Nanocomposite Hydrogel With Hemostatic,Antibacterial And Antitumor Functions For Postoperative Wound Healing Of Melanoma

In the surgical removal of melanoma,the risk of distant metastasis will be increased when free cancer cells enter the circulatory system with blood flow.The recurrence of postoperative residual tumor also greatly reduces the cure rate.At the same time,the problem of infection in the process of defect repair becomes more and more serious because of microbial resistance.Considering the above problems,we developed a nano composite hydrogel（Gel/PF127）with excellent mechanical properties,coagulation promoting and broad-spectrum antibacterial activity.It was used to deliver paclitaxel（PTX）to the wound site after melanoma surgery,and then kill the residual tumor cells,so as to better promote wound repair.Firstly,the quaternized polyglutamic acid（Q-PGA）was obtained by linking 2,3-epoxypropyltrimethyl ammonium chloride to side chains of PGA.And then tyramine hydrochloride（Tyr）was added to the side chain of PGA and the coagulation factor Ca²⁺was introduced into the gel network.Nano composite hydrogel Gel/PF127 was successfully prepared by dynamic chemical bonding and PGA-Ca²⁺chelation.Drug loaded micelles PF127-PTX were prepared by the solvent evaporation method and loaded in the gel network.All these were aimed at achieving a hydrogel dressing with good mechanical properties and antibacterial,hemostasis and anti-tumor.The results showed that the hydrogel showed good pore structure and swelling properties.Tensile strain up to 920%and maximum breaking strength of 34 k Pa were obtained in the mechanical tests.In the cyclic loading test,the hydrogel had good mechanical stability,and the self-healing efficiency was 93.3%.In the adhesion test,the hydrogel also showed excellent adhesion effect on skin tissue,and the shear stress was 56.5 k Pa.At the same time,our study evaluated the safety,hemostatic,antibacterial and anti-tumor effects of the hydrogel in vitro.The results showed that the hydrogel exhibited good bio-safety in the cytotoxicity and hemolysis tests.The introduction of coagulation factor Ca²⁺endowed the gel with excellent coagulation effect.The quaternary ammonium gel network showed excellent growth inhibition for E.coli and S.aureus（the inhibition rate is 98%）.PF127 nano micelles could effectively load hydrophobic drug PTX and release it in the tumor environment,while the dual release system based on micelles and hydrogel could maintain long-term PTX release.After 3 days of co-culture of hydrogel and mouse melanoma cells（B16F10）,cell proliferation activity decreased significantly down to 8%.The dressing could stop bleeding quickly and prevent the free tumor cells from entering the blood circulation.The hydrogel could effectively avoid wound infection and promote wound healing.The effective delivery of PTX could induce apoptosis of tumor cells,inhibit or even kill the residual tumor,and prevent recurrence.All the results showed that the construction of in situ chemotherapy platform,which integrates trauma repair and tumor inhibition,can greatly promote the recurrence inhibition and trauma repair of melanoma.At the same time,such construction will be expected to provide a simple and efficient strategy for other cancer postoperative wound repair and tissue regeneration.