Study On The Preparation And Application Of Quaternized Chitin Antibacterial Nanofiber Wound Dressings

Background Skin injury,caused by mechanical force,heat,tumor,endocrine and iatrogenic factors,is one of the most common diseases in clinic.Wound healing is affected by some internal and external factors,and is prone to adverse outcomes,such as necrosis,delayed wound healing,scar formation,loss of pain and temperature sensation.Tissue engineering wound dressing(TEWD)is the class III medical devices.Its appearance has greatly accerelated the wound closure rate,and promoted the development of wound healing to a higher level.Antibacterial activity is the core clinical need of TEWD.TEWD should also possess some other biological activities,including promoting cell proliferation,improving blood supply,modifying inflammatory micro-environment.Perfect TEWD do not exist now.In the previous work,we adopted natural shrimp shells to chemically synthesize a cationic quaternarized salt.The obtained product named as quaternized chitin(QC)exhibited broadspectrum antibacterial activity.QC is positive charged and has amphiphilic long-chain polymer structure.By adsorbing bacteria,the hydrophobic chain is inserted into the cell membrane to induce osmotic pressure change,so as to kill bacteria.QC is not easy to develop drug resistance,and its biocompatibility,degradability and processability are relatively good.Objective To prepare a series of QC-based antibacterial nanofiber dressing,and perform the corresponding translational medicine research.Methods Two design options were available:(1)polycaprolactone(PCL)/ silk fibroin(SF)nanofibers were prepared by high voltage electrospinning,and then QC and SF were layer by layer(LBL)assembled;(2)Polylactic acid glycolic acid copolymer(PLGA)nanofibers were prepared,and QC and basic fibroblast growth factor(FGF2)-hyaluronic acid(HA)were LBL assembled.The physicochemical properties,biosafety,bio-activity and antibacterial properties of the products were evaluated by a series of experimental methods.A rat full-thickness skin injury model was contructed to explore the effect and mechanism of skin repair.Results Two nanofiber dressings were successfully prepared,and named as PQCSF and PQHF respectively.The nanofibers exhibited typical interwaved network structure.With the increase of LBL self-assembld layers,the amount of polyelectrolyte complexes gradually increased,resulting in regular changes in their mechanical strength,hydrophobicity,biocompatibility and antibacterial properties.These nanofibers were rich in QC,which had good killing effects on Gram-positive bacteria(S.aureus),Gram-negative bacteria(E.coli)and drug-resistant bacteria(MRSA).There were still some differences in the properties of the two nanofiber dressings.Compared with PQCSF,PQHF could release FGF2,and promote fibroblast proliferation and migration by accelerating cell cycle process and inducing epithelial mesenchymal transformation(EMT).PQCSF and PQHF could promote infected skin regeneration,mainly by improving the wound closure rate,reducing inflammation,inducing hair follicle regeneration,vascularization,re-epithelialization and collagen synthesis(type I collagen and type III collagen).Conclusion PQCSF and PQHF have achieved the expected performance and can better meet the clinical needs.Among them,the biological activity and mechanism of PQHF are more solid,and it has the potential to declare the class III medical device.This work has reference significance in combining multiple chemical compositions and hierarchical structures for the design of novel multifunctional composite materials.