Enhanced Bone Regeneration by Bone Morphogenetic Protein-2 After Pretreatment with Low-Intensity Pulsed Ultrasound in Distraction Osteogenesis

Overview

Journal Tissue Eng Regen Med

Date 2022 May 20

PMID 35594008

Authors

Jeong Joon Han

Hoon Joo Yang

Soon Jung Hwang

Affiliations

Soon will be listed here.

Abstract

Background: Bone morphogenetic protein 2 (BMP-2) and low-intensity pulsed ultrasound (LIPUS) have been used to enhance bone healing in distraction osteogenesis (DO). The aim of this study was to assess the synergistic effect of BMP-2 and LIPUS on bone regeneration in DO and to determine the optimal treatment strategy for enhanced bone regeneration.

Methods: Rat mesenchymal stromal cells were treated with various application protocols of BMP-2 and LIPUS, and cell proliferation, alkaline phosphatase activity, and osteogenesis-related marker expression were evaluated. In vivo experiments were performed in a rabbit DO model according to the application protocols with different timings of BMP-2 and LIPUS application.

Results: Application of BMP-2 after LIPUS pretreatment (BMP-2 after LIPUS) showed greater cell proliferation than LIPUS treatment alone, and higher ALP activity than all other treatment protocols. BMP-2 after LIPUS also exhibited increased gene expression levels of ALP, Cbfa1, and Osterix compared with LIPUS treatment alone. In vivo experiments revealed no significant differences in bone healing based on the timing of LIPUS treatment in DO. The combination of BMP-2 and LIPUS resulted in increased bone volume and bone mineral density compared with BMP-2 or LIPUS. Regarding the timing of BMP-2 application, the application of BMP-2 after LIPUS pretreatment led to greater bone volume than the application of BMP-2 before LIPUS.

Conclusion: The results of this study suggest that the combined treatment of BMP-2 and LIPUS can lead to enhanced bone healing in DO and that effective bone healing can be achieved through the application of LIPUS before BMP-2.

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References

El-Bialy T, Royston T, Magin R, Evans C, el-Moneim Zaki A, Frizzell L . The effect of pulsed ultrasound on mandibular distraction. Ann Biomed Eng. 2003; 30(10):1251-61. DOI: 10.1114/1.1529196. View

Imafuji T, Shirakata Y, Shinohara Y, Nakamura T, Noguchi K . Enhanced bone formation of calvarial bone defects by low-intensity pulsed ultrasound and recombinant human bone morphogenetic protein-9: a preliminary experimental study in rats. Clin Oral Investig. 2021; 25(10):5917-5927. DOI: 10.1007/s00784-021-03897-6. View

Herford A, Boyne P . Reconstruction of mandibular continuity defects with bone morphogenetic protein-2 (rhBMP-2). J Oral Maxillofac Surg. 2008; 66(4):616-24. DOI: 10.1016/j.joms.2007.11.021. View

Sailhan F, Gleyzolle B, Parot R, Guerini H, Viguier E . Rh-BMP-2 in distraction osteogenesis: dose effect and premature consolidation. Injury. 2009; 41(7):680-6. DOI: 10.1016/j.injury.2009.10.010. View

Wijdicks C, Virdi A, Sena K, Sumner D, Leven R . Ultrasound enhances recombinant human BMP-2 induced ectopic bone formation in a rat model. Ultrasound Med Biol. 2009; 35(10):1629-37. DOI: 10.1016/j.ultrasmedbio.2009.04.017. View

Wang S, Lewallen D, Bolander M, Chao E, Ilstrup D, Greenleaf J . Low intensity ultrasound treatment increases strength in a rat femoral fracture model. J Orthop Res. 1994; 12(1):40-7. DOI: 10.1002/jor.1100120106. View

Viljanen V, Gao T, Lindholm T, Lindholm T, Kommonen B . Xenogeneic moose (Alces alces) bone morphogenetic protein (mBMP)-induced repair of critical-size skull defects in sheep. Int J Oral Maxillofac Surg. 1996; 25(3):217-222. DOI: 10.1016/s0901-5027(96)80034-8. View

SantAnna E, Leven R, Virdi A, Sumner D . Effect of low intensity pulsed ultrasound and BMP-2 on rat bone marrow stromal cell gene expression. J Orthop Res. 2005; 23(3):646-52. DOI: 10.1016/j.orthres.2004.09.007. View

Hadjiargyrou M, McLeod K, Ryaby J, Rubin C . Enhancement of fracture healing by low intensity ultrasound. Clin Orthop Relat Res. 1999; (355 Suppl):S216-29. DOI: 10.1097/00003086-199810001-00022. View

10.

Swennen G, Schliephake H, Dempf R, Schierle H, Malevez C . Craniofacial distraction osteogenesis: a review of the literature: Part 1: clinical studies. Int J Oral Maxillofac Surg. 2001; 30(2):89-103. DOI: 10.1054/ijom.2000.0033. View

11.

de Freitas R, Spin-Neto R, Marcantonio Junior E, Pereira L, Wikesjo U, Susin C . Alveolar ridge and maxillary sinus augmentation using rhBMP-2: a systematic review. Clin Implant Dent Relat Res. 2013; 17 Suppl 1:e192-201. DOI: 10.1111/cid.12156. View

12.

Parvizi J, Parpura V, Greenleaf J, Bolander M . Calcium signaling is required for ultrasound-stimulated aggrecan synthesis by rat chondrocytes. J Orthop Res. 2002; 20(1):51-7. DOI: 10.1016/S0736-0266(01)00069-9. View

13.

Schortinghuis J, Bronckers A, Stegenga B, Raghoebar G, de Bont L . Ultrasound to stimulate early bone formation in a distraction gap: a double blind randomised clinical pilot trial in the edentulous mandible. Arch Oral Biol. 2005; 50(4):411-20. DOI: 10.1016/j.archoralbio.2004.09.005. View

14.

Gao T, Lindholm T, Kommonen B, Ragni P, Paronzini A, Lindholm T . The use of a coral composite implant containing bone morphogenetic protein to repair a segmental tibial defect in sheep. Int Orthop. 1997; 21(3):194-200. PMC: 3617683. DOI: 10.1007/s002640050149. View

15.

Xie L, Wangrangsimakul K, Suttapreyasri S, Cheung L, Nuntanaranont T . A preliminary study of the effect of low intensity pulsed ultrasound on new bone formation during mandibular distraction osteogenesis in rabbits. Int J Oral Maxillofac Surg. 2011; 40(7):730-6. DOI: 10.1016/j.ijom.2011.03.016. View

16.

Cheung L, Zheng L . Effect of recombinant human bone morphogenetic protein-2 on mandibular distraction at different rates in an experimental model. J Craniofac Surg. 2006; 17(1):100-8. DOI: 10.1097/01.scs.0000188744.06723.1f. View

17.

Lai C, Chen S, Chiu L, Yang C, Tsai Y, Zuo C . Effects of low-intensity pulsed ultrasound, dexamethasone/TGF-beta1 and/or BMP-2 on the transcriptional expression of genes in human mesenchymal stem cells: chondrogenic vs. osteogenic differentiation. Ultrasound Med Biol. 2010; 36(6):1022-33. DOI: 10.1016/j.ultrasmedbio.2010.03.014. View

18.

Lou J, Xu F, Merkel K, Manske P . Gene therapy: adenovirus-mediated human bone morphogenetic protein-2 gene transfer induces mesenchymal progenitor cell proliferation and differentiation in vitro and bone formation in vivo. J Orthop Res. 1999; 17(1):43-50. DOI: 10.1002/jor.1100170108. View

19.

Selvamurugan N, Kwok S, Vasilov A, Jefcoat S, Partridge N . Effects of BMP-2 and pulsed electromagnetic field (PEMF) on rat primary osteoblastic cell proliferation and gene expression. J Orthop Res. 2007; 25(9):1213-20. DOI: 10.1002/jor.20409. View

20.

Han J, Chang A, Ahn J, Jung S, Hong J, Oh H . Efficacy and safety of rhBMP/β-TCP in alveolar ridge preservation: a multicenter, randomized, open-label, comparative, investigator-blinded clinical trial. Maxillofac Plast Reconstr Surg. 2021; 43(1):42. PMC: 8688599. DOI: 10.1186/s40902-021-00328-0. View