title: Enhanced regeneration of rabbit mandibular defects through a combined treatment of electrical stimulation and rhBMP-2 application.
abstract: We evaluated the new bone regeneration of a rabbit mandibular defect using hBMSCs under electrical stimulation combined with rhBMP-2 in this study. An inner scaffold prepared by setting a collagen sponge with hBMSCs and hydrogel was placed into a polycaprolactone (PCL) outer box, and an electrical stimulation device was installed between the inner scaffold and the outer box. There were three experimental groups depending on electrical stimulation and application of rhBMP-2. The experimental group was divided into the following three groups. Group 1, in which rhBMP-2 (5 μg/defect) was added to hydrogel and electrical stimulation was not applied; Group 2, in which rhBMP-2 (5 μg/defect) was added as in Group 1 and electrical stimulation was applied; and Group 3, in which electrical stimulation was applied and rhBMP-2 (5 μg/defect) was injected directly into defect site. The delivered electrical stimulation was charge-balanced bi-phasic electric current pulses, and electrical stimulation was conducted for 7 days. The stimulation parameters of the bi-phasic electrical current set at an amplitude of 20 μA, a duration of 100 μs and a frequency of 100 Hz. Four weeks after surgery, new bone formation in each group was evaluated using radiography, histology, and micro-computed tomography (μCT). Groups 2 and 3 exhibited a significant increase in new bone formation compared to Group 1, while Group 3 showed the highest level of new bone regeneration. In a comparison between two groups, Group 2 showed a higher bone volume (BV) by 260 % (p < 0.01) compared with Group 1, and Group 3 showed a higher BV by 442 % (p < 0.01) compared with Group 1. The trend of the bone surface density (ratio of new bone to the real defect volume, BS/TV), trabecular number, and connectivity was identical to that of the BV. The total bone mineral density (BMD) of Groups 2 and 3 showed values higher by the ratios of 103 % (p < 0.01) and 107.5 % (p < 0.01) compared with Group 1, respectively. Part BMD for Groups 2 and 3 showed higher values by the ratios of 104.9 % (p < 0.01) and 122.4 % (p < 0.01) compared with Group 1, respectively. These results suggest that the combined treatment of electrical stimulation, hBMSCs, a collagen sponge, hydrogel, and rhBMP-2 was effective for bone regeneration of large-size mandibular defects. The application of rhBMP-2 with an injection following electrical stimulation demonstrated better efficiency as regards bone regeneration.
authors: Department of Electrical and Computer Engineering, Seoul National University, Seoul, South Korea.
authors: Junghoon
authors: J
authors: Kim
authors: Hoon Joo
authors: HJ
authors: Yang
authors: Tae Hyung
authors: TH
authors: Cho
authors: Sung Eun
authors: SE
authors: Lee
authors: Yong Doo
authors: YD
authors: Park
authors: Hyun Man
authors: HM
authors: Kim
authors: In Sook
authors: IS
authors: Kim
authors: Young-kwon
authors: YK
authors: Seo
authors: Soon Jung
authors: SJ
authors: Hwang
authors: Sung June
authors: SJ
authors: Kim
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology*; D001861:Bone Regeneration / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D003094:Collagen; D004558:Electric Stimulation / Q000379:methods*; D008297:Male; D008334:Mandible / Q000000981:diagnostic imaging / Q000502:physiology; D008338:Mandibular Injuries / Q000628:therapy*; D045164:Mesenchymal Stem Cell Transplantation / Q000295:instrumentation / Q000379:methods; D059630:Mesenchymal Stem Cells; D011817:Rabbits; D011859:Radiography; D011994:Recombinant Proteins / Q000494:pharmacology*; D054457:Tissue Scaffolds
chemical_list: C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D011994:Recombinant Proteins; D003094:Collagen
references: J Cell Biol. 1994 Dec;127(6 Pt 1):1755-66
references: 7798324
references: Adv Drug Deliv Rev. 2003 Nov 28;55(12):1613-29
references: 14623404
references: Int J Low Extrem Wounds. 2005 Mar;4(1):23-44
references: 15860450
references: Annu Int Conf IEEE Eng Med Biol Soc. 2011;2011:3601-4
references: 22255118
references: Nat Biotechnol. 2003 Sep;21(9):1025-32
references: 12949568
references: Tissue Eng Part A. 2013 Jan;19(1-2):66-78
references: 23083133
references: Nat Biotechnol. 2000 Sep;18(9):959-63
references: 10973216
references: J Orthop Res. 1994 Mar;12(2):262-7
references: 8164100
references: Biomaterials. 2000 Jun;21(11):1129-34
references: 10817265
references: Trends Genet. 1994 Jan;10(1):16-21
references: 8146910
references: J Bone Joint Surg Am. 1989 Feb;71(2):228-36
references: 2783931
references: Biomaterials. 2003 Aug;24(18):2977-84
references: 12895569
references: Biomaterials. 2007 Apr;28(10):1830-7
references: 17208295
references: Biomed Mater. 2012 Jun;7(3):035002
references: 22358865
references: J Orthop Sci. 2005 Sep;10(5):529-33
references: 16193367
references: Wound Repair Regen. 1999 Nov-Dec;7(6):495-503
references: 10633009
references: Tissue Eng Part A. 2011 Feb;17(3-4):337-48
references: 20868206
references: Biochim Biophys Acta. 2006 Sep;1763(9):907-16
references: 16930744
references: Physiol Genomics. 2008 Mar 14;33(1):33-40
references: 18198281
references: Clin Oral Implants Res. 2012 Apr;23(4):467-73
references: 21443590
references: Bone. 2004 Aug;35(2):562-9
references: 15268909
references: J Cell Sci. 2004 Jan 26;117(Pt 3):397-405
references: 14679307
references: J Cell Physiol. 1988 Jan;134(1):37-46
references: 2447105
references: Biomaterials. 2006 Jul;27(20):3738-44
references: 16530826
references: J Bone Miner Res. 2005 May;20(5):848-57
references: 15824858
references: Biomaterials. 2010 May;31(13):3684-93
references: 20149926
references: Biomaterials. 2011 Apr;32(11):2851-61
references: 21288570
references: Biomaterials. 2007 Oct;28(29):4240-50
references: 17644173