Preparation And Application Of A Copper-based Nanozyme Composite Hydrogel For The Repair Of Various Refractory Wounds

Skin is the largest organ of the human body,and it is the most important natural barrier to protect internal tissues from external stimuli.When the skin is damaged,the immune and protective mechanisms of the skin are lost.Therefore,bacteria and microorganisms can easily infect the injured site,making it difficult to heal the wound;due to the metabolic imbalance around the wound caused by diabetes,insufficient angiogenesis,etc.,the wound is also difficult to heal.Antibiotics are usually used clinically to inhibit bacterial infection and treat diabetic wounds,but the problem of bacterial resistance caused by abuse of antibiotics has gradually become a greater medical threat.Bioactive nanozymes are very beneficial to the healing of chronic wounds such as infection and diabetic wounds.In this study,a structurally stable copper hydrogen phosphate nanosheets enzyme(CuP NSs)was synthesized,which has good near-infrared(NIR)photothermal conversion performance,peroxidase(POD)-like catalytic activity and sustained copper(Cu)ions release ability.In order to verify its application potential in various refractory wounds,it was compounded with sodium alginate(Alg)hydrogel with good biocompatibility to prepare Alg/CuP composite hydrogel,which showed significant wound healing ability.The Alg/CuP composite hydrogel can continuously release Cu ions at an appropriate concentration.The hydroxyl ions(·OH)produced by the catalysis and the released Cu ions have high bacterial removal efficiency for Staphylococcus aureus(S.aureus)and Escherichia coli(E.coli),respectively.In addition,when the Alg/CuP hydrogel is heated at 40°C,the Alg/CuP composite hydrogel significantly accelerates the catalytic and Cu ions release properties,which in turn improves the antibacterial properties of the Alg/CuP composite hydrogel.Moreover,in cell experiments,it was verified that the Alg/CuP hydrogel produced“ hot ions ” under 40°C,which was beneficial to the proliferation and migration of human skin fibroblasts(HDFs)and human umbilical vein endothelial cells(HUVECs),in vitro vascularization of HUVECs and related angiogenesis and heat shock protein gene(VEGF,b FGF,e NOS,HIF-1α,VCAM1,CD31,HSP90)expression.Finally,the ability of antiinfection and wound healing was verified in animal experiments.A mouse wound infection model was constructed to verify the antibacterial performance of 40°C combined with Alg/CuP composite hydrogel.A mouse diabetic wound model was constructed to verify the synergistic effect of 40°C and Alg/CuP composite hydrogel on promoting new angiogenesis,thereby promoting wound repair performance.The results show that the designed composite hydrogel makes full use of the multifunctional properties of CuP NSs nanozymes and broadens the way to design multifunctional dressings for refractory wounds in different clinical scenarios.