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

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.

[1]  R. Daynes,et al.  The antigenicity of soluble porcine elastins: I. Measurement of antibody by a radioimmunoassay. , 1977, Connective tissue research.

[2]  J Engel,et al.  Shapes, domain organizations and flexibility of laminin and fibronectin, two multifunctional proteins of the extracellular matrix. , 1981, Journal of molecular biology.

[3]  G. Waring,et al.  Isolation and characterization of fibronectin from bovine aqueous humor. , 1982, Investigative ophthalmology & visual science.

[4]  Erkki Ruoslahti,et al.  Cell attachment activity of fibronectin can be duplicated by small synthetic fragments of the molecule , 1984, Nature.

[5]  B. Boughton,et al.  The biochemical and functional heterogeneity of circulating human plasma fibronectin. , 1984, Biochemical and biophysical research communications.

[6]  B. Starcher Elastin and the lung. , 1986, Thorax.

[7]  John V. White,et al.  The architecture of adventitial elastin in the canine infrarenal aorta , 1991, The Anatomical record.

[8]  D. Hochstrasser,et al.  The focusing positions of polypeptides in immobilized pH gradients can be predicted from their amino acid sequences , 1993, Electrophoresis.

[9]  S. Hamada,et al.  Adherence of Porphyromonas gingivalis to matrix proteins via a fimbrial cryptic receptor exposed by its own arginine‐specific protease , 1997, Molecular microbiology.

[10]  D. Leahy Implications of atomic-resolution structures for cell adhesion. , 1997, Annual review of cell and developmental biology.

[11]  A. Subramanian,et al.  Dot-blot analysis of the degree of covalent modification of proteins and antibodies at amino groups. , 1997, Journal of immunological methods.

[12]  S. Hamada,et al.  Specific interactions between Porphyromonas gingivalis fimbriae and human extracellular matrix proteins. , 1999, FEMS microbiology letters.

[13]  Y. Ikada,et al.  Sealing effect of rapidly curable gelatin-poly (L-glutamic acid) hydrogel glue on lung air leak. , 1999, The Annals of thoracic surgery.

[14]  Min Jung Song,et al.  Characterization of porous collagen/hyaluronic acid scaffold modified by 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide cross-linking. , 2002, Biomaterials.

[15]  Bruce P. Lee,et al.  Synthesis and gelation of DOPA-modified poly(ethylene glycol) hydrogels. , 2002, Biomacromolecules.

[16]  M. Ishihara Photocrosslinkable Chitosan Hydrogel as a Wound Dressing and a Biological Adhesive , 2002 .

[17]  Stephen Mann,et al.  Physical properties of type I collagen extracted from fish scales of Pagrus major and Oreochromis niloticas. , 2003, International journal of biological macromolecules.

[18]  J. A. Federico,et al.  Fibrin glue in pulmonary resection: a prospective, randomized, blinded study. , 2003, The Annals of thoracic surgery.

[19]  D. Wood,et al.  Prospective randomized study evaluating a biodegradable polymeric sealant for sealing intraoperative air leaks that occur during pulmonary resection. , 2004, The Annals of thoracic surgery.

[20]  T. Taguchi,et al.  Physicochemical properties of gelatin gels prepared using citric acid derivative , 2004 .

[21]  T. Taguchi,et al.  Encapsulation of chondrocytes in injectable alkali-treated collagen gels prepared using poly(ethylene glycol)-based 4-armed star polymer. , 2005, Biomaterials.

[22]  J. Gotcher,et al.  Platelet Rich Plasma (PRP) , 2005 .

[23]  E. Blackstone,et al.  Characterization and importance of air leak after lobectomy. , 2005, The Annals of thoracic surgery.

[24]  T. Nagayasu,et al.  Creation of a uniform pleural defect model for the study of lung sealants. , 2007, The Journal of thoracic and cardiovascular surgery.

[25]  T. Matsuda,et al.  Elastomeric surgical sealant for hemostasis of cardiovascular anastomosis under full heparinization. , 2007, European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery.

[26]  T. Taguchi,et al.  Characterization of alkali-treated collagen gels prepared by different crosslinkers , 2008, Journal of materials science. Materials in medicine.

[27]  Rajeev Bhat,et al.  Fish gelatin: properties, challenges, and prospects as an alternative to mammalian gelatins , 2009 .

[28]  P. Dubruel,et al.  Affinity study of novel gelatin cell carriers for fibronectin. , 2009, Macromolecular bioscience.

[29]  Manabu Kinoshita,et al.  Adhesive, Flexible, and Robust Polysaccharide Nanosheets Integrated for Tissue‐Defect Repair , 2009 .

[30]  Masaru Yoshida,et al.  High-water-content mouldable hydrogels by mixing clay and a dendritic molecular binder , 2010, Nature.

[31]  Surgical sealant for preventing air leaks after pulmonary resections in patients with lung cancer. , 2010, AORN journal.

[32]  L. Borthwick,et al.  Lung epithelial wound healing in health and disease , 2010, Expert review of respiratory medicine.

[33]  K. Suemasu,et al.  The efficacy and side effects of gelatin-resorcinol formaldehyde-glutaraldehyde (GRFG) glue for preventing and sealing pulmonary air leakage , 2010, Surgery Today.

[34]  G. Grunkemeier,et al.  What is the inpatient cost of hospital complications or death after lobectomy or pneumonectomy? , 2011, The Annals of thoracic surgery.

[35]  Tae Gwan Park,et al.  Catechol-functionalized chitosan/pluronic hydrogels for tissue adhesives and hemostatic materials. , 2011, Biomacromolecules.

[36]  Pierre Weiss,et al.  An injectable vehicle for nucleus pulposus cell-based therapy. , 2011, Biomaterials.

[37]  Elizabeth Cosgriff-Hernandez,et al.  Development of a biostable replacement for PEGDA hydrogels. , 2012, Biomacromolecules.

[38]  J. Hasenkam,et al.  Comparative study of lung sealants in a porcine ex vivo model. , 2012, The Annals of thoracic surgery.

[39]  A. Klijian A novel approach to control air leaks in complex lung surgery: a retrospective review , 2012, Journal of Cardiothoracic Surgery.

[40]  M. Matsuda,et al.  Enhanced tissue penetration-induced high bonding strength of a novel tissue adhesive composed of cholesteryl group-modified gelatin and disuccinimidyl tartarate. , 2012, Colloids and surfaces. B, Biointerfaces.

[41]  Bharat Bhushan,et al.  Bioadhesion: a review of concepts and applications , 2012, Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences.

[42]  Brett E. Bouma,et al.  A Bio-Inspired Swellable Microneedle Adhesive for Mechanical Interlocking with Tissue , 2013, Nature Communications.

[43]  Vani Konda,et al.  Tissue adhesives: cyanoacrylate glue and fibrin sealant. , 2013, Gastrointestinal endoscopy.

[44]  R. Hoy,et al.  Effect of Particle Size, Temperature, and Deformation Rate on the Plastic Flow and Strain Hardening Response of PMMA Composites , 2013 .

[45]  Ludwik Leibler,et al.  Organ Repair, Hemostasis, and In Vivo Bonding of Medical Devices by Aqueous Solutions of Nanoparticles** , 2014, Angewandte Chemie.

[46]  S. Hyon,et al.  Low cytotoxic tissue adhesive based on oxidized dextran and epsilon-poly-L-lysine. , 2014, Journal of biomedical materials research. Part A.

[47]  T. Taguchi,et al.  Enhanced Bonding Strength of Hydrophobically Modified Gelatin Films on Wet Blood Vessels , 2014, International journal of molecular sciences.

[48]  J. V. Hest,et al.  The chemistry of tissue adhesive materials , 2014 .

[49]  Ellen M. Green,et al.  The structure and micromechanics of elastic tissue , 2014, Interface Focus.

[50]  T. Taguchi,et al.  Crosslinking Liposomes/Cells Using Cholesteryl Group-Modified Tilapia Gelatin , 2014, International journal of molecular sciences.

[51]  T. Sakai,et al.  “Nonswellable” Hydrogel Without Mechanical Hysteresis , 2014, Science.

[52]  L. Leibler,et al.  Nanoparticle solutions as adhesives for gels and biological tissues , 2013, Nature.

[53]  C. Roy,et al.  Self‐Adjustable Adhesion of Polyampholyte Hydrogels , 2015, Advanced materials.

[54]  M. Grinstaff,et al.  The chemistry and engineering of polymeric hydrogel adhesives for wound closure: a tutorial. , 2015, Chemical Society reviews.

[55]  Soong Ho Um,et al.  Tissue Adhesive Catechol‐Modified Hyaluronic Acid Hydrogel for Effective, Minimally Invasive Cell Therapy , 2015 .

[56]  T. Taguchi,et al.  Enhanced angiogenesis of growth factor-free porous biodegradable adhesive made with hexanoyl group-modified gelatin. , 2015, Biomaterials.

[57]  Xing-jie Liang,et al.  Inorganic Nanomaterials as Carriers for Drug Delivery. , 2016, Journal of biomedical nanotechnology.

[58]  Linyong Zhu,et al.  Tissue‐Integratable and Biocompatible Photogelation by the Imine Crosslinking Reaction , 2016, Advanced materials.

[59]  Robust Sealing of Blood Vessels with Cholesteryl Group-Modified, Alaska Pollock-Derived Gelatin-Based Biodegradable Sealant Under Wet Conditions. , 2016, Journal of biomedical nanotechnology.