Browse > Article
http://dx.doi.org/10.5125/jkaoms.2019.45.3.123

Postulated release profile of recombinant human bone morphogenetic protein-2 (rhBMP-2) from demineralized dentin matrix  

Um, In-Woong (R&D Institute)
Ku, Jeong-Kui (Department of Oral and Maxillofacial Surgery, Section of Dentistry, Armed Forces Capital Hospital)
Lee, Bu Kyu (Department of Oral and Maxillofacial Surgery, Seoul Asan Medical Center)
Yun, Pil-Young (Department of Oral and Maxillofacial Surgery, Section of Dentistry, Seoul National University Bundang Hospital)
Lee, Jeong Keun (Department of Oral and Maxillofacial Surgery, Institute of Oral Health Science, Ajou University School of Medicine)
Nam, Jeong-Hun (Department of Dental Implant/Oral Surgery, Private Clinic)
Publication Information
Journal of the Korean Association of Oral and Maxillofacial Surgeons / v.45, no.3, 2019 , pp. 123-128 More about this Journal
Abstract
Demineralized dentin matrix (DDM) has been used as a recombinant human bone morphogenetic protein-2 (rhBMP-2) carrier in many clinical trials. To optimize the clinical safety and efficacy of rhBMP-2 with DDM, efforts have been made to improve the delivery of rhBMP-2 by 1) lowering the administered dose, 2) localizing the protein, and 3) prolonging its retention time at the action site as well as the bone forming capacity of the carrier itself. The release profile of rhBMP-2 that is associated with endogenous BMP in dentin has been postulated according to the type of incorporation, which is attributed to the loosened interfibrillar space and nanoporous dentinal tubule pores. Physically adsorbed and modified, physically entrapped rhBMP-2 is sequentially released from the DDM surface during the early stage of implantation. As DDM degradation progresses, the loosened interfibrillar space and enlarged dentinal tubules release the entrapped rhBMP-2. Finally, the endogenous BMP in dentin is released with osteoclastic dentin resorption. According to the postulated release profile, DDM can therefore be used in a controlled manner as a sequential delivery scaffold for rhBMP-2, thus sustaining the rhBMP-2 concentration for a prolonged period due to localization. In addition, we attempted to determine how to lower the rhBMP-2 concentration to 0.2 mg/mL, which is lower than the approved 1.5 mg/mL.
Keywords
Collagen; Bone morphogenetic proteins; Demineralized dentin matrix;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Urist MR. Bone: formation by autoinduction. Science 1965;150:893-9.   DOI
2 Urist MR, Dowell TA, Hay PH, Strates BS. Inductive substrates for bone formation. Clin Orthop Relat Res 1968;59:59-96.
3 Wozney JM, Rosen V, Celeste AJ, Mitsock LM, Whitters MJ, Kriz RW, et al. Novel regulators of bone formation: molecular clones and activities. Science 1988;242:1528-34.   DOI
4 Reddi AH. Role of morphogenetic proteins in skeletal tissue engineering and regeneration. Nat Biotechnol 1998;16:247-52.   DOI
5 Kim SY, Kim YK, Park YH, Park JC, Ku JK, Um IW, et al. Evaluation of the healing potential of demineralized dentin matrix fixed with recombinant human bone morphogenetic protein-2 in bone grafts. Materials (Basel) 2017;10:E1049.   DOI
6 Kim YK, Um IW, Murata M. Tooth bank system for bone regeneration: safety report. J Hard Tissue Biol 2014;23:371-6.   DOI
7 Nakabayashi N, Pashley DH. Hybridization of dental hard tissues. Tokyo: Quintessence Publishing; 1998.
8 Garberoglio R, Brannstrom M. Scanning electron microscopic investigation of human dentinal tubules. Arch Oral Biol 1976;21:355-62.   DOI
9 Goldberg M, Kulkarni AB, Young M, Boskey A. Dentin: structure, composition and mineralization. Front Biosci (Elite Ed) 2011;3:711-35.   DOI
10 Iohara K, Nakashima M, Ito M, Ishikawa M, Nakasima A, Akamine A. Dentin regeneration by dental pulp stem cell therapy with recombinant human bone morphogenetic protein 2. J Dent Res 2004;83:590-5.   DOI
11 Luginbuehl V, Meinel L, Merkle HP, Gander B. Localized delivery of growth factors for bone repair. Eur J Pharm Biopharm 2004;58:197-208.   DOI
12 Um IW, Kim YK, Park JC, Lee JH. Clinical application of autogenous demineralized dentin matrix loaded with recombinant human bone morphogenetic-2 for socket preservation: a case series. Clin Implant Dent Relat Res 2019;21:4-10.
13 Vennat E, Bogicevic C, Fleureau JM, Degrange M. Demineralized dentin 3D porosity and pore size distribution using mercury porosimetry. Dent Mater 2009;25:729-35.   DOI
14 Um IW, Kim YK, Jun SH, Kim MY, Cui N. Demineralized dentin matrix as a carrier of recombinant human bone morphogenetic proteins: in vivo study. J Hard Tissue Biol 2018;27:219-26.   DOI
15 Olthof MGL, Kempen DHR, Liu X, Dadsetan M, Tryfonidou MA, Yaszemski MJ, et al. Bone morphogenetic protein-2 release profile modulates bone formation in phosphorylated hydrogel. J Tissue Eng Regen Med 2018;12:1339-51.   DOI
16 Miyaji H, Kawanami M. Dentin conditioning with BMP for reconstruction of periodontal attachment. In: Murata M, Um IW, eds. Advances in oral tissue engineering. Chicago: Quintessence Publishing; 2014:19-24.
17 Kim YK, Um IW, An HJ, Kim KW, Hong KS, Murata M. Effects of demineralized dentin matrix used as an rhBMP-2 carrier for bone regeneration. J Hard Tissue Biol 2014;23:415-22.   DOI
18 Bessho K, Tanaka N, Matsumoto J, Tagawa T, Murata M. Human dentin-matrix-derived bone morphogenetic protein. J Dent Res 1991;70:171-5.   DOI
19 Murata M. Collagen biology for bone regenerative surgery. J Korean Assoc Oral Maxillofac Surg 2012;38:321-5.   DOI
20 Kim YK, Kim SG, Yun PY, Yeo IS, Jin SC, Oh JS, et al. Autogenous teeth used for bone grafting: a comparison with traditional grafting materials. Oral Surg Oral Med Oral Pathol Oral Radiol 2014;117:e39-45.   DOI
21 Pang KM, Um IW, Kim YK, Woo JM, Kim SM, Lee JH. Autogenous demineralized dentin matrix from extracted tooth for the augmentation of alveolar bone defect: a prospective randomized clinical trial in comparison with anorganic bovine bone. Clin Oral Implants Res 2017;28:809-15.   DOI
22 Boyne PJ. Animal studies of application of rhBMP-2 in maxillofacial reconstruction. Bone 1996;19(1 Suppl):83S-92S.   DOI
23 Schilke R, Lisson JA, Bauss O, Geurtsen W. Comparison of the number and diameter of dentinal tubules in human and bovine dentine by scanning electron microscopic investigation. Arch Oral Biol 2000;45:355-61.   DOI
24 Coutinho ET, d'Almeida JRM, Paciornik S. Evaluation of microstructural parameters of human dentin by digital image analysis. Mater Res 2007;10:153-9.   DOI
25 Haidar ZS, Hamdy RC, Tabrizian M. Delivery of recombinant bone morphogenetic proteins for bone regeneration and repair. Part B: delivery systems for BMPs in orthopaedic and craniofacial tissue engineering. Biotechnol Lett 2009;31:1825-35.   DOI
26 Lee SH, Shin H. Matrices and scaffolds for delivery of bioactive molecules in bone and cartilage tissue engineering. Adv Drug Deliv Rev 2007;59:339-59.   DOI
27 Lo KW, Ulery BD, Ashe KM, Laurencin CT. Studies of bone morphogenetic protein-based surgical repair. Adv Drug Deliv Rev 2012;64:1277-91.   DOI
28 James AW, LaChaud G, Shen J, Asatrian G, Nguyen V, Zhang X, et al. A review of the clinical side effects of bone morphogenetic protein-2. Tissue Eng Part B Rev 2016;22:284-97.   DOI
29 U.S. Food and Drug Administration. Summary of safety and effectiveness data [Internet]. Silver Spring (MD): U.S. Food and Drug Administration 2007 Mar 9 [cited 2018 Dec 30]. Available from: https://www.accessdata.fda.gov/cdrh_docs/pdf5/P050053b.pdf.
30 Ike M, Urist MR. Recycled dentin root matrix for a carrier of recombinant human bone morphogenetic protein. J Oral Implantol 1998;24:124-32.   DOI
31 Fosse G, Saele PK, Eide R. Numerical density and distributional pattern of dentin tubules. Acta Odontol Scand 1992;50:201-10.   DOI
32 Murata M, Kawai T, Kawakami T, Akazawa T, Tazaki J, Ito K, et al. Human acid-insoluble dentin with BMP-2 accelerates bone induction in subcutaneous and intramuscular tissues. J Ceram Soc Jpn 2010;118:438-41.   DOI
33 Boyne PJ, James RA. Grafting of the maxillary sinus floor with autogenous marrow and bone. J Oral Surg 1980;38:613-6.
34 Moslemi N, Khoshkam V, Rafiei SC, Bahrami N, Aslroosta H. Outcomes of alveolar ridge preservation with recombinant human bone morphogenetic protein-2: a systematic review. Implant Dent 2018;27:351-62.   DOI
35 Kim KW. Bone induction by demineralized dentin matrix in nude mouse muscles. Maxillofac Plast Reconstr Surg 2014;36:50-6.   DOI
36 Tanoue R, Ohta K, Miyazono Y, Iwanaga J, Koba A, Natori T, et al. Three-dimensional ultrastructural analysis of the interface between an implanted demineralised dentin matrix and the surrounding newly formed bone. Sci Rep 2018;8:2858.   DOI
37 El Bialy I, Jiskoot W, Reza Nejadnik M. Formulation, delivery and stability of bone morphogenetic proteins for effective bone regeneration. Pharm Res 2017;34:1152-70.   DOI
38 Rumpler M, Wurger T, Roschger P, Zwettler E, Sturmlechner I, Altmann P, et al. Osteoclasts on bone and dentin in vitro: mechanism of trail formation and comparison of resorption behavior. Calcif Tissue Int 2013;93:526-39.   DOI