Construction Of Functionalized Two-sided Patch For Digestive And Urinary Tissue Repair

Wound repair is the eternal demand of human beings,however,wound closure is the prerequisite.Compared with invasive suture,stapler and non-invasive biological glue,tissue adhesive patch has important clinical value due to no curing process and less secondary tissue damage.Tissue adhesive patch belongs to the tablet with residual adhesion after adhesive liquid curing.Interface adhesion can instantly form after patch contacting with tissue based on physical and chemical interaction,achieving non-invasive and no-leakage tissue closure,especially on the surface of soft tissue.Due to the in vivo stubborn physiological environment,such as rich tissue fluid on the surface of tissues,frequent friction between tissues,long static contact,etc.,the redundant adhesion of the patch will adhere to other tissues,resulting in abnormal tissue adhesion,which may affect the function of other organs.The past research has not changed the hard nut by eliminating the adhesion,the essence of postoperative tissue adhesion caused by biological contamination from the surface performance of the patch,has been not solved.So far,no bioadhesive or adhesive patch preventing postoperative tissue adhesion emerged in clinic.In regard to this,it is necessary to construct a janus patch with single-sided adhesion and antifouling effect for the repair of visceral injuries.For the current problem about the hard-healing intestine,bladder and long segment of urethra,a janus patch was designed and aimed at sealing the wound without postoperative tissue adhesion or scar formation.In this study,two janus patches were prepared based on the longitudinal modification,such as the sandwiched patch of intestine closure preventing postoperative tissue adhesion,and tension-programmable non-swelling patch for bladder and urethral repair.The adhesion,antifouling performance,mechanical properties and biocompatibility were systematically evaluated in vitro and in vivo.(1)The construction of a patch toward leakage-free and anti-postoperative tissue adhesion sealing of intestinal injuriesAccording to the adhesive bonding principle,the adhesive layer,the reinforced layer and the antifouling layer were respectively optimized according to the adhesion,mechanical property and anti-adhesion effect in this study.a sandwiched patch is successfully prepared by adjusting UV-curing and preparation technology to form the stable combination between among monolayers based on physical and chemical interaction.The adhesive layer can establish fast interface adhesion based on NHS adhesive chemistry and hydrogen bonding,and the antifouling layer eliminates the surface adhesion,shielding the interference of specific protein and fibrocyte.In addition to promoting a stable and intact patch,the intermediate layer also plays a key role in energy dissipation to enhance the interface adhesion.The adhesive effect of the patch was further evaluated in the rat intestinal injury model.The results showed that the patch could rapidly and continuously adhere to the intestine,and repair intestine in two weeks.The differential pathological results showed that the patch reduced postoperative tissue adhesion by inhibiting inflammation and fibrosis pathways.Compared with the commercial Coseal and Interceed in the intestinal injury model of Bama pig,the patch for the sealing injuries caused less postoperative tissue adhesion.(2)The construction of tension programmed and non-swelling patch,and its application in the repair of the bladder and urethra.Thioctic acid,a natural anti-inflammatory small molecule transformed to supramolecule by thermal polymerization.The more stable supramolecular thioctic acid by eliminating the terminal free radicals using glycine derivant.Through spin-coating process and combination of sacrificial layer(PVA layer),a janus patch with the asymmetric adhesion in two-sided was obtained.The sacrificial layer can be dissolved in water to form a non-swelling,ultra-thin patch,which can rapidly establish interfacial adhesion through strong van der Waals force and hydrogen bonding.γ-The ferric oxide,pre-coated in supramolecular thioctic acid will slowly dissolve in acidic urine to release trivalent iron ions,forming cross-linking effect by chelating with thioctic acid.The method enhances the elastic modulus,prolongs the degradation time,improves the continuous adhesion effect,and reduces the risk of tissue infection.was constructed,and the repair effect of the patch for urinary tissue in vivo was evaluated in the of bladder and long segment urethral injury model of the rabbit.The results showed that the patch could achieve scarless repair of bladder and urethra,and avoid the problems of bladder volume reduction and urethral stricture after operation.In summary,this study constructs the two-sided patch with an asymmetric adhesion,and systematically investigated the adhesion effect,biological antifouling performance and the scarless repair in vivo and in vitro,providing a new insight for multifaceted design of the patch.