Journal of Periodontal and Implant Science

Korean Academy of Periodontology (대한치주과학회)
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Bone regeneration using activin A/BMP2 chimera (AB204) with collagen membrane in rats with calvarial defects

  • Haeji Yum (Department of Periodontology, School of Dentistry and Dental Research Institute, Seoul National University and Seoul National University Dental Hospital) ;
  • Hee-seung Han (Department of Periodontology, School of Dentistry and Dental Research Institute, Seoul National University and Seoul National University Dental Hospital) ;
  • Jung-Tae Lee (One-Stop Specialty Center, Seoul National University, Dental Hospital) ;
  • Young-Dan Cho (Department of Periodontology, School of Dentistry and Dental Research Institute, Seoul National University and Seoul National University Dental Hospital) ;
  • Sungtae Kim (Department of Periodontology, School of Dentistry and Dental Research Institute, Seoul National University and Seoul National University Dental Hospital)
  • Received : 2023.10.11
  • Accepted : 2024.01.05
  • Published : 2024.10.30
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Abstract

Purpose: Collagen has long been recognized as an excellent carrier for growth factors, and membrane-type collagen has been widely applied in dentistry for guided bone regeneration. This study was conducted to examine the effects of an activin A/BMP2 chimera (AB204) combined with a collagen membrane (CM) on bone repair in a rat calvarial defect model. Methods: A unilateral calvarial defect measuring 5.0 mm was surgically created in 32 Sprague-Dawley rats. The rats were then randomly assigned to 1 of 4 groups, each consisting of 8 animals: control (untreated), CM (treated with a CM only), CM/bone morphogenetic protein 2 (BMP2) (treated with a CM and 1.0 ㎍ of BMP2), and CM/AB204 (treated with a CM and 1.0 ㎍ of AB204). Bone regeneration was evaluated using micro-computed tomography (CT) and histological analysis at 2 and 4 weeks following surgery. Results: Micro-CT analysis revealed that bone formation in the CM/BMP2 and CM/AB204 groups was superior to that observed in the control and CM groups at both 2 and 4 weeks postoperatively. BMP2 induced greater bone regeneration than AB204 at 2 weeks; however, AB204 resulted in a greater bone volume at 4 weeks, achieving the highest values recorded. No significant differences were found between the CM/BMP2 and CM/AB204 groups at either time point (P>0.05). On histological examination, new bone formation was evident in both CM/BMP2 and CM/AB204 groups. Conclusions: Within the limitations of this study, the findings indicate that AB204 may enhance osteogenic potential when used in combination with CM for bone regeneration.

Keywords

Acknowledgement

This research was supported by the New Faculty Startup Fund from Seoul National University and a grant from the National Research Foundation of Korea (NRF), funded by the Ministry of Science and ICT (MSIT) of the Korean government (No. 2020R1C1C1005830/2022M3A9F3082330).

References

  1. Retzepi M, Donos N. Guided bone regeneration: biological principle and therapeutic applications. Clin Oral Implants Res 2010;21:567-76.
  2. Nevins M, Camelo M, Nevins ML, Schenk RK, Lynch SE. Periodontal regeneration in humans using recombinant human platelet-derived growth factor-BB (rhPDGF-BB) and allogenic bone. J Periodontol 2003;74:1282-92.
  3. Dimitriou R, Mataliotakis GI, Calori GM, Giannoudis PV. The role of barrier membranes for guided bone regeneration and restoration of large bone defects: current experimental and clinical evidence. BMC Med 2012;10:81.
  4. Sbricoli L, Guazzo R, Annunziata M, Gobbato L, Bressan E, Nastri L. Selection of collagen membranes for bone regeneration: a literature review. Materials (Basel) 2020;13:786.
  5. Ortolani E, Quadrini F, Bellisario D, Santo L, Polimeni A, Santarsiero A. Mechanical qualification of collagen membranes used in dentistry. Ann Ist Super Sanita 2015;51:229-35. PUBMED
  6. De Marco AC, Jardini MA, Modolo F, Nunes FD, de Lima LA. Immunolocalization of bone morphogenetic protein 2 during the early healing events after guided bone regeneration. Oral Surg Oral Med Oral Pathol Oral Radiol 2012;113:533-41.
  7. Omar O, Elgali I, Dahlin C, Thomsen P. Barrier membranes: more than the barrier effect? J Clin Periodontol 2019;46 Suppl 21:103-23.
  8. Urist MR, Huo YK, Brownell AG, Hohl WM, Buyske J, Lietze A, et al. Purification of bovine bone morphogenetic protein by hydroxyapatite chromatography. Proc Natl Acad Sci U S A 1984;81:371-5.
  9. Notodihardjo FZ, Kakudo N, Kushida S, Suzuki K, Kusumoto K. Bone regeneration with BMP-2 and hydroxyapatite in critical-size calvarial defects in rats. J Craniomaxillofac Surg 2012;40:287-91.
  10. Lim HC, Paeng KW, Jung UW, Benic GI. Vertical bone augmentation using collagenated or non-collagenated bone substitute materials with or without recombinant human bone morphogenetic protein-2 in a rabbit calvarial model. J Periodontal Implant Sci 2023;53:429-43.
  11. Jovanovic SA, Hunt DR, Bernard GW, Spiekermann H, Wozney JM, Wikesjo UM. Bone reconstruction following implantation of rhBMP-2 and guided bone regeneration in canine alveolar ridge defects. Clin Oral Implants Res 2007;18:224-30.
  12. Hunt DR, Jovanovic SA, Wikesjo UM, Wozney JM, Bernard GW. Hyaluronan supports recombinant human bone morphogenetic protein-2 induced bone reconstruction of advanced alveolar ridge defects in dogs. A pilot study. J Periodontol 2001;72:651-8.
  13. Krishnakumar GS, Roffi A, Reale D, Kon E, Filardo G. Clinical application of bone morphogenetic proteins for bone healing: a systematic review. Int Orthop 2017;41:1073-83.
  14. Lee JH, Yu CH, Yang JJ, Baek HR, Lee KM, Koo TY, et al. Comparative study of fusion rate induced by different dosages of Escherichia coli-derived recombinant human bone morphogenetic protein-2 using hydroxyapatite carrier. Spine J 2012;12:239-48.
  15. Subbiah R, Guldberg RE. Materials science and design principles of growth factor delivery systems in tissue engineering and regenerative medicine. Adv Healthc Mater 2019;8:e1801000.
  16. Liu L, Lam WM, Yang Z, Wang M, Ren X, Hu T, et al. Improving the handling properties and long-term stability of polyelectrolyte complex by freeze-drying technique for low-dose bone morphogenetic protein 2 delivery. J Biomed Mater Res B Appl Biomater 2020;108:2450-60.
  17. Seeherman HJ, Berasi SP, Brown CT, Martinez RX, Juo ZS, Jelinsky S, et al. A BMP/activin A chimera is superior to native BMPs and induces bone repair in nonhuman primates when delivered in a composite matrix. Sci Transl Med 2019;11:eaar4953.
  18. Yonemori K, Imamura T, Ishidou Y, Okano T, Matsunaga S, Yoshida H, et al. Bone morphogenetic protein receptors and activin receptors are highly expressed in ossified ligament tissues of patients with ossification of the posterior longitudinal ligament. Am J Pathol 1997;150:1335-47.
  19. Derynck R, Zhang YE. Smad-dependent and Smad-independent pathways in TGF-beta family signalling. Nature 2003;425:577-84.
  20. Townson SA, Martinez-Hackert E, Greppi C, Lowden P, Sako D, Liu J, et al. Specificity and structure of a high affinity activin receptor-like kinase 1 (ALK1) signaling complex. J Biol Chem 2012;287:27313-25.
  21. Allendorph GP, Read JD, Kawakami Y, Kelber JA, Isaacs MJ, Choe S. Designer TGFβ superfamily ligands with diversified functionality. PLoS One 2011;6:e26402.
  22. Yoon BH, Esquivies L, Ahn C, Gray PC, Ye SK, Kwiatkowski W, et al. An activin A/BMP2 chimera, AB204, displays bone-healing properties superior to those of BMP2. J Bone Miner Res 2014;29:1950-9.
  23. Zheng GB, Lee JH, Jin YZ. In vitro and in vivo evaluation of osteoinductivity and bone fusion ability of an activin a/BMP2 chimera (AB204): a comparison study between AB204 and rhBMP-2. Growth Factors 2017;35:249-58.
  24. Caballe-Serrano J, Abdeslam-Mohamed Y, Munar-Frau A, Fujioka-Kobayashi M, Hernandez-Alfaro F, Miron R. Adsorption and release kinetics of growth factors on barrier membranes for guided tissue/bone regeneration: a systematic review. Arch Oral Biol 2019;100:57-68.
  25. Osidak EO, Osidak MS, Sivogrivov DE, Portnaya TS, Grunina TM, Galushkina ZM, et al. Kinetics of BMP-2 release from collagen carrier: evaluation by enzyme immunoassay in the presence of plasma proteins. Bull Exp Biol Med 2014;158:104-8.
  26. Ramalingam S, Al-Rasheed A, ArRejaie A, Nooh N, Al-Kindi M, Al-Hezaimi K. Guided bone regeneration in standardized calvarial defects using beta-tricalcium phosphate and collagen membrane: a real-time in vivo micro-computed tomographic experiment in rats. Odontology 2016;104:199-210.
  27. Park SY, Kim KH, Koo KT, Lee KW, Lee YM, Chung CP, et al. The evaluation of the correlation between histomorphometric analysis and micro-computed tomography analysis in AdBMP-2 induced bone regeneration in rat calvarial defects. J Periodontal Implant Sci 2011;41:218-26.
  28. Pelaez M, Susin C, Lee J, Fiorini T, Bisch FC, Dixon DR, et al. Effect of rhBMP-2 dose on bone formation/maturation in a rat critical-size calvarial defect model. J Clin Periodontol 2014;41:827-36.
  29. Lee EU, Lim HC, Hong JY, Lee JS, Jung UW, Choi SH. Bone regenerative efficacy of biphasic calcium phosphate collagen composite as a carrier of rhBMP-2. Clin Oral Implants Res 2016;27:e91-9.
  30. Donos N, Lang NP, Karoussis IK, Bosshardt D, Tonetti M, Kostopoulos L. Effect of GBR in combination with deproteinized bovine bone mineral and/or enamel matrix proteins on the healing of critical-size defects. Clin Oral Implants Res 2004;15:101-11.
  31. Hong I, Khalid AW, Pae HC, Song YW, Cha JK, Lee JS, et al. Diverse patterns of bone regeneration in rabbit calvarial defects depending on the type of collagen membrane. J Periodontal Implant Sci 2021;51:40-52.
  32. Jin X, Park JY, Lee JS, Jung UW, Choi SH, Cha JK. Tissue integration patterns of non-crosslinked and crosslinked collagen membranes: an experimental in vivo study. J Periodontal Implant Sci 2022;53:207-17.
  33. Gresham RC, Bahney CS, Leach JK. Growth factor delivery using extracellular matrix-mimicking substrates for musculoskeletal tissue engineering and repair. Bioact Mater 2021;6:1945-56.
  34. Krishnan L, Priddy LB, Esancy C, Klosterhoff BS, Stevens HY, Tran L, et al. Delivery vehicle effects on bone regeneration and heterotopic ossification induced by high dose BMP-2. Acta Biomater 2017;49:101-12.
  35. Ryu D, Yoon BH, Oh CH, Kim MH, Kim JY, Yoon SH, et al. Activin A/BMP2 chimera (AB204) exhibits better spinal bone fusion properties than rhBMP2. J Korean Neurosurg Soc 2018;61:669-79.
  36. Kolambkar YM, Dupont KM, Boerckel JD, Huebsch N, Mooney DJ, Hutmacher DW, et al. An alginate-based hybrid system for growth factor delivery in the functional repair of large bone defects. Biomaterials 2011;32:65-74.
  37. Ren X, Zhao M, Lash B, Martino MM, Julier Z. Growth factor engineering strategies for regenerative medicine applications. Front Bioeng Biotechnol 2020;7:469.