title: Effect of alkyl chain length on the interfacial strength of surgical sealants composed of hydrophobically-modified Alaska-pollock-derived gelatins and poly(ethylene)glycol-based four-armed crosslinker.
abstract: Surgical sealants are widely used clinically. Fibrin sealant is a commonly used sealant, but is ineffective under wet conditions during surgery. In this study, we developed surgical sealants composed of hydrophobically modified Alaska-pollock-derived gelatins (hm-ApGltns) with different alkyl chain lengths from C3 to C18 and a poly(ethylene)glycol-based 4-armed crosslinker (4S-PEG). The burst strength of the hm-ApGltns-based sealant was evaluated using a fresh porcine blood vessel and was found to increase with increasing alkyl chain length from 167±22 to 299±43mmHg when the substitution ratio of amino groups of ApGltn was around 10mol%. The maximum burst strength was observed when stearoyl-group modified ApGltn (Ste-ApGltn)/4S-PEG-based sealant was used, displaying 3-fold higher burst strength than the original ApGltn (Org-ApGltn)/4S-PEG sealant, and 10-fold higher than the commercial fibrin sealant. Ste-ApGltn/4S-PEG-based sealant was biodegraded in rat subcutaneous tissue within 8 weeks without severe inflammation. By molecular interaction analysis using surface plasmon resonance, the binding constant of Ste-ApGltn to fibronectin was found to be 9-fold higher than that of Org-ApGltn. Therefore, the developed sealant, in particular the Ste-ApGltn/4S-PEG-based sealant, has potential applications in the field of cardiovascular surgery as well as thoracic surgery.
authors.affiliation: Graduate School of Pure and Applied Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8577, Japan; Polymeric Biomaterials Group, Biomaterials Field, Research Center for Functional Materials, National Institute for Materials Science, 1-1 Namiki, Tsukuba, Ibaraki 305-0044, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Mizuta
authors.affiliation: Graduate School of Pure and Applied Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8577, Japan; Polymeric Biomaterials Group, Biomaterials Field, Research Center for Functional Materials, National Institute for Materials Science, 1-1 Namiki, Tsukuba, Ibaraki 305-0044, Japan.
authors.forename: Temmei
authors.initials: T
authors.lastname: Ito
authors.affiliation: Graduate School of Pure and Applied Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8577, Japan; Polymeric Biomaterials Group, Biomaterials Field, Research Center for Functional Materials, National Institute for Materials Science, 1-1 Namiki, Tsukuba, Ibaraki 305-0044, Japan. Electronic address: taguchi.tetsushi@nims.go.jp.
authors.forename: Tetsushi
authors.initials: T
authors.lastname: Taguchi
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000737:chemistry* / Q000187:drug effects; D003432:Cross-Linking Reagents / Q000737:chemistry*; D005260:Female; D015718:Fibrin Tissue Adhesive / Q000008:administration & dosage / Q000737:chemistry*; D005780:Gelatin / Q000008:administration & dosage / Q000737:chemistry*; D005977:Glutarates / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D007249:Inflammation / Q000517:prevention & control*; D008813:Mice, Inbred ICR; D011092:Polyethylene Glycols / Q000737:chemistry*; D051381:Rats; D013552:Swine; D013718:Tensile Strength; D014014:Tissue Adhesives / Q000737:chemistry*
chemical_list: D003432:Cross-Linking Reagents; D015718:Fibrin Tissue Adhesive; D005977:Glutarates; D014014:Tissue Adhesives; C499599:pentaerythritol poly(ethylene glycol) ether tetrasuccinimidyl glutarate; D011092:Polyethylene Glycols; D005780:Gelatin
keywords: Adhesion; Alaska-pollock-derived gelatin; Hydrophobically-modified gelatin; Poly(ethylene)glycol; Sealant