Preparation And Application Of Wet Surface Adhesives Based On Chitosan And Polyethylene Glycol

Hydrogel is an important wet material.Due to the biomimetic properties,hydrogel have a wide range of applications in the fields of tissue engineering and biomedicine.In different applications,it is often necessary to bond hydrogels with different compositions or shapes,or to bond hydrogels with human tissues.However,the adhesives that can be used for bonding wet material are very limited,and most of them have the defects such as deterioration in water,high toxicity,low bonding strength and slow curing speed,which are difficult to meet the above application requirements.Therefore,this article intends to prepare or select suitable compounds as adhesives,and comprehensively evaluate its application feasibility for hydrogel bonding in terms of bonding strength,bonding speed and tissue compatibility.Firstly,methacrylonylated chitosan(CS-MA)was synthesized from chitosan with molecular weight of 30 kDa,and selected polyethylene glycol diacrylate(PEG-DA)with a molecular weight of 600 Da.The two compounds were prepared into hydrogel adhesives.Subsequently,the adhesion properties of the two adhesives to five representative hydrogels were evaluated.The T-peel test showed that the adhesive strength of the two adhesives increased with the increase of the mechanical strength of the hydrogel itself.The maximum peel strength of the two kinds of polyacrylamide(PAAm)/alginate double network hydrogels reached 746.67 and 333.34 N/m,indicating that all the adhesives achieved high strength adhesion.The double network hydrogels bonded by the two adhesives were subjected to autoclaving sterilization,the peel strength did not decrease significantly,indicating that the bonding stability is better.In addition,this article also traced the penetration of CS-MA into the hydrogel by fluorescent labeling,and observed the morphology of the bonding interface by scanning electron microscopy,thereby explaining that the bonding mechanism is penetration and molecular topology.Finally,the cytocompatibility of the two adhesives was evaluated,and it was found that they were not toxic to human umbilical vein endothelial cells(HUVEC).Because CS-MA adhesive has the advantages of high adhesion strength,no influence on the hardness of hydrogel and can withstand autoclaving sterilization,it is used in the construction of vascular chip.The chip is made of acrylated Pluronic F-127(F127-DA)/methacryloyl gelatin(Gel-MA)copolymer hydrogel with hardness of 11,29 and 66 kPa to simulate normal Arteries(hardness 10～30 kPa)and hardened arteries(hardness>30 kPa);the channels of the chip have 5 different widths to generate gradient fluid shear forces.The accuracy of the chip channels can reach about 20μm and it can withstand the perfusion shear force of up to 30 dyne/cm2 for a long time,so it can meet the application requirements of the vascular chip.After HUVEC were seeded on the chip and perfused culture,it was found that the cells were more extensible in the high hardness(70 kPa)hydrogel channels,while the shear force(5-26.7 dyne/cm2)had little effect on the cell morphology,which shows that in the occurrence and development of arteriosclerosis,the effect of changes in blood vessel stiffness may be greater than changes in blood shear force.Therefore,this study provides a new vascular chip model.In addition,because the small molecule PEG-DA adhesive has the advantages of fast penetration speed and fast light-initiated curing,this article prepared F127-DA hydrogel tissue patch with built-in PEG-DA adhesive.For efficient and fast photoinitiated adhesives,the minimum addition amount and the shortest initiation time of the four photoinitiators(Lithium phenyl-2,4,6-trimethylbenzoylphosphinate(LAP),2,2’-Azobis(2-methyl-N-(2-hydroxyethyl)-propionamide)(VA-086),water-soluble eosin(Eosin Y)and Ethyl phenyl(2,4,6-trimethylbenzoyl)phosphinate(TPO-L))were investigated.The results found that LAP had the fastest initiation speed,0.1%(w/v)of LAP can make the adhesive cure quickly after 395 nm LED flashlight irradiated for 5 s,and its cytotoxicity is low.Therefore,this article chose LAP as the light initiation.Subsequently,the peel strength between the hydrogel patch and the six tissues was evaluated separately,and it was found that it increased with the increase of the adhesive concentration,and reached the maximum adhesive strength after 30 s of illumination.The average peel strengths of heart,liver,kidney and stomach were 85.33,56.40,75.56,70.22,66.67 and 36.89 N/m,respectively.Then,the sealing effect of hydrogel patch on perforated organs was further evaluated,and it was found that it could effectively repair perforation of lung,heart and liver.Finally,the pig skin model was used to evaluate the histocompatibility of the hydrogel patch.It was found that the patch had no obvious damage to the skin tissue.In summary,this article prepared CS-MA adhesive and constructed a vascular chip by hydrogel bonding,which provided new ideas and new tools for the construction of complex organ chips.This article also prepared a hydrogel tissue patch with built-in PEG-DA adhesive,which is expected to be used for tissue repair and wound hemostasis.Therefore,the above-mentioned two adhesives help to expand the use of hydrogels and make them have broader application prospects in tissue engineering and other fields.