Organ Repair, Hemostasis, and In Vivo Bonding of Medical Devices by Aqueous Solutions of Nanoparticles**

Sutures are traumatic to soft connective tissues, such as liver or lungs. Polymer tissue adhesives require complex in vivo control of polymerization or cross-linking reactions and currently suffer from being toxic, weak, or inefficient within the wet conditions of the body. Herein, we demonstrate using Stöber silica or iron oxide nanoparticles that nanobridging, that is, adhesion by aqueous nanoparticle solutions, can be used in vivo in rats to achieve rapid and strong closure and healing of deep wounds in skin and liver. Nanoparticles were also used to fix polymer membranes to tissues even in the presence of blood flow, such as occurring after liver resection, yielding permanent hemostasis within a minute. Furthermore, medical devices and tissue engineering constructs were fixed to organs such as a beating heart. The simplicity, rapidity, and robustness of nanobridging bode well for clinical applications, surgery, and regenerative medicine.

[1]  H. Mo,et al.  Unusual lesions of the rectum and anus. , 1951 .

[2]  S. Uranüs,et al.  Hemostatic Methods for the Management of Spleen and Liver Injuries , 1996, World Journal of Surgery.

[3]  A. Singer,et al.  Cutaneous wound healing. , 1999, The New England journal of medicine.

[4]  H. Kjaergård,et al.  Suture support: is it advantageous? , 2001, American journal of surgery.

[5]  A. Little,et al.  The influence of pulmonary staple line reinforcement on air leaks. , 2002, Chest.

[6]  A. Singer,et al.  Closure of lacerations and incisions with octylcyanoacrylate: a multicenter randomized controlled trial. , 2002, Surgery.

[7]  Riyi Shi,et al.  Adhesive strength of marine mussel extracts on porcine skin. , 2003, Biomaterials.

[8]  R. Marugán,et al.  Fibrin-glue sealed liver biopsy in patients with a liver transplantation or in liver transplantation waiting list: preliminary results , 2003 .

[9]  C. Thompson,et al.  Tissue Adhesives: A Review , 2006 .

[10]  Jens-Uwe Stolzenburg,et al.  Efficacy and safety of TachoSil as haemostatic treatment versus standard suturing in kidney tumour resection: a randomised prospective study. , 2007, European urology.

[11]  T. Treasure,et al.  Can tissue adhesives and glues significantly reduce the incidence and length of postoperative air leaks in patients having lung resections? , 2007, Interactive cardiovascular and thoracic surgery.

[12]  F. Berrevoet,et al.  Use of Topical Hemostatic Agents during Liver Resection , 2007, Digestive Surgery.

[13]  D. Gouma,et al.  Prevention of Biliary Leakage after Partial Liver Resection Using Topical Hemostatic Agents , 2007, Digestive Surgery.

[14]  Bruce P. Lee,et al.  A reversible wet/dry adhesive inspired by mussels and geckos , 2007, Nature.

[15]  R. Misra,et al.  Biomaterials , 2008 .

[16]  Robert Langer,et al.  A biodegradable and biocompatible gecko-inspired tissue adhesive , 2008, Proceedings of the National Academy of Sciences.

[17]  N. Katkhouda Application of fibrin glue after hepatectomy might still be justified. , 2008, Annals of surgery.

[18]  F. Chaubet,et al.  A Novel Cross‐linked Poly(vinyl alcohol) (PVA) for Vascular Grafts , 2008 .

[19]  A. Singer,et al.  The cyanoacrylate topical skin adhesives. , 2008, The American journal of emergency medicine.

[20]  S. Burks,et al.  Hemostats, sealants, and adhesives: components of the surgical toolbox , 2008, Transfusion.

[21]  M. Rahalkar,et al.  Chest , 2009, Indian Journal of Radiology and Imaging.

[22]  R. Rosenfeld Nature , 2009, Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery.

[23]  P. Messersmith,et al.  Biological performance of mussel-inspired adhesive in extrahepatic islet transplantation. , 2010, Biomaterials.

[24]  Florence Gazeau,et al.  Degradability of superparamagnetic nanoparticles in a model of intracellular environment: follow-up of magnetic, structural and chemical properties , 2010, Nanotechnology.

[25]  Jan Deprest,et al.  Injectable candidate sealants for fetal membrane repair: bonding and toxicity in vitro. , 2010, American journal of obstetrics and gynecology.

[26]  S. Burks,et al.  State-of-the-Art Review: Hemostats, Sealants, and Adhesives II: Update As Well As How and When to Use the Components of the Surgical Toolbox , 2010, Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis.

[27]  Bruce P. Lee,et al.  Mussel-Inspired Adhesives and Coatings. , 2011, Annual review of materials research.

[28]  J. Gugenheim,et al.  A randomized controlled trial comparing fibrin glue and PlasmaJet on the raw surface of the liver after hepatic resection. , 2011, Hepato-gastroenterology.

[29]  Riaz Agha,et al.  A review of the role of mechanical forces in cutaneous wound healing. , 2011, The Journal of surgical research.

[30]  F. Gendron,et al.  Long term in vivo biotransformation of iron oxide nanoparticles. , 2011, Biomaterials.

[31]  João C. Bordado,et al.  Surgical adhesives: Systematic review of the main types and development forecast , 2012 .

[32]  Jean-Baptiste Michel,et al.  Mesenchymal stem cell delivery into rat infarcted myocardium using a porous polysaccharide-based scaffold: a quantitative comparison with endocardial injection. , 2012, Tissue engineering. Part A.

[33]  P. Messersmith,et al.  The present and future of biologically inspired adhesive interfaces and materials. , 2012, Langmuir : the ACS journal of surfaces and colloids.

[34]  D. Madoff,et al.  Percutaneous Portal Vein Access and Transhepatic Tract Hemostasis , 2012, Seminars in Interventional Radiology.

[35]  William D Spotnitz,et al.  Hemostats, sealants, and adhesives III: a new update as well as cost and regulatory considerations for components of the surgical toolbox , 2012, Transfusion.

[36]  E. Mazza,et al.  Mussel-mimetic tissue adhesive for fetal membrane repair: an ex vivo evaluation. , 2012, Acta biomaterialia.

[37]  M. Mehdizadeh,et al.  Injectable citrate-based mussel-inspired tissue bioadhesives with high wet strength for sutureless wound closure. , 2012, Biomaterials.

[38]  R. Porte,et al.  Role of Fibrin Sealants in Liver Surgery , 2012, Digestive Surgery.

[39]  M. Devaud,et al.  How cellular processing of superparamagnetic nanoparticles affects their magnetic behavior and NMR relaxivity. , 2012, Contrast media & molecular imaging.

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

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

[42]  C. Mao,et al.  Systematic review and meta-analysis of application of fibrin sealant after liver resection , 2013, Current medical research and opinion.

[43]  Devin G. Barrett,et al.  Mechanically Robust, Negative‐Swelling, Mussel‐Inspired Tissue Adhesives , 2013, Advanced healthcare materials.

[44]  E Mazza,et al.  Mussel mimetic tissue adhesive for fetal membrane repair: initial in vivo investigation in rabbits. , 2013, European journal of obstetrics, gynecology, and reproductive biology.

[45]  Wei Nie,et al.  Rapidly in situ forming chitosan/ε-polylysine hydrogels for adhesive sealants and hemostatic materials. , 2013, Carbohydrate polymers.

[46]  A. Gnanamani,et al.  Rejoining of cut wounds by engineered gelatin-keratin glue. , 2013, Biochimica et biophysica acta.

[47]  Jian Yang,et al.  Design strategies and applications of tissue bioadhesives. , 2013, Macromolecular bioscience.

[48]  Jun Nie,et al.  Photocrosslinkable bioadhesive based on dextran and PEG derivatives. , 2014, Materials science & engineering. C, Materials for biological applications.

[49]  D. Buckley,et al.  Severe dermatitis from Dermabond® surgical glue , 2014, The British journal of dermatology.

[50]  Robert Langer,et al.  A Blood-Resistant Surgical Glue for Minimally Invasive Repair of Vessels and Heart Defects , 2014, Science Translational Medicine.

[51]  Ben Newland,et al.  Mussel-inspired hyperbranched poly(amino ester) polymer as strong wet tissue adhesive. , 2014, Biomaterials.

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