Plastic and Reconstructive Surgery Non-activated versus thrombin-activated platelets on wound healing and fibroblast-to- myofibroblast differentiation in vivo and in vitro --Manuscript Draft-- Manuscript Number: PRS-D-11-00906R2 Full Title: Non-activated versus thrombin-activated platelets on wound healing and fibroblast-to- myofibroblast differentiation in vivo and in vitro Article Type: Original Article Corresponding Author: Sandra Saja Scherer, MD Divison of Plastic Surgery, Brigham and Women's Hospital, Harvard Medical School Boston, MA UNITED STATES Corresponding Author Secondary Information: Corresponding Author's Institution: Divison of Plastic Surgery, Brigham and Women's Hospital, Harvard Medical School Corresponding Author's Secondary Institution: First Author: Sandra Saja Scherer, MD First Author Secondary Information: All Authors: Sandra Saja Scherer, MD Mickael Tobalem, MD Enrico Vigato, MD Yvonne Heit, MD Ali Modarressi, MD Boris Hinz, PhD Brigitte Pittet, MD Giorgio Pietramaggiori, MD, PhD All Authors Secondary Information: Abstract: Introduction. Platelet preparations for tissue healing are usually pre-activated prior application to deliver concentrated growth factors. Here, we investigate the differences between non-activated and thrombin-activated platelets in wound healing. Methods. The healing effects (wound closure, myofibroblast formation and angiogenesis) of non-activated 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 negative control. Results. Wounds treated with platelets reached 90% closure after 15 days, faster than activated platelets (26 days), and with higher levels myofibroblasts and angiogenesis. In vitro, platelets enhanced cell migration and induced two-fold higher myofibroblast differentiation and contraction, compared to activated platelets. Conclusions. Platelets stimulate wound healing more efficiently compared to 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. Response to Reviewers: Required documents were completed and sent by fax the 7th of July 2011. Powered by Editorial Manager® and Preprint Manager® from Aries Systems Corporation