Abstract
Bone morphogenetic protein-2 (BMP-2) is a potent growth factor affecting bone formation. While recombinant human BMP-2 (rhBMP-2) has been commercially available in cases of non-union fracture and spinal fusion in orthopaedics, it has also been applied to improve bone regeneration in challenging cases requiring dental implant treatment. However, complications related to an initially high dosage for maintaining an effective physiological concentration at the defect site have been reported, although an effective and safe rhBMP-2 dosage for bone regeneration has not yet been determined. In contrast to protein delivery, BMP-2 gene transfer into the defect site induces BMP-2 synthesis in vivo and leads to secretion for weeks to months, depending on the vector, at a concentration of nanograms per milliliter. BMP-2 gene delivery is advantageous for bone wound healing process in terms of dosage and duration. However, safety concerns related to viral vectors are one of the hurdles that need to be overcome for gene delivery to be used in clinical practice. Recently, commercially available gene therapy has been introduced in orthopedics, and clinical trials in dentistry have been ongoing. This review examines the application of BMP-2 gene therapy for bone regeneration in the oral and maxillofacial regions and discusses future perspectives of BMP-2 gene therapy in dentistry.
Highlights
The adjunctive use of bone morphogenic protein 2 (BMP-2) has become clinically available to improve bone regeneration and produce predictable results in challenging cases
In 2007, the US Food and Drug Administration approved the use of recombinant human BMP-2 in dentistry for maxillary sinus grafting and bone-grafting procedures associated with extraction sockets [2]. rhBMP-2 is delivered into a defect with synthetic bone-grafting materials (e.g., β-tricalcium phosphate) or a collagen sponge for dental use
Since we previously confirmed that BMSCs and PDLSCs induce alveolar bone regeneration at a similar level [80], we applied PDLSCs for ex vivo BMP-2 gene delivery to restore the defects induced by peri-implantitis [39]
Summary
The adjunctive use of bone morphogenic protein 2 (BMP-2) has become clinically available to improve bone regeneration and produce predictable results in challenging cases. RhBMP-2 Delivery in Protein Form rshaepuagogvenrshamenepuCgagbeeovgeurneensemarnetCgrtaanebeeietcuorneniscarornettoertaanlnievryctbodnipecyrnoaiotarenvnlolrvybbeagdcpeoydiaeialtrnnvdaoolbiegebauncot-dilerhgtlenveaodreiesBbaanu,t-drlfMhgreatieveoirenfPnBsaauedd,-gfMrcs2taiebtionpnfPpdomuedrg-rencso2eoltebic-pdrpvcmoerprleerdenoiheolrncueci-yrooviecrpcrlneldseoeaihryssnucglyot,soirryaltcerusno.eanhyscmsgTld,BsttyhritasrMoe.ucehnunmlTcBdPiestnhisiMff-enoie2cceurnlPpaecihisns-tlfeieB2sfnirsecaMriotac-pihpusiftlPeBmpsdrr-asMlhioi2pitpe-euBfilPispdamdnMr-lnoh2iipwteetPnBhiilsdt-naiMei2tpnsohwtpePotnhdirrb-niteoeit2ipoohfstapeeednoldrcribvneooniteoeonstfasfoendet[uolail7cevonarblt–enmrsss1frottuobe[4a.il7gratb]olTu–.mresnor1ttnbee.ei4etegosT]urnr.eneoatohngeetreaesieronnrnceaonhcoegter,alrielonabbacntncgoooeie,olennrlannbbaeetgooioennnnee the amount of native BMP-2 that can be isolated from bone is limited (1–2 μg/kg cortical bone) [15], an innovative method, the recombinant BMP production technology developed. The amount of native BMP-2 that can be isolated from bone is limited (1–2 μg/kg cortical bone) [15], an innovative method, the recombinant BMP production technology developed by Wozney et al, enables the clinical use of rhBMP-2 [16]. A high initial dose of rhBMP-2 is applied to defects to maintain an effective in vivo concentration for the healing period because BMP-2 is a late-acting growth factor. Poynton and Lane mentioned concerns related to the use of rhBMP-2, such as the possibility of bony overgrowth, interaction with exposed dura, cancer risk, systemic toxicity, reproductive toxicity, immunogenicity, local toxicity, osteoclastic activation, and effects on distal organs [26]
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