Research On Immunomodulatory Hydrogel To Promote Skin Damage Repai

As the largest human organ,skin injuries such as burns and radiation damage seriously threaten life and health.In recent years,mechanism studies have shown that the immune system plays an important role in the healing process of skin wounds.The development of different immune regulatory treatment strategies to reshape tissue immune microenvironment and promote wound healing has become one of the focuses of biomedical research.In particular,hydrogels as scaffolds can regulate innate or adaptive immunity,showing great potential in biomedical applications such as disease treatment and mediating endogenous tissue repair.Therefore,this paper takes the construction of bioactive hydrogel materials as the starting point to study the effect of its immunomodulatory function on promoting refractory wounds such as burns and burns and radiation injuries,and carries out the following work:Firstly,carboxybetaine(PCB)and fluorinated carboxybetaine(PFCB)hydrogels were prepared by free radical co-polymerization,which not only had excellent anti-protein adsorption ability and anti-cell adhesion ability,but also had excellent cytocompatibility.In particular,the results of co-culture with macrophages showed that the two amphoteric ionic hydrogels did not affect the morphology and immune function of macrophages,including the gene expression of M1 and M2 macrophage-related markers and the secretion of inflammatory factors.After 8 weeks of implantation,the two zwitterionic hydrogels did not develop dense fibrous capsules in mice,and the expression of tumor necrosis factor(TNF-α)in the tissues surrounding the hydrogels was maintained at a low level.The above results proved that these two zwitterionic hydrogels did not have immunogenicity,which was beneficial to avoid being recognized by the immune system,and could effectively reduce the risk of inducing inflammation and adhesion to tissues.Furthermore,the zwitterionic hydrogel system was conbined with epigallocatechin gallate(EGCG)-Cu2+ organic framework microcapsules(EGCG-Cu)to obtain zwitterionic hydrogels loaded with microcapsules(EGCG-Cu@CBgel).By regulating immune metabolism and promoting neovascularization to achieve the goal of promoting scald wound repair.Among them,on the one hand,zwitterionic hydrogels with anti-adhesion properties and flexible mechanics were used as wound dressing to prevent bacterial adhesion and unnecessary secondary damage to newly formed skin tissue,and on the other hand,to release active EGCG-Cu microcapsule on the wound.The EGCG active substance released not only scavenged excess ROS and reduced oxidative stress damage in tissues,but also significantly reduced the glycolytic metabolism of Ml-type macrophages,including significantly reducing pyruvate content and the accumulation of pyruvate and increasing acetyl-CoA required for its conversion into the tricarboxylic acid cycle(TCA);as well as the accumulation of succinic acid and citric acid.ROS production and HIF-1αexpression were decreased to inhibit glycolytic metabolism,promote the restoration of normal tricarboxylic acid cycle,and reduce the proportion of pro-inflammatory M1 macrophages in tissue microenvironment.Cu2+ could promote the proliferation and migration of endothelial cells and promote neovascularization.Therefore,EGCGCu@CBgel hydrogel restructured the inflammatory microenvironment of scald tissue through immune metabolism regulation,reduced secondary damage caused by tissue oxidative stress and inflammation,promoted angiogenesis and accelerated collagen deposition to accelerate wound healing process.Based on the important role of ROS clearance in skin damage repair,we proceeded to construct injectable melanin-like oxidized tyrosine polypeptide hydrogels(PETyrO)with polyphenol hydroxyl groups and intramolecular/interconjugated structures.PETyrO hydrogel could not only increase the temperature to more than 50℃ under near-infrared light irradiation,but also played an efficient role in photothermal treatment of tumor.After 14 days of treatment,it could completely eliminate breast cancer tumor tissue.At the same time,after photothermal treatment,the widespread phenolic hydroxyl group and conjugated structure in PETyrO hydrogel could effectively scavenge excess ROS,reduce the M1-type polarization of macrophages,regulate the inflammatory microenvironment,and accelerate the damage and repair of normal tissues around the tumor caused by hyperthermia.Further,in order to effectively treat irradiated skin injury,itaconic acid(ITA)selfassembled micelles with significant anti-inflammatory activity were loaded on PETyrO hydrogel(ITA@PETyrO).The efficient ROS scavenge ability of PETyrO significantly reduced radiation damage at cell level and tissue level.The introduction of ITA endowed hydrogel excellent anti-inflammatory ability,reducing macrophage polarization to M1 type and secretion of pro-inflammatory cytokines by activating related anti-inflammatory signaling pathways,and reducing inflammatory response and secondary injury in injured tissues.Through the synergistic action of antioxidant and anti-inflammatory,it was expected to effectively promote the repair of radiation skin damage.In conclusion,immunoregulatory hydrogels were expected to reshape tissue immune microenvironment through the combination of structural design and functionalization,and played an important role in the treatment of tumor and other major diseases,as well as in biomedical applications such as promoting the repair of hard-healing wounds such as burns and radiation injuries.