Enhanced Sealing by Hydrophobic Modification of Alaska Pollock‐Derived Gelatin‐Based Surgical Sealants for the Treatment of Pulmonary Air Leaks

Abstract

Pulmonary air leaks are medical complications of thoracic surgery for which fibrin sealant is the main treatment. In this study, innovative sealants based on hydrophobically modified Alaska pollock-derived gelatin (hm-ApGltn) and a poly(ethylene)glycol-based 4-armed cross-linker (4S-PEG) have been developed and their burst strengths have been evaluated using fresh rat lung. The developed sealants show higher lung burst strength compared with the nonmodified original ApGltn (Org-ApGltn)-based sealant and a commercial fibrin sealant. The maximum burst strength of the hm-ApGltn-based sealant is 1.6-fold higher than the Org-ApGltn-based sealant (n = 5, p < 0.05), and 2.1-fold higher than the commercial fibrin sealant (n = 5, p < 0.05). Cell culture experiments show that modification of ApGltn with cholesteryl or stearoyl groups effectively enhances anchoring to the cell surface. In addition, binding constants between hm-ApGltn and extracellular matrix proteins such as fibronectin and fibrillin are increased. Therefore, the new hm-ApGltn/4S-PEG-based sealant has the potential for applications in thoracic surgery.

Promotion of Cell Migration into a Hydrophobically modified Alaska Pollock Gelatin‐Based Hydrogel

“…The phenomenon considered that the overall cross‐linking density of the C6‐ApGltn hydrogel was not substantially decreased compared to that of the Org‐ApGltn hydrogel. In our previous study, the hydrophobically modified gelatin hydrogel showed a decreased swelling ratio due to the forming of physical cross‐linking and increased apparent cross‐linking density caused by intermolecular hydrophobic interaction . Compared to our previous study, the hydrophobicity of hydrophobically modified gelatin was relatively low.…”

“…In our previous study, the hydrophobically modified gelatin hydrogel showed a decreased swelling ratio due to the forming of physical cross-linking and increased apparent crosslinking density caused by intermolecular hydrophobic interaction. [31][32][33][34] Compared to our previous study, the hydrophobicity of hydrophobically modified gelatin was relatively low. Therefore, the overall cross-linking density of the Org-and C6-ApGltn hydrogel was considered to be almost equivalent.…”

Multifunctional Hydrophobized Microparticles for Accelerated Wound Healing after Endoscopic Submucosal Dissection

“…To achieve underwater adhesion, hydrophobic interactions that function only underwater would be a powerful tool. We have reported that hm‐Gltn dramatically enhanced the interfacial adhesion strength of hydrogels on wet living tissues through hydrophobic interactions . Moreover, it has been reported that inorganic nanoparticles functioned as an adhesive for hydrogels and biological tissues owing to the large surface area and high adsorption energy .…”

Hemostatic properties of in situ gels composed of hydrophobically modified biopolymers

“…The C18-ApGltn was synthesized by a nucleophilic substitution reaction of the amino group in ApGltn with stearoyl chloride following previous methods. [23][24][25] In brief, an ApGltn/DMSO solution with a gelatin concentration of 4 wt% was prepared. After adding TEA and stearoyl chloride to the ApGltn/DMSO solution, the mixture was stirred for 15 h at room temperature under a dry N 2 atmosphere.…”

“…HyA is an important component of the cardiac extracellular matrix, and can promote cell adhesion and proliferation by interacting with HA receptors on red blood cells. 20,21 Whereas hm-ApGltn was used to enhance the bulk properties and adhesiveness to living tissue surfaces, [22][23][24][25] and gelatin molecules can act like collagen in activating the intrinsic coagulation cascade. 8,26 Here, we report the synthesis, characterization and hemostatic properties of in situ gels composed of ald-hm-HyA and hm-ApGltn.…”