본문 바로가기
KERD
논문KCI 등재

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

0

조회

0

다운로드

5

인용

0

참고문헌

키워드

주제분류치의학

초록

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.

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.

참고문헌 (38)

  1. Urist MR, "Bone : formation by autoinduction", Science, 150, pp.893~899 (1965)
  2. Urist MR, "Inductive substrates for bone formation", Clin Orthop Relat Res, 59, pp.59~96 (1968)
  3. Wozney JM, "Novel regulators of bone formation : molecular clones and activities", Science, 242, pp.1528~1534 (1988)
  4. Reddi AH, "Role of morphogenetic proteins in skeletal tissue engineering and regeneration", Nat Biotechnol, 16, pp.247~252 (1998)
  5. Boyne PJ, "Grafting of the maxillary sinus floor with autogenous marrow and bone", J Oral Surg, 38, pp.613~616 (1980)
  6. Moslemi N, "Outcomes of alveolar ridge preservation with recombinant human bone morphogenetic protein-2 : a systematic review", Implant Dent, 27, pp.351~362 (2018)
  7. Haidar ZS, "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, 31, pp.1825~1835 (2009)
  8. Boyne PJ., "Animal studies of application of rhBMP-2 in maxillofacial reconstruction", Bone, 19(1 Suppl), pp.83S~92S (1996)
  9. Lee SH, "Matrices and scaffolds for delivery of bioactive molecules in bone and cartilage tissue engineering", Adv Drug Deliv Rev, 59, pp.339~359 (2007)
  10. Lo KW, "Studies of bone morphogenetic protein-based surgical repair", Adv Drug Deliv Rev, 64, pp.1277~1291 (2012)
  11. James AW, "A review of the clinical side effects of bone morphogenetic protein-2", Tissue Eng Part B Rev, 22, pp.284~297 (2016)
  12. "Summary of safety and effectiveness data" (2007)[URL]
  13. Ike M, "Recycled dentin root matrix for a carrier of recombinant human bone morphogenetic protein", J Oral Implantol, 24, pp.124~132 (1998)
  14. Murata M, "Human acid-insoluble dentin with BMP-2 accelerates bone induction in subcutaneous and intramuscular tissues", J Ceram Soc Jpn, 118, pp.438~441 (2010)
  15. Miyaji H, "Advances in oral tissue engineering", pp.19~24 (2014), Quintessence Publishing
  16. Kim YK, "Effects of demineralized dentin matrix used as an rhBMP-2 carrier for bone regeneration", J Hard Tissue Biol, 23, pp.415~422 (2014)
  17. Um IW, "Demineralized dentin matrix as a carrier of recombinant human bone morphogenetic proteins : in vivo study", J Hard Tissue Biol, 27, pp.219~226 (2018)
  18. Bessho K, "Human dentin-matrix-derived bone morphogenetic protein", J Dent Res, 70, pp.171~175 (1991)
  19. Masaru Murata, "Collagen biology for bone regenerative surgery", 대한구강악안면외과학회지, 38(6), pp.321~325 (2012), 대한구강악안면외과학회
  20. Kim YK, "Autogenous teeth used for bone grafting : a comparison with traditional grafting materials", Oral Surg Oral Med Oral Pathol Oral Radiol, 117, pp.e39~e45 (2014)
  21. Pang KM, "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, 28, pp.809~815 (2017)
  22. Schilke R, "Comparison of the number and diameter of dentinal tubules in human and bovine dentine by scanning electron microscopic investigation", Arch Oral Biol, 45, pp.355~361 (2000)
  23. Coutinho ET, "Evaluation of microstructural parameters of human dentin by digital image analysis", Mater Res, 10, pp.153~159 (2007)
  24. Goldberg M, "Dentin: structure, composition and mineralization", Front Biosci(Elite Ed), 3, pp.711~735 (2011)
  25. Iohara K, "Dentin regeneration by dental pulp stem cell therapy with recombinant human bone morphogenetic protein 2", J Dent Res, 83, pp.590~595 (2004)
  26. Kim SY, "Evaluation of the healing potential of demineralized dentin matrix fixed with recombinant human bone morphogenetic protein-2 in bone grafts", Materials (Basel), 10, pp.E1049~ (2017)
  27. Kim YK, "Tooth bank system for bone regeneration : safety report", J Hard Tissue Biol, 23, pp.371~376 (2014)
  28. Nakabayashi N, "Hybridization of dental hard tissues" (1998), Quintessence Publishing
  29. Garberoglio R, "Scanning electron microscopic investigation of human dentinal tubules", Arch Oral Biol, 21, pp.355~362 (1976)
  30. Luginbuehl V, "Localized delivery of growth factors for bone repair", Eur J Pharm Biopharm, 58, pp.197~208 (2004)
  31. Um IW, "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, 21, pp.4~10 (2019)
  32. Vennat E, "Demineralized dentin 3D porosity and pore size distribution using mercury porosimetry", Dent Mater, 25, pp.729~735 (2009)
  33. Olthof MGL, "Bone morphogenetic protein-2 release profile modulates bone formation in phosphorylated hydrogel", J Tissue Eng Regen Med, 12, pp.1339~1351 (2018)
  34. Fosse G, "Numerical density and distributional pattern of dentin tubules", Acta Odontol Scand, 50, pp.201~210 (1992)
  35. 김경욱, "Bone Induction by Demineralized Dentin Matrix in Nude Mouse Muscles", Maxillofacial Plastic Reconstructive Surgery, 36(2), pp.50~56 (2014), 대한악안면성형재건외과학회[DOI]
  36. Tanoue R, "Three-dimensional ultrastructural analysis of the interface between an implanted demineralised dentin matrix and the surrounding newly formed bone", Sci Rep, 8, pp.2858~ (2018)
  37. El Bialy I, "Formulation, delivery and stability of bone morphogenetic proteins for effective bone regeneration", Pharm Res, 34, pp.1152~1170 (2017)
  38. Rumpler M, "Osteoclasts on bone and dentin in vitro : mechanism of trail formation and comparison of resorption behavior", Calcif Tissue Int, 93, pp.526~539 (2013)

관련 논문AI추천

Demineralized dentin matrix combined with recombinant human bone morphogenetic protein-2 in rabbit calvarial defects김문영, 김영균, 류재준, 엄인웅, 장현석, 전상호, 황숙현대한구강악안면외과학회 · 대한구강악안면외과학회지2016 · 제42권 제2호Biochemical and histo-morphometrical analyses of bone and cartilage induced by human decalcified dentin matrix and BMP-2Junichi Hino, Junichi Tazaki, Katsutoshi Ito, Makoto Arisue, Masaru Murata, Toshiyuki Akazawa치의학연구원 · Oral Biology Research2011 · 제35권 제1호Comparative analysis of carrier systems for delivering bone morphogenetic proteins이중석, 임현창, 정의원, 정임희, 최성호대한치주과학회 · Journal of Periodontal & Implant Science2015 · 제45권 제4호Recombinant human bone morphogenetic protein-2와 2가지 scaffold를 이용한 골이식술: 증례연구김영균치의학연구원 · Oral Biology Research2014 · 제38권 제2호Stepwise verification of bone regeneration using recombinant human bone morphogenetic protein-2 in rat fibula model김형준, 남정우대한구강악안면외과학회 · 대한구강악안면외과학회지2017 · 제43권 제6호Increased osteoinductivity and mineralization by minimal concentration of bone morphogenetic protein-2 loaded onto biphasic calcium phosphate in a rabbit sinus김재신, 이중석, 조규성, 차재국, 최성호대한치주과학회 · Journal of Periodontal & Implant Science2016 · 제46권 제5호

이 간행물의 다른 논문 (7건)