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In TERM, healing promotive factors are necessary to regulate the several important events during healing. An ideal treatment strategy should provide osteoconduction, osteoinduction, osteogenesis, and osteointegration of the graft or biomaterials within the healing bone. Since many materials have osteoconductive properties, only a few biomaterials have osteoinductive properties which are important for osteogenesis and osteointegration. Bone morphogenetic proteins (BMPs) are potent inductors of the osteogenic and angiogenic activities during bone repair. The BMPs can regulate the production and activity of some growth factors which are necessary for the osteogenesis. Since the introduction of BMP, it has added a valuable tool to the surgeon's possibilities and is most commonly used in bone defects. Despite significant evidences suggesting their potential benefit on bone healing, there are some evidences showing their side effects such as ectopic bone formation, osteolysis and problems related to cost effectiveness. Bone tissue engineering may create a local environment, using the delivery systems, which enables BMPs to carry out their activities and to lower cost and complication rate associated with BMPs. This review represented the most important concepts and evidences regarding the role of BMPs on bone healing and regeneration from basic to clinical application. The major advantages and disadvantages of such biologic compounds together with the BMPs substitutes are also discussed. \u00a9 2014 BioFactors, 40(5):459\u2013481, 2014<\/jats:p>","DOI":"10.1002\/biof.1177","type":"journal-article","created":{"date-parts":[[2014,10,4]],"date-time":"2014-10-04T01:23:43Z","timestamp":1412385823000},"page":"459-481","source":"Crossref","is-referenced-by-count":151,"title":["Bone morphogenetic proteins: A powerful osteoinductive compound with non\u2010negligible side effects and limitations"],"prefix":"10.1002","volume":"40","author":[{"given":"Ahmad","family":"Oryan","sequence":"first","affiliation":[{"name":"Department of Pathology School of Veterinary Medicine, Shiraz University Shiraz Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soodeh","family":"Alidadi","sequence":"additional","affiliation":[{"name":"Department of Pathology School of Veterinary Medicine, Shiraz University Shiraz Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Moshiri","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences Division of Surgery and Radiology School of Veterinary Medicine Shiraz University Shiraz Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amin","family":"Bigham\u2010Sadegh","sequence":"additional","affiliation":[{"name":"Department of Surgery and Radiology School of Veterinary Medicine, Shahrekord University Shahrekord Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,10,4]]},"reference":[{"key":"e_1_2_3_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2012.10.005"},{"key":"e_1_2_3_3_1","doi-asserted-by":"publisher","DOI":"10.13172\/2050-2303-2-2-374"},{"key":"e_1_2_3_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11914-014-0187-2"},{"key":"e_1_2_3_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0020-1383(13)70009-3"},{"key":"e_1_2_3_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1445-2197.2012.06316.x"},{"key":"e_1_2_3_7_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0073016"},{"key":"e_1_2_3_8_1","doi-asserted-by":"publisher","DOI":"10.13172\/2050-2303-1-2-291"},{"key":"e_1_2_3_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10856-013-5110-3"},{"key":"e_1_2_3_10_1","doi-asserted-by":"publisher","DOI":"10.4172\/2161-0673.1000126"},{"key":"e_1_2_3_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jamcollsurg.2013.03.025"},{"key":"e_1_2_3_12_1","doi-asserted-by":"publisher","DOI":"10.3109\/03008207.2012.660585"},{"key":"e_1_2_3_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2014.02.010"},{"key":"e_1_2_3_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2013.05.030"},{"key":"e_1_2_3_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/1749-799X-9-18"},{"key":"e_1_2_3_16_1","first-page":"91","article-title":"Bone morphogenetic proteins: a review","volume":"2","author":"Babu B. 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