{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T19:40:47Z","timestamp":1781120447059,"version":"3.54.1"},"reference-count":81,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2022,7,4]],"date-time":"2022-07-04T00:00:00Z","timestamp":1656892800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Union\u2019s Horizon 2020 (H2020-EU.3.1.3.)","award":["874896"],"award-info":[{"award-number":["874896"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Long bone fractures display significant non-union rates, but the exact biological mechanisms implicated in this devastating complication remain unclear. The combination of osteogenetic and angiogenetic factors at the fracture site is an essential prerequisite for successful bone regeneration. The aim of this study is to investigate the results of the clinical implantation of growth factors for intraoperative enhancement of osteogenesis for the treatment of long bone fractures and non-unions. Methods: A systematic literature review search was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines in the PubMed and Web of Science databases from the date of inception of each database through to 10 January 2022. Specific inclusion and exclusion criteria were applied in order to identify relevant studies reporting on the treatment of upper and lower limb long bone non-unions treated with osteoinductive or cellular factors. Results: Overall, 18 studies met the inclusion criteria and examined the effectiveness of the application of Bone Morphogenetic Proteins-2 and -7 (BMPs), platelet rich plasma (PRP) and mesenchymal stem cells (MSCs). Despite the existence of limitations in the studies analysed (containing mixed groups of open and close fractures, different types of fractures, variability of treatment protocols, different selection criteria and follow-up periods amongst others), their overall effectiveness was found significantly increased in patients who received them compared with the controls (I2 = 60%, 95% CI = 1.59 [0.99\u20132.54], Z =1.93, p = 0.05). Conclusion: Administration of BMP-2 and -7, PRP and MSCs were considered effective and safe methods in fracture treatment, increasing bone consolidation, reducing time to repair and being linked to satisfactory postoperative functional scores.<\/jats:p>","DOI":"10.3390\/jcm11133901","type":"journal-article","created":{"date-parts":[[2022,7,4]],"date-time":"2022-07-04T11:15:05Z","timestamp":1656933305000},"page":"3901","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Therapeutic Efficacy and Safety of Osteoinductive Factors and Cellular Therapies for Long Bone Fractures and Non-Unions: A Meta-Analysis and Systematic Review"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3265-5522","authenticated-orcid":false,"given":"Angelos","family":"Kaspiris","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Pharmacology, Department of Pharmacy, School of Health Sciences, University of Patras, 26504 Patras, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1127-3421","authenticated-orcid":false,"given":"Argyris C.","family":"Hadjimichael","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics, St. Mary\u2019s Hospital, Imperial College Healthcare NHS Trust, Praed Street, London W2 1NY, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2428-5250","authenticated-orcid":false,"given":"Elias S.","family":"Vasiliadis","sequence":"additional","affiliation":[{"name":"Third Department of Orthopaedic Surgery, School of Medicine, \u201cKAT\u201d General Hospital, National and Kapodistrian University of Athens, 2 Nikis Street, 14561 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7676-6702","authenticated-orcid":false,"given":"Dionysios J.","family":"Papachristou","sequence":"additional","affiliation":[{"name":"Laboratory of Bone and Soft Tissue Studies, Department of Anatomy-Histology-Embryology, University Patras Medical School, 26504 Patras, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5205-7696","authenticated-orcid":false,"given":"Peter V.","family":"Giannoudis","sequence":"additional","affiliation":[{"name":"Academic Department of Trauma and Orthopaedics, School of Medicine, University of Leeds, Leeds LS7 4SA, UK"},{"name":"NIHR Leeds Biomedical Research Centre, Chapel Allerton Hospital, Leeds LS7 4SA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elias C.","family":"Panagiotopoulos","sequence":"additional","affiliation":[{"name":"Department of Trauma and Orthopaedics, Patras University Hospital and Medical School, 26504 Patras, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2306","DOI":"10.1007\/s11999-008-0416-z","article-title":"The Global Burden of Musculoskeletal Injuries: Challenges and Solutions","volume":"466","author":"Mock","year":"2008","journal-title":"Clin. 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