title: A novel injectable tissue adhesive based on oxidized dextran and chitosan.
abstract: A surgical adhesive that can be used in different surgical situations with or without sutures is a surgeons' dream and yet none has been able to fulfill many such demanding requirements. It was therefore a major challenge to develop an adhesive biomaterial that stops bleeding and bond tissues well, which at the same time is non-toxic, biocompatible and yet biodegradable, economically viable and appealing to the surgeon in terms of the simplicity of application in complex surgical situations. With this aim, we developed an in situ setting adhesive based on biopolymers such as chitosan and dextran. Dextran was oxidized using periodate to generate aldehyde functions on the biopolymer and then reacted with chitosan hydrochloride. Gelation occurred instantaneously upon mixing these components and the resulting gel showed good tissue adhesive properties with negligible cytotoxicity and minimal swelling in phosphate buffered saline (PBS). Rheology analysis confirmed the gelation process by demonstrating storage modulus having value higher than loss modulus. Adhesive strength was in the range 200-400gf/cm2which is about 4-5 times more than that of fibrin glue at comparable setting times. The adhesive showed burst strength in the range of 400-410mm of Hg which should make the same suitable as a sealant for controlling bleeding in many surgical situations even at high blood pressure. Efficacy of the adhesive as a hemostat was demonstrated in a rabbit liver injury model. Histological features after two weeks were comparable to that of commercially available BioGlue®. The adhesive also demonstrated its efficacy as a drug delivery vehicle. The present adhesive could function without the many toxicity and biocompatibility issues associated with such products.
  
  
  
  Though there are many tissue adhesives available in market, none are free of shortcomings. The newly developed surgical adhesive is a 2-component adhesive system based on time-tested, naturally occurring polysaccharides such as chitosan and dextran which are both biocompatible and biodegradable. Simple polymer modification has been carried out on both polysaccharides so that when aqueous solutions of both are mixed, the solutions gel in less than 10s and forms an adhesive that seals a variety of incisions. The strength of the adhesive is over 5-times the strength of commercially available Fibrin glue and is more tissue compliant than BioGlue®. This adhesive biomaterial showed excellent tissue bonding, was hemostatic, biocompatible and biodegradable. The significance of this work lies on the features of the developed tissue adhesive that it stops bleeding, bond the tissues well, can act as a drug delivery vehicle and would appeal to the surgeon in terms of the simplicity of application in complex surgical situations. There is no need for special delivery systems for application of this adhesive. The two-component adhesive can be applied one over the other using syringes. There is also no need for light curing with UV or visible light and the gelation between the two components spontaneously takes place on application leading to excellent tissue bonding.
authors.affiliation: Department of Biosciences & Bioengineering, Indian Institute of Technology Bombay, Mumbai, Maharashtra 400 076, India.
authors.forename: Biji
authors.initials: B
authors.lastname: Balakrishnan
authors.affiliation: In Vivo Models and Testing Division, BMT Wing, Sree Chitra Tirunal Institute for Medical Sciences & Technology, Thiruvanthapuram, Kerala 695012, India.
authors.forename: Dawlee
authors.initials: D
authors.lastname: Soman
authors.affiliation: In Vivo Models and Testing Division, BMT Wing, Sree Chitra Tirunal Institute for Medical Sciences & Technology, Thiruvanthapuram, Kerala 695012, India.
authors.forename: Umashanker
authors.initials: U
authors.lastname: Payanam
authors.affiliation: Centre de Rechercheen Imagerie Interventionnelle (Cr2i) APHP-INRA, Bâtiment 402, Domaine de Vilvert, 78352 Jouyen Josas, Cedex, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Laurent
authors.affiliation: Centre d'Etudes Pharmaceutiques, UMR CNRS 8612, Université Paris-Sud, 5 rue J.B. Clément, 92296 Chatenay-Malabry, Cedex, France.
authors.forename: Denis
authors.initials: D
authors.lastname: Labarre
authors.affiliation: Biomaterials Laboratory, Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras, Chennai, Tamil Nadu 600 036, India. Electronic address: ajk@iitm.ac.in.
authors.forename: Athipettah
authors.initials: A
authors.lastname: Jayakrishnan
mesh_terms: D000268:Adhesiveness; D000818:Animals; D048271:Chitosan / Q000008:administration & dosage* / Q000737:chemistry*; D003911:Dextrans / Q000008:administration & dosage* / Q000737:chemistry*; D007267:Injections / Q000379:methods; D008107:Liver Diseases / Q000473:pathology / Q000628:therapy*; D008297:Male; D008422:Materials Testing; D010084:Oxidation-Reduction; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D013718:Tensile Strength; D014014:Tissue Adhesives / Q000008:administration & dosage* / Q000138:chemical synthesis*; D016896:Treatment Outcome; D014783:Viscosity
chemical_list: D003911:Dextrans; D014014:Tissue Adhesives; D048271:Chitosan
keywords: Chitosan; Dextran; Hemostat; Injectable; Tissue adhesive