulating the immune system is also conducive to the healing of chronic wounds. [ 148 ] Recently, several studies have reported hydrogel dressings with immunomodulation functions in wounds.…”

Skin Wound Healing: Normal Macrophage Function and Macrophage Dysfunction in Diabetic Wounds

“…It is unclear exactly what control of wound inflammation might look like. It could be by the use of biomaterial dressings that might modulate the immune system or through the modulation of the skin's own host defence peptides to clear an infection and alter the inflammatory phase [65][66][67][68][69]. It might be as simple as reducing the number of monocytes/macrophages entering the wound by repurposing of drugs, for example the use of anti-integrin antibodies to reduce the macrophage load [70].…”

Rational Design and Preparation of Functional Hydrogels for Skin Wound Healing

“…The wound healing process is also severely affected by the failure of macrophage response, during which persistently high levels of pro-inflammatory chemokines and large amounts of ROS are presented at the wound site ( Kharaziha et al, 2021 ). The main idea of preparing anti-inflammatory hydrogels is to give them the ability to promote macrophage polarization, eliminate ROS, reduce pro-inflammatory chemokines, and improve inflammatory inhibitory factors.…”