Short Peptide-polyphenol Supramolecular Water-based Adhesive

Medical adhesives play a vital role in wound closure surgical operations.Medical adhesives can replace sutures,simplify surgical operations,shorten wound recovery time and improve patient care quality.At present,the reported adhesives such as polycyanoacrylate have strong bonding ability and fast adhesion.During operation,however,it will release a large amount of heat,causing secondary damage to the wound.Moreover,they are difficult to degrade and have poor biocompatibility.Although the fibrin adhesives used clinically have good biocompatibility,they have poor bonding ability and can only be used as auxiliary materials for surgical sutures,which limits their scope of application.At present,the research focus of medical adhesives is to design and develop underwater adhesive systems with strong adhesion and good biocompatibility.In this paper,low-cost,easy-to-obtain,and biocompatible amino acids and short peptide small molecules are selected as the building blocks,and polyphenols with multiple action sites are used as the multivalent cross-linkers.A new kind of green and environmentally friendly supramolecular water-based adhesives was prepared through a one-step aqueous co-assembly.We have studied in detail their preparation conditions,formation mechanism,underwater bonding properties,and explored the bioapplication of this type of adhesive as sealant and hemostatic.First,we use basic amino acids as building blocks and tannic acid as cross-linker.Tannic acid had been widely used as a multivalent cross-linker because of its multiple sites of action(including multiple phenolic hydroxyl groups and multiple aromatic rings).After mixing the tannic acid and the basic amino acids in aqueous solution(pH～6),water-immiscible adhevise with three-dimensional network structure could be obtained with 5 mins.The shear strength tests showed that the adhesive exhibited excellent adhesion properties both in air and under water line.The rheological tests revealed that the adhesive exhibited good viscoelasticity.The FT-IR spectrum showed the presence of hydrogen bond between the basic amino acids and tannic acid.XPS spectra showed that amino acids adopt a zwitterionic form,and the phenolic hydroxyl groups of the tannic acid are in a deprotonated state at pH 6.Control experiments revealed that the side chains of the amino acids played a significant role in the formation of underwater adhesives because the cross-linked copolymerization was failed when mixing tannic acids with other amino acids,such as serine,cysteine,valine and isoleucine etc.therefore,it was speculated that the electrostatic interaction between the basic amino acids and tannic acids provided the main contribution to the formation of underwater adhesives.Remarkably,the dried adhesive can absorb water again to re-form an adhesive sample,indicating that the adhesive is reusable.The as-prepared adhesives could be placed in a syringe and be injected processability.The adhesive has the capability to resist different organic solvents.Cytotoxicity experiments,live and dead cell staining experiments and flow cytometor writed under water line by squeezing the piston of the syringe,indicative of good ry experiments showed that the adhesive has good biocompatibility.The mouse liver hemostasis model showed that the adhesive can quickly adhere and stop bleeding.This work open up a new avenue to develop medical adhesive materials.Inspite of the successful example,the prepared amino acid-tannic acid adhesives have poor cohesion,low mechanical strength,and poor adhesion.To optimize the above performance,we herein select short peptide segments as building blocks.Short peptides have the advantages of flexible design,diverse types,easy synthesis,chemical modification of functional groups,and good biocompatibility.Since the above work have demonstrated that tannic acid have stronger interaction with basic amino acids,we therefore design and synthesized several short peptides carrying basic amino acid residues as the main site of action,and introduced hydrophobic amino acid residues appropriately to improve the cohesion of supramolecular adhesives.In addition to the type of amino acid residues,the crosslink density between short peptides and polyphenols is another factor to affect the interfacial spreading,bonding and bulk mechanical strength of supramolecular adhesives.Therefore,the numbers of action sites and/or positions of short peptides and polyphenol have been considered to optimize their underwater adhesion behavior.Along this line,we designed a multi-component underwater adhesive to balance the contradictory relationship between interfacial adhesion and bulk cohesion by controlling the molar ratio between different short peptides and polyphenols.In summary,this thesis reports a new kind of water-based adhesives prepared from the aqueous co-assembly between polyphenols and small biomolecules,such as amino acids and short peptides.The preparation of the water-based adhesives is simple,green and environmentally friendly.The knowledge obtained from this study may provide new insight in the design and development of medical adhesives with biocompatibility and degradability.