title: Nonactivated versus thrombin-activated platelets on wound healing and fibroblast-to-myofibroblast differentiation in vivo and in vitro.
abstract: BACKGROUND
  Platelet preparations for tissue healing are usually preactivated before application to deliver concentrated growth factors. In this study, the authors investigated the differences between nonactivated and thrombin-activated platelets in wound healing.
  
  
  METHODS
  The healing effects (i.e., wound closure, myofibroblast formation, and angiogenesis) of nonactivated and thrombin-activated platelets were compared in experimental wounds in diabetic (db/db) animals. In vitro, fibroblast phenotype and function were tested in response to platelets and activated platelets. No treatment served as a negative control.
  
  
  RESULTS
  Wounds treated with platelets reached 90 percent closure after 15 days, faster than activated platelets (26 days), and with higher levels of myofibroblasts and angiogenesis. In vitro, platelets enhanced cell migration and induced two-fold higher myofibroblast differentiation and contraction compared with activated platelets.
  
  
  CONCLUSIONS
  Platelets stimulate wound healing more efficiently compared with activated platelets by enhancing fibroblast differentiation and contractile function. Similar levels of growth factors may induce different biological effects when delivered "on demand" rather than in an initial bolus.
authors.affiliation: Lausanne and Geneva, Switzerland; Boston, Mass.; and Toronto, Ontario, Canada From the Department of Plastic Surgery, University Hospitals of Lausanne; the Department of Plastic, Reconstructive, and Aesthetic Surgery, University Hospitals of Geneva and Faculty of Medicine, University of Geneva; the Laboratory of Cell Biophysics, Ecole Polytechnique Fédérale de Lausanne; the Tissue Engineering and Wound Healing Laboratory, Brigham and Women's Hospital; and the Laboratory of Tissue Repair and Regeneration, Matrix Dynamics Group, Faculty of Dentistry, University of Toronto.
authors.forename: Sandra S
authors.initials: SS
authors.lastname: Scherer
authors.forename: Mickael
authors.initials: M
authors.lastname: Tobalem
authors.forename: Enrico
authors.initials: E
authors.lastname: Vigato
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Heit
authors.forename: Ali
authors.initials: A
authors.lastname: Modarressi
authors.forename: Boris
authors.initials: B
authors.lastname: Hinz
authors.forename: Brigitte
authors.initials: B
authors.lastname: Pittet
authors.forename: Giorgio
authors.initials: G
authors.lastname: Pietramaggiori
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002465:Cell Movement / Q000502:physiology; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D005347:Fibroblasts / Q000502:physiology*; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D058628:Myofibroblasts / Q000502:physiology; D018919:Neovascularization, Physiologic; D015539:Platelet Activation / Q000502:physiology*; D053657:Platelet-Rich Plasma / Q000502:physiology*; D013917:Thrombin / Q000378:metabolism; D014945:Wound Healing / Q000502:physiology*
chemical_list: D013917:Thrombin