title: Components of the plasminogen activation system promote engraftment of porous polyethylene biomaterial via common and distinct effects.
abstract: Rapid fibrovascularization is a prerequisite for successful biomaterial engraftment. In addition to their well-known roles in fibrinolysis, urokinase-type plasminogen activator (uPA) and tissue plasminogen activator (tPA) or their inhibitor plasminogen activator inhibitor-1 (PAI-1) have recently been implicated as individual mediators in non-fibrinolytic processes, including cell adhesion, migration, and proliferation. Since these events are critical for fibrovascularization of biomaterial, we hypothesized that the components of the plasminogen activation system contribute to biomaterial engraftment. Employing in vivo and ex vivo microscopy techniques, vessel and collagen network formation within porous polyethylene (PPE) implants engrafted into dorsal skinfold chambers were found to be significantly impaired in uPA-, tPA-, or PAI-1-deficient mice. Consequently, the force required for mechanical disintegration of the implants out of the host tissue was significantly lower in the mutant mice than in wild-type controls. Conversely, surface coating with recombinant uPA, tPA, non-catalytic uPA, or PAI-1, but not with non-catalytic tPA, accelerated implant vascularization in wild-type mice. Thus, uPA, tPA, and PAI-1 contribute to the fibrovascularization of PPE implants through common and distinct effects. As clinical perspective, surface coating with recombinant uPA, tPA, or PAI-1 might provide a novel strategy for accelerating the vascularization of this biomaterial.
authors: Department of Otorhinolaryngology, Head and Neck Surgery, Ludwig-Maximilians-Universität München, Munich, Germany; Walter Brendel Centre of Experimental Medicine, Ludwig-Maximilians-Universität München, Munich, Germany.
authors: Christoph A
authors: CA
authors: Reichel
authors: Department of Otorhinolaryngology, Head and Neck Surgery, Ludwig-Maximilians-Universität München, Munich, Germany; Walter Brendel Centre of Experimental Medicine, Ludwig-Maximilians-Universität München, Munich, Germany.
authors: Maximilian E T
authors: ME
authors: Hessenauer
authors: Department of Pharmacy, Ludwig-Maximilians-Universität München, Munich, Germany.
authors: Kerstin
authors: K
authors: Pflieger
authors: Walter Brendel Centre of Experimental Medicine, Ludwig-Maximilians-Universität München, Munich, Germany.
authors: Markus
authors: M
authors: Rehberg
authors: Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
authors: Sandip M
authors: SM
authors: Kanse
authors: Department of Pharmacy, Ludwig-Maximilians-Universität München, Munich, Germany.
authors: Stefan
authors: S
authors: Zahler
authors: Walter Brendel Centre of Experimental Medicine, Ludwig-Maximilians-Universität München, Munich, Germany.
authors: Fritz
authors: F
authors: Krombach
authors: Department of Otorhinolaryngology, Head and Neck Surgery, Ludwig-Maximilians-Universität München, Munich, Germany.
authors: Alexander
authors: A
authors: Berghaus
authors: Department of Otorhinolaryngology, Head and Neck Surgery, Johannes Gutenberg University Medical Center, Mainz, Germany.
authors: Sebastian
authors: S
authors: Strieth
mesh_terms: D000818:Animals; D001672:Biocompatible Materials; D020099:Coated Materials, Biocompatible / Q000494:pharmacology; D003094:Collagen / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells; D020007:Implants, Experimental; D007962:Leukocytes / Q000378:metabolism; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D018919:Neovascularization, Physiologic / Q000187:drug effects; D020959:Polyethylene; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D058258:Serpin E2 / Q000235:genetics / Q000378:metabolism*; D010959:Tissue Plasminogen Activator / Q000235:genetics / Q000378:metabolism*; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics / Q000378:metabolism*
chemical_list: D001672:Biocompatible Materials; D020099:Coated Materials, Biocompatible; D011994:Recombinant Proteins; D058258:Serpin E2; C511869:Serpine2 protein, mouse; D020959:Polyethylene; D003094:Collagen; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator