Multi-functional Hydrogel For Complex Skin Wound Repair

Hydrogel is a three-dimensional(3D)network material which is cross-linking by hydrophilic polymers.It possesses extremely high water content,tunable physicochemical and biological properties,great biocompatibility,and similarity to the extracellular matrix(ECM).These properties make hydrogels have broad application prospects in the field of life medicine,including tissue engineering scaffolds,precise drug delivery,organoid culture in vitro,high-throughput drug screening,stem cell therapy,medical wearable smart devices,etc.The hydrogel was modified from the perspectives of raw material monomer,molecular cross-linking method,micro-nano assembly structure,interface functional factor modification,etc.,so that the gel has anti-inflammatory and anti-oxidation,tissue adhesion or anti-adhesion,anti-infection,local environmental homeostasis regulation and other biological functions.By controlling the structure of the hydrogel composition,the hydrogel could play more biological functions while simulating the local microenvironment,and have better adaptability to cells,tissues and individuals.Based on this,we chose the skin as the soft tissue injury model system,and took the common problems existing for the design of hydrogels in clinical dressing.We conducted a preliminary study on its therapeutic effect and prepared a functional gel dressing to meet clinical needs.The specific contents are as follows:In the second chapter,we synthesized an assembled hydrogel microsphere porous scaffold for loading adipose-derived stem cells(ADSCs).The synthesized porous hydrogel scaffold had high cell loading efficiency and could maintain the good viability of the loaded ADSCs for a long time.We first synthesized thiolated gelatin and norbornene-based hyaluronic acid,using click chemistry as the gel formation mechanism,and processed them into hydrogel microspheres with controllable size and uniform particle size through microfluidic droplet technology.The synthesized microspheres had the shear thinning property and could be extruded with a 29 G needle,which had better filling capacity for the defect tissue and had no tissue compression or cavity structure.The porous scaffold was prepared by secondary light-induced assembly,which ensured the stable distribution of the assembled gel pores,and maintained efficient tissue circulation permeability by utilizing the porous structure,so that the ADSCs had good cell viability.The porous scaffolds loaded with ADSCs were used in skin injury repair.The cytokines secreted by the loaded ADSCs could promote neovascularization,deposition of collagen,the recovery of skin accessory tissues,and reduce scars,which has good repair effect on skin defects and burns.In the third chapter,we had synthesized a dual-network bio-functional hydrogel with multiple functions such as anti-infection,haemostasis,low swelling rate and high tissue adhesion.We synthesized catechol-modified chitosan and aldehyde dextran,and doped with magnesium oxide nanoparticles(Mg O),the Schiff base and Mg O-catechol double bond as the gel-forming mechanism were used to prepare a dual-network injectable self-healing hydrogel(CCOD-Mg O).Compared with the traditional catechol complexation formula,the complexation of Mg O and catechol had better biosafety and faster complexation rate.At the same time,the formation of the double network structure could significantly shorten the gelation time,improve the mechanical strength.The CCOD-Mg O had excellent tissue adhesion and hemostatic effect,the long-term adhesion reached to an amazing 35 k Pa,and the bleeding volume of the CCOD-Mg O group under the mouse liver hemorrhage model was only 19±3 mg,showing excellent hemostatic effect.With the help of catechol,amino groups and Mg O,CCOD-Mg O could effectively inhibit the growth of Staphylococcus aureus(S.aureus)and Escherichia coli(E.coli).The CCOD-Mg O dressing had a good auxiliary effect in the whole process of skin repair,and could significantly promote the regeneration repair of full-thickness skin defects and deep second degree skin burns.In the fourth chapter,we had proposed a local dual-gas molecular(CO and NO)gradient release hydrogel for the blood supply requirements of skin flap transplantation,which could improve the microcirculation of the transplanted tissue transplantation repair.We took the catechol-modified chitosan and aldehyde dextran prepared as the main structure,and nano-gelatin spheres carrying 4-dimethylaminopyridine were loaded into the gel.Thus,a bio-multifunctional hydrogel(DCDM)for programmatic co-delivery medicine that can deliver a dual gradient of gas molecules in a timely manner during surgery was developed.Using DCDM,the two gas molecules could be gradually released in a localized manner.The initial burst release of CO was within 1 h,which reduced early ischemia-reperfusion injury(IRI)of the transplanted tissue,and promoted vascular patency,thereby avoiding the adverse effects of inhibited blood flow patency caused by excessive NO concentration.DCDM can locally release NO gas molecules at low dose and avoid heart load increase and other systemic toxic side effects caused by systemic administration.Using rat free flap transplantation and vascular anastomosis models as research subjects,we evaluated and verified the ability of DCDM.Survival areas of the flaps in the DCDM group was33.50% higher than those in the control group.We tested the relaxation capacity of external jugular veins in vitro,and found that a single-dose administration of DCDM was sufficient to maintain the vasodilation effect for over 7 d.Based on the m RNA transcriptome sequencing(RNA?seq)and bioinformatics analysis result,DCDM increased the survival rate and promoted functional recovery of free flaps,mainly by reducing endothelial inflammatory storm and promoting neovascularization.It provides a new strategy for improving the survival rate of skin flaps and even other organ transplants.