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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)
  • Received : 2019.03.25
  • Accepted : 2019.05.28
  • Published : 2019.06.30

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

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