J Korean Assoc Oral Maxillofac Surg 2019; 45(3): 123~128
Postulated release profile of recombinant human bone morphogenetic protein-2 (rhBMP-2) from demineralized dentin matrix
In-Woong Um1, Jeong-Kui Ku2,3, Bu Kyu Lee3, Pil-Young Yun4, Jeong Keun Lee5, Jeong-Hun Nam6
1R&D Institute, Korea Tooth Bank, Seoul,
2Department of Oral and Maxillofacial Surgery, Section of Dentistry, Armed Forces Capital Hospital, Seongnam,
3Department of Oral and Maxillofacial Surgery, Seoul Asan Medical Center, Seoul,
4Department of Oral and Maxillofacial Surgery, Section of Dentistry, Seoul National University Bundang Hospital, Seongnam,
5Department of Oral and Maxillofacial Surgery, Institute of Oral Health Science, Ajou University School of Medicine, Suwon,
6Department of Dental Implant/Oral Surgery, Private Clinic, Seoul, Korea
Jeong-Kui Ku
Department of Oral and Maxillofacial Surgery, Section of Dentistry, Armed Forces Capital Hospital, 81 Saemaeul-ro 177beon-gil, Bundang-gu, Seongnam 13574, Korea
TEL: +82-31-725-6184 FAX: +82-31-706-0987
E-mail: kujk123@gmail.com
ORCID: https://orcid.org/0000-0003-1192-7066

In-Woong Um
R&D Institute, Korea Tooth Bank, 622 Eonju-ro, Gangnam-gu, Seoul 06101, Korea
TEL: +82-2-548-2055 FAX: +82-2-548-2228
Email: h-bmp@hanmail.net
ORCID: https://orcid.org/0000-0002-4628-3662
Received March 25, 2019; Revised May 28, 2019; Accepted May 28, 2019.; Published online June 30, 2019.
© The Korean Association of Oral and Maxillofacial Surgeons.. All rights reserved.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
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

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