title: Structuring of composite hydrogel bioadhesives and its effect on properties and bonding mechanism.
abstract: Bioadhesives are polymeric hydrogels that can adhere to a tissue after crosslinking and are an essential element in nearly all surgeries worldwide. Several bioadhesives are commercially available. However, none of them are ideal. The main limitation of current tissue adhesives is the tradeoff between biocompatibility and mechanical strength, especially in wet hemorrhagic environments. Our novel bioadhesives are based on the natural polymers gelatin (coldwater fish) and alginate, crosslinked by carbodiimide (EDC). Two types of hemostatic agents with a layered silicate structure, montmorillonite (MMT) and kaolin, were loaded in order to improve the sealing ability in a hemorrhagic environment. The effect of the adhesive's components on its mechanical strength was studied by three different methods - burst strength, lap shear and compression. The viscosity, gelation time and structural features of the adhesive were also studied. A qualitative model that describes the effect of the bioadhesive's parameters on the cohesive and adhesive strength was developed. A formulation based on 400mg/mL gelatin, 10mg/mL alginate and 20mg/mL EDC was found as optimal, enabling a burst strength of 387mmHg. Incorporation of kaolin increased the burst strength by 25% due to microcomposite structuring, whereas MMT increased the burst strength by 50% although loaded in a smaller concentration, due to nano-structuring effects. This research clearly shows that the incorporation of kaolin and MMT in gelatin-alginate surgical sealants is a very promising novel approach for improving the bonding strength and physical properties of surgical sealants for use in hemorrhagic environments.
  
  
  
  The current manuscript focuses on novel bioadhesives, based on natural polymers and loaded with hemostatic agents with a layered silicate structure, in order to improve the sealing ability in hemorrhagic environment. Such composite bioadhesives have not been developed and studied before. The effect of the adhesive's components on its mechanical strength was studied by three different methods, as well as the physical properties and structural features. Thorough understanding of these unique biomaterials resulted in a qualitative model which describes the effect of the bioadhesive's parameters on the cohesive and adhesive strength. Thus, structure-property-function relationships are presented. Structuring of the composite bioadhesives and its effect of the properties and bonding mechanism, are expected to be of high interest to Acta readership.
authors.affiliation: Dept. of Materials Science and Engineering, Faculty of Engineering, Tel-Aviv University, Tel-Aviv 69978, Israel.
authors.forename: Oded
authors.initials: O
authors.lastname: Pinkas
authors.affiliation: Dept. of Biomedical Engineering, Faculty of Engineering, Tel-Aviv University, Tel-Aviv 69978, Israel.
authors.forename: Daniella
authors.initials: D
authors.lastname: Goder
authors.affiliation: Dept. of Biomedical Engineering, Faculty of Engineering, Tel-Aviv University, Tel-Aviv 69978, Israel.
authors.forename: Roni
authors.initials: R
authors.lastname: Noyvirt
authors.affiliation: Dept. of Biomedical Engineering, Faculty of Engineering, Tel-Aviv University, Tel-Aviv 69978, Israel.
authors.forename: Sivan
authors.initials: S
authors.lastname: Peleg
authors.affiliation: Dept. of Biomedical Engineering, Faculty of Engineering, Tel-Aviv University, Tel-Aviv 69978, Israel.
authors.forename: Maayan
authors.initials: M
authors.lastname: Kahlon
authors.affiliation: Dept. of Materials Science and Engineering, Faculty of Engineering, Tel-Aviv University, Tel-Aviv 69978, Israel; Dept. of Biomedical Engineering, Faculty of Engineering, Tel-Aviv University, Tel-Aviv 69978, Israel. Electronic address: meitalz@post.tau.ac.il.
authors.forename: Meital
authors.initials: M
authors.lastname: Zilberman
mesh_terms: D000268:Adhesiveness; D000464:Alginates / Q000494:pharmacology; D000538:Aluminum Silicates / Q000737:chemistry; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D000077215:Clay; D005399:Fishes; D005780:Gelatin / Q000494:pharmacology; D020723:Glucuronic Acid / Q000494:pharmacology; D006490:Hemostatics / Q000494:pharmacology; D006603:Hexuronic Acids / Q000494:pharmacology; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry* / Q000494:pharmacology*; D007616:Kaolin / Q000737:chemistry; D034421:Sus scrofa; D013997:Time Factors; D014014:Tissue Adhesives / Q000737:chemistry* / Q000494:pharmacology*; D014783:Viscosity; D014961:X-Ray Diffraction
chemical_list: D000464:Alginates; D000538:Aluminum Silicates; D006490:Hemostatics; D006603:Hexuronic Acids; D014014:Tissue Adhesives; D007616:Kaolin; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D020723:Glucuronic Acid; D005780:Gelatin; D000077215:Clay
keywords: Kaolin; Montmorillonite; Tissue adhesives