A Catechol Bioadhesive For Rapid Hemostasis And Healing Of Traumatic Internal Organs And Major Arteries

Purpose:Uncontrolled hemorrhage caused by trauma to internal organs or major arteries poses critical threats to lives.However,rapid hemostasis followed by tissue repair remains an intractable challenge in surgery owing to the lack of ideal internal-use adhesives that can achieve fast and robust wet adhesion and accelerate wound healing.Herein,we develop a robust hemostatic bioadhesive（CAGA）from novel highly-branched aminoethyl gelatin with end-grafted abundant catechol（Gel-AE-Ca）.The unique chemical structure of Gel-AE-Ca makes CAGA capable of gelling on wet tissues via synergetic cross-linking of catechol-Fe³⁺chelation and horseradish peroxidase（HRP）/H₂O₂-triggered covalent bonds using a dual-channel needle,meeting the key demands of internal medical applications（e.g.,instant and strong wet adhesion,injectability,biocompatibility,self-healing,stretching flexibility,infection resistance,and proper biodegradability）.Methods:1、Amine-based high-branched chain gelatin（Gel-AE）and gelatin-rich macromolecular bond monomer（Gel-AE-Ca）were designed and synthesized,and CAGA hemostatic adhesive was developed to meet the needs of medical use.2、NMR hydrogen spectroscopy was used to verify the chemical structures of Gel-AE and Gel-AE-Ca.3、The properties of gelformation time,in vitro stability and degradability,adhesion,plugging strength and other properties of CAGA gel were tested by in vitro test.4、The cell compatibility of CAGA gel was tested by a series of cell experiments,such as dead live cell assay,F-actin staining,cell proliferation,etc.5、The antibacterial ability of the CAGA gels was tested by bacterial experiments.6、The biocompatibility of CAGA gel in animals was tested through a series of animal experiments,such as:hemostasis test of liver and heart,and arterial anastomosis surgery.Result:Among them,CAGA exhibits rapid gelation within 10s and robust wet tissue adhesion up to 115.0±13.1 k Pa of shear strength and 245.0±33.8 mm Hg of sealing strength.In vivo trials demonstrate that CAGA can not only effectively seal anastomosis of the carotid artery,but achieve rapid hemostasis on the sites of liver incisions and penetrating cardiac wounds within 10s.The wound closure by CAGA and its timely biodegradation promote wound healing of the vital organs.Conclusion:CAGA,a bioadhesive developed by the newly developed Gel-AE-Ca precursor,by triggering the covalent bond of catechol-Fe³⁺chelation and horseradish peroxidase（HRP）/H₂O₂.CAGA would be a very promising surgical and emergency hemostasis.CAGA can achieve rapid hemostasis within 10 seconds,produce a mild inflammatory response,and aid in tissue healing and repair.CAGA is a promising tissue adhesive that can be used for the adhesion of visceral organs,achieve effective arterial or visceral hemostasis,and promote tissue repair.The new adhesive with good performance can simplify the operation process,deal with many different situations in the operation,and provide more options for first aid and surgery.