Construction Of Mechanical Adaptable Bioadhesives And Their Application On Wound Sealing

Wound repair is the sustainable demand of human beings.Moreover,the prerequisite of wound repair is the closure of the wound site and the fixation of damaged tissue.Bioadhesive shows advantages in more convenient operation,less secondary tissue damage and wider wound adaptability ect.than the other wound repair methods such as suture,stapler and patch ect.,which was thought to be an ideal wound repair method.Bioadhesive achieves wound closure or tissue fixation by two steps.The first step is to adhere to the interface of the injured tissue in liquid form(adhesive);subsequently,it solidifies under the external stimulation and forms binding with target tissue(cohesive).Therefore,achieving perfect adaptation in mechanical properties of the adhesive to different tissues after the establishment of interfacial adhesive,which is expected to reduce the inflammatory reaction and stress concentration caused by the difference in mechanical properties between materials and tissues,is considered to be the ideal form of cohesive.However,humans' tissues are in so many kinds and show great differences in mechanical properties(their elastic moduli across six orders from k Pa to GPa level).Unfortunately,there were no products or researches of bioadhesive with tunable mechanical properties that were suitable for different soft tissues and hard tissues.In view of this,the main purpose of this study is to construct an adhesive with adjustable mechanical properties so that it can adapt with different soft tissues and hard tissues in mechanical properties.Furthermore,this kind of adhesive was expected to be utilized for the treatment of vary kinds of injured tissues.Herein,we constructed a kind of bioadhesive with tunable elastic modulus from k Pa to GPa level and explored the possibility of their mechanical adaptation to varies tissues.Furthermore,this kind of bioadhesive was utilized to several representative tissues and their effectiveness in wound closure and tissue repair were systematically evaluated.(1)Construction of bioadhesive with mechanical adaptability to multi-tissuesPolyurethane with tunable mechanical properties was chose as the candidate of bioadhesive.In this work,we constructed a kind of two-component polyurethane adhesive with controllable mechanical properties and rapid curing capability by the synthesis of different polyurethane prepolymers and the development of new curing agents.(1)Aliphatic and aromatic polyurethane prepolymers with different chain lengths and crosslinking degrees were synthesized,as well as secondary amine ester curing agents with different chain rigidity were developed.As a result,the curing time of polyurethane bioadhesives can be controlled from tens of seconds to several minutes.(2)By the combination of different polyurethane prepolymers with different secondary amine esters,the elastic moduli of the adhesives could be adjusted from 8.1 k Pa to 0.66 GPa,which were mechanically adapted with most of the soft tissues and hard tissues.In addition,their thermodynamics,swelling behaviors and microstructure after gelation were also evaluated.These two-component polyurethane adhesives showed minimal cytotoxicity,so they could be further used for the bonding of tissues.(2)Application of mechanical adaptive adhesive in different tissuesThis kind of polyurethane bioadhesives were then used for gluing four common tissues:lung,intestine,skin and bone.Their adhesive properties to tissues were systematically evaluated from the aspects of adhesion strength,wet-environment adhesion performances,adhesion fatigue performances and the adhesion interface in vitro comparison with commercial adhesives.The results indicated that,polyurethane adhesives with mechanical adaptability to tissue showed higher adhesive strength and adhesive energy than that of commercial PEG-based adhesive in sealing pulmonary leakage,better sealing effect in intestinal leakage than that of suture,and better flexibility than commercial ?-cyanoacrylate medical adhesive,and higher bonding strength than commercial bone cement(PMMA).What's more,this kind of mechanical adaptive adhesives showed good adhesion fatigue performances when used for bonding different tissues,which were of great significance for biological tissues that continuously must operate in complex mechanical environment.In vivo study showed that the mechanical adaptive polyurethane adhesives could achieve continuous and reliable closure of Bama pig lung air leakage wound and avoid "pneumothorax",and achieved effective plugging in a full penetration of Bama pig intestinal leakage and avoided postoperative adhesion.The results also showed that the polyurethane adhesives could seal a full-thickness back skin wound of Bama pig with accelerated wound healing effect,and achieved the fixtion of segmental defect of goat thigh tibia and the recovery of sports ability of goat with twice success rate than that of commercial bone cement.Generally speaking,by the construction of a kind of polyurethan bioadhesives with mechanical adaptability to tissues and then revealed their adhesion mechanism from the perspective of adhesion strength and adhesion fatigue etc.,we believe that this work will be very helpful for the development of wound repair materials that can be used in different tissues and organs.