title: Platelet-rich plasma for the treatment of bone defects: from pre-clinical rational to evidence in the clinical practice. A systematic review.
abstract: The treatment of large bone defects represents a significant challenge for orthopaedic surgeons. In recent years, biologic agents have also been used to further improve bone healing. Among these, platelet-rich plasma (PRP) is the most exploited strategy. The aim of the present study was to systematically review the available literature to identify: 1) preclinical in-vivo results supporting the rational of PRP use for bone healing; 2) evidence from the clinical practice on the actual clinical benefit of PRP for the treatment of fractures and complications such as delayed unions and non-unions.
  
  
  
  A systematic review of the literature was performed on the application of PRP in bone healing, using the following inclusion criteria: pre-clinical and clinical reports of any level of evidence, written in English language, published in the last 20 years (1996-2016), on the use of PRP to stimulate long-bone defect treatment, with focus on fracture and delayed/non-unions healing.
  
  
  
  The search in the Pubmed database identified 64 articles eligible for inclusion: 45 were preclinical in-vivo studies and 19 were clinical studies. Despite the fact that the overall pre-clinical results seem to support the benefit of PRP in 91.1 % of the studies, a more in depth analysis underlined a lower success rate, with a positive outcome of 84.4 % in terms of histological analysis, and even lower values considering radiological and biomechanical results (75.0 % and 72.7 % positive outcome respectively). This was also mirrored in the clinical literature, where the real benefit of PRP use to treat fractures and non-unions is still under debate.
  
  
  
  Overall, the available literature presents major limitations in terms of low quality and extreme heterogeneity, which hamper the possibility to optimize PRP treatment and translate it into a real clinical benefit despite positive preclinical findings on its biological potential to favour bone healing.
authors.affiliation: Nano-Biotechnology Laboratory, Rizzoli Orthopaedic Institute, Via di Barbiano 1/10, 40136, Bologna, Italy.
authors.forename: Alice
authors.initials: A
authors.lastname: Roffi
authors.affiliation: Nano-Biotechnology Laboratory, Rizzoli Orthopaedic Institute, Via di Barbiano 1/10, 40136, Bologna, Italy. berardo.dimatteo@gmail.com.|I Orthopaedic and Traumatologic Clinic, Rizzoli Orthopaedic Institute, Via Pupilli 1, 40136, Bologna, Italy. berardo.dimatteo@gmail.com.
authors.forename: Berardo
authors.initials: B
authors.lastname: Di Matteo
authors.affiliation: Nano-Biotechnology Laboratory, Rizzoli Orthopaedic Institute, Via di Barbiano 1/10, 40136, Bologna, Italy.
authors.forename: Gopal Shankar
authors.initials: GS
authors.lastname: Krishnakumar
authors.affiliation: Nano-Biotechnology Laboratory, Rizzoli Orthopaedic Institute, Via di Barbiano 1/10, 40136, Bologna, Italy.
authors.forename: Elizaveta
authors.initials: E
authors.lastname: Kon
authors.affiliation: Biomechanics Laboratory, Rizzoli Orthopaedic Institute, Via di Barbiano 1/10, 40136, Bologna, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Filardo
mesh_terms: D000818:Animals; D001842:Bone and Bones / Q000187:drug effects / Q000503:physiopathology*; D050723:Fractures, Bone / Q000188:drug therapy*; D006801:Humans; D053657:Platelet-Rich Plasma / Q000187:drug effects*; D014945:Wound Healing / Q000187:drug effects*
keywords: Bone defect; Bone healing; Fracture; Growth factors; Non-union; PRP