Evaluation of photo-crosslinked fibrinogen as a rapid and strong tissue adhesive.

Tissue adhesives and sealants are commonly used in surgery either as an adjunct to, or replacement for, sutures. Previously, we have shown that fibrinogen can be crosslinked rapidly to give a high-strength bond in the presence of a ruthenium(II) complex, a persulfate and irradiation with visible light, and that the crosslinked fibrinogen is nontoxic to cells in vitro. This approach addresses limitations to current fibrin sealants that typically have relatively slow curing times and low bond strengths. In the present study, we have evaluated the efficacy and safety of this new biological scaffold sealant in various animal models. When placed as solid implants into rats, the crosslinked fibrinogen persisted for at least 8 weeks but was fully resorbed by 18 weeks with minimal inflammatory responses. When used as a tissue adhesive for repair of skin incisions in rats or as an arterial haemostat in pig, the photo-crosslinked fibrinogen sealed tissue or arrested bleeding within 20 s of application. For the skin incisions, the fibrinogen sealant promoted rapid tissue vascularization and cellular infiltration with no adverse foreign body cell generation. New collagen deposition occurred and with time the matrix had remodelled to acquire large mature collagen fiber bundles which were accompanied by maximum regenerated tensile strength. This biomaterial system may find useful applications in surgical procedures where rapid curing and/or high strength tissue sealing is required.

[1]  T. Podor,et al.  Incorporation of Vitronectin into Fibrin Clots , 2002, The Journal of Biological Chemistry.

[2]  RICHARD A.F. CLARK,et al.  Fibrin and Wound Healing , 2001 .

[3]  P. Simpson‐Haidaris,et al.  Matrix-fibrinogen enhances wound closure by increasing both cell proliferation and migration. , 2003, Blood.

[4]  R. Brown,et al.  Wet extrusion of fibronectin-fibrinogen cables for application in tissue engineering. , 2001, Biotechnology and bioengineering.

[5]  M. Hincke,et al.  Fibrin: a versatile scaffold for tissue engineering applications. , 2008, Tissue engineering. Part B, Reviews.

[6]  S. Andreadis,et al.  Fibrin promotes migration in a three-dimensional in vitro model of wound regeneration. , 2002, Tissue engineering.

[7]  P. Koolwijk,et al.  Fibrin structure and wound healing , 2006, Journal of thrombosis and haemostasis : JTH.

[8]  S. Bergel.  Ueber Wirkungen des Fibrins , 1909 .

[9]  J. Soria,et al.  The role of fibroblasts in organization and degradation of a fibrin clot. , 1991, The Journal of laboratory and clinical medicine.

[10]  L. Medved,et al.  Interaction of the fibronectin COOH-terminal Fib-2 regions with fibrin: further characterization and localization of the Fib-2-binding sites. , 2007, Biochemistry.

[11]  E. Cronkite,et al.  USE OF THROMBIN AND FIBRINOGEN IN SKIN GRAFTING: PRELIMINARY REPORT , 1944 .

[12]  David G Simpson,et al.  Electrospun fibrinogen: feasibility as a tissue engineering scaffold in a rat cell culture model. , 2007, Journal of biomedical materials research. Part A.

[13]  C. Lewis,et al.  Fibrin fragment E stimulates the proliferation, migration and differentiation of human microvascular endothelial cells in vitro , 2004, Angiogenesis.

[14]  Timothy C. Hughes,et al.  The development of photochemically crosslinked native fibrinogen as a rapidly formed and mechanically strong surgical tissue sealant. , 2009, Biomaterials.

[15]  O. Malka,et al.  The binding of fibrin sealant to collagen is influenced by the method of purification and the cross-linked fibrinogen–fibronectin (heteronectin) content of the ‘fibrinogen’ component , 2005, Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis.

[16]  Meng-G Martin Lee,et al.  Applications of Fibrin Sealant in Surgery , 2005, Surgical innovation.

[17]  Catalina Wong,et al.  Fibrin-based biomaterials to deliver human growth factors , 2003, Thrombosis and Haemostasis.

[18]  H. Ohgushi,et al.  Efficacy of slow-releasing anticancer drug delivery systems on transplantable osteosarcomas in rats. , 1995, Japanese Journal of Clinical Oncology.

[19]  T. Kodadek,et al.  Chemistry for the analysis of protein-protein interactions: rapid and efficient cross-linking triggered by long wavelength light. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[20]  H. Kjaergård,et al.  Comparative kinetics of polymerisation of three fibrin sealants and influence on timing of tissue adhesion. , 2000, Thrombosis research.

[21]  Vogel Hg.  Tensile strength, relaxation and mechanical recovery in rat skin as influenced by maturation and age. , 1976 .

[22]  M. W. Peterson,et al.  CD1lb/CD 18 Mediates the Neutrophil Chemotactic Activity of Fibrin Degradation Product D Domain , 1997, Thrombosis and Haemostasis.

[23]  Alan W Eberhardt,et al.  Failure characteristics of multiple-component fibrin-based adhesives. , 2002, Journal of biomedical materials research.