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A“T.E.S.T.”hydrogel bioadhesive assisted by corneal cross-linking for in situ sutureless corneal repair

Bioactive Materials 2023年第7期25卷 333-346页

作者： Meiyan Li Ruoyan Wei Chang Liu Haowei Fang Weiming Yang Yunzhe Wang Yiyong Xian Kunxi Zhang Yong He Xingtao Zhou Department of Ophthalmology EYE&ENT Hospital of Fudan University ShanghaiChina NHC Key Laboratory of Myopia(Fudan University) ShanghaiChina State Key Laboratory of Fluid Power and Mechatronic Systems School of Mechanical EngineeringZhejiang UniversityHangzhouChina Shanghai Research Center of Ophthalmology and Optometry ShanghaiChina Department of Ophthalmology Children’s Hospital of Fudan UniversityNational Children’s Medical CenterShanghaiChina Department of Polymer Materials School of Materials Science and EngineeringShanghai UniversityShanghaiChina

Corneal transplantation is an effective clinical treatment for corneal diseases,which,however,is limited by donor corneas.It is of great clinical value to develop bioadhesive corneal patches with functions of“Transparency”and“Epithelium&Stroma generation”,as well as“Suturelessness”and“Toughness”.To simultaneously meet the“T.E.S.T.”requirements,a light-curable hydrogel is designed based on methacryloylated gelatin(GelMA),Pluronic F127 diacrylate(F127DA)&Aldehyded Pluronic F127(AF127)co-assembled bi-functional micelles and collagen type I(COL I),combined with clinically applied corneal cross-linking(CXL)technology for repairing damaged cornea.The patch formed after 5 min of ultraviolet irradiation possesses transparent,highly tough,and strongly bio-adhesive performance.Multiple cross-linking makes the patch withstand deformation near 600%and exhibit a burst pressure larger than 400 mmHg,significantly higher than normal intraocular pressure(10-21 mmHg).Besides,the slower degradation than GelMA-F127DA&AF127 hydrogel without COL I makes hydrogel patch stable on stromal beds in vivo,supporting the regrowth of corneal epithelium and stroma.The hydrogel patch can replace deep corneal stromal defects and well bio-integrate into the corneal tissue in rabbit models within 4 weeks,showing great potential in surgeries for keratoconus and other corneal diseases by combining with CXL.

关键词： Tough hydrogel bioadhesives Corneal patch CXL Sutureless repair

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A sandwiched patch toward leakage-free and anti-postoperative tissue adhesion sealing of intestinal injuries

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Bioactive Materials 2023年第6期24卷 112-123页

作者： Wei Yang Chengkai Xuan Xuemin Liu Qiang Zhang Kai Wu Liming Bian Xuetao Shi National Engineering Research Centre for Tissue Restoration and Reconstruction South China University of TechnologyGuangzhou510006China School of Materials Science and Engineering South China University of TechnologyGuangzhou510640China Key Laboratory of Biomedical Engineering of Guangdong Province South China University of TechnologyGuangzhou510006China Key Laboratory of Biomedical Materials and Engineering of the Ministry of Education South China University of TechnologyGuangzhou510006China School of Biomedical Sciences and Engineering South China University of TechnologyGuangzhou International CampusGuangzhou511442China Guangzhou Soonheal Medical Technology.Co LtdGuangzhou510230China

Ideal repair of intestinal injury requires a combination of leakage-free sealing and postoperative antiadhesion.However,neither conventional hand-sewn closures nor existing bioglues/patches can achieve such a combination.To this end,we develop a sandwiched patch composed of an inner adhesive and an outer antiadhesive layer that are topologically linked together through a reinforced interlayer.The inner adhesive layer tightly and instantly adheres to the wound sites via-NHS chemistry;the outer antiadhesive layer can inhibit cell and protein fouling based on the zwitterion structure;and the interlayer enhances the bulk resilience of the patch under excessive deformation.This complementary trilayer patch(TLP)possesses a unique combination of instant wet adhesion,high mechanical strength,and biological inertness.Both rat and pig models demonstrate that the sandwiched TLP can effectively seal intestinal injuries and inhibit undesired postoperative tissue adhesion.The study provides valuable insight into the design of multifunctional bioadhesives to enhance the treatment efficacy of intestinal injuries.

关键词： Trilayer patch bioadhesives Preventing postoperative adhesion Antiadhesion Intestinal injuries

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In situ Injectable Tetra-PEG Hydrogel Bioadhesive for Sutureless Repair of Gastrointestinal Perforation

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Chinese Journal of Chemistry 2023年第23期41卷 3339-3348页

作者： Shurong Li Yiwen Xian Gang He Luyuan Chen Zhihui Chen Yonglong Hong Chong Zhang Decheng Wu Guangdong Provincial Key Laboratory of Advanced Biomaterials Department of Biomedical EngineeringSouthern University of Science and TechnologyNo.1088 Xueyuan AvenueNanshan DistrictShenzhenGuangdong518055 China These authors contribute equally. Stomatology Center Shenzhen HospitalSouthern Medical UniversityNo.1333 New RoadBaoan DistrictShenzhenGuangdong518101 China

Hydrogel bioadhesives represent promising and efficient alternatives to sutures or staples for gastrointestinal(GI)perforation management.However,several concerns remain for the existing bioadhesives including slow and/or weak adhesive,poor mechanical strength,low biocompatibility,and poor biodegradability,which largely limit their clinical application in GI perforation repair.In this work,we introduce an in situ injectable Tetra-PEG hydrogel bioadhesive(SS)composed of tetra-armed poly(ethylene glycol)amine(Tetra-PEG-NH2)and tetra-armed poly(ethylene glycol)succinimidyl succinate(Tetra-PEG-SS)for the sutureless repair of GI defects.The SS hydrogel exhibits rapid gelation behavior and high burst pressure and is capable of providing instant robust adhesion and fluid-tight sealing in the ex vivo porcine intestinal and gastric models.Importantly,the succinyl ester linkers in the SS hydrogel endow the bioadhesive with suitable in vivo degradability to match the new GI tissue formation.The in vivo evaluation in the rat GI injured model further demonstrates the successful sutureless sealing and repair of the intestine and stomach by the SS hydrogel with the advantages of neglectable postsurgical adhesion,suppressed inflammation,and enhanced angiogenesis.Together,our results support potential clinical applications of the SS bioadhesive for the high-efficient repair of GI perforation.

关键词： Gastrointestinal perforation bioadhesives Gels Biological activity Sutureless repair Regenerative wound healing

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Bridging wounds:tissue adhesives’essential mechanisms,synthesis and characterization,bioinspired adhesives and future perspectives

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Burns & Trauma 2022年第1期10卷 216-245页

作者： Kaige Xu Xiaozhuo Wu Xingying Zhang Malcolm Xing Department of Mechanical Engineering University of ManitobaWinnipegManitoba R3T 2N2Canada

bioadhesives act as a bridge in wound closure by forming an effective interface to protect against liquid and gas leakage and aid the stoppage of bleeding.To their credit,tissue adhesives have made an indelible impact on almost all wound-related surgeries.Their unique properties include minimal damage to tissues,low chance of infection,ease of use and short wound-closure time.In contrast,classic closures,like suturing and stapling,exhibit potential additional complications with long operation times and undesirable inflammatory responses.Although tremendous progress has been made in the development of tissue adhesives,they are not yet ideal.Therefore,highlighting and summarizing existing adhesive designs and synthesis,and comparing the different products will contribute to future development.This review first provides a summary of current commercial traditional tissue adhesives.Then,based on adhesion interaction mechanisms,the tissue adhesives are categorized into three main types:adhesive patches that bind molecularly with tissue,tissuestitching adhesives based on pre-polymer or precursor solutions,and bioinspired or biomimetic tissue adhesives.Their specific adhesion mechanisms,properties and related applications are discussed.The adhesion mechanisms of commercial traditional adhesives as well as their limitations and shortcomings are also reviewed.Finally,we also discuss the future perspectives of tissue adhesives.

关键词： Adhesive patch Adhesion mechanism Nature-inspired Tissue adhesives bioadhesives

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