A STUDY OF THE EFFECTS OF SEVERAL BONE-ENHANCING AGENTS

수종 골형성 증진재의 골형성능에 관한 조직형태계측학적 연구

  • Shin, Min-Cheol (Department of Oral and Maxillofacial Surgery, College of Dentistry, Kyung-Hee University) ;
  • Ryu, Dong-Mok (Department of Oral and Maxillofacial Surgery, College of Dentistry, Kyung-Hee University)
  • 신민철 (경희대학교 치과대학 구강악안면외과학교실) ;
  • 류동목 (경희대학교 치과대학 구강악안면외과학교실)
  • Published : 2003.10.30

Abstract

Several agents are in use to promote new bone formation during bone graft procedures in maxillofacial region. Among them, we have used crude BMP, PRP, and P-15 for experimentally created defects with accompanying graft materials in the rabbit model. The aim of this study is to analyze the effect of above mentioned agents on bone formation using histologic and histomorphometrical methods, thus to provide experimental support for clinical application of these agents. Six rabbits were used as experimental animals. Four surgical defects were created on the distal femoral heads of each animal using trephine drill. The defects were filled with each agents with accompaning graft materials as experimental groups and particulate corti-co-cancellous autogenous graft as control. For histomorphometric analysis, fluorescent dye was injected at 2week and 1week before sacrifice. Then, the animals were sacrificed at 2, 4 and 8weeks after surgery and histologic and histomorphometric examinations were achieved. At two weeks after bone graft, bone formation and active remodeling process were examined in all experimental groups and the control. But the intensity of such activities of the experiments were somewhat weaker than that of the control. In BMP group, the amount of newly formed osteoid was increased constantly and the amount was preserved constantly in PRP group. But in P-15 group, the amount of newly formed osteoid was decreased with time to 8week after surgery. Histologic findings showed superior bony quantity and quality in PRP group than that of P-15 group. MAR(Mineralization Apposition Rate) of all experimental groups were slower than that of control group. In P-15 group, constant foreign body reaction was observed at all periods and the graft material showed inwardly destroyed characteristics rather to mature. The data from this study provide the basis for future studies for evaluating the long-term remodeling process and foreign body reactions observed in P-15 group and clinical study for predictable use of these agents.

Keywords

References

  1. Urist MR: Bone: Formation by autoinduction. Science 150:893-899, 1965
  2. Urist MR, Iwata H, Ceccotti PL et al: Bone morphogenesis in implants of insoluble bone gelatin(cell differentiation/osteogenesis/ noncollagenous proteins). Proc Nat Acad Sci USA 70:3511-3515, 1973. https://doi.org/10.1073/pnas.70.12.3511
  3. Urist MR, Mikulski A, Lietze A: Solubilized and insolubilized bone morphogenetic protein(cell differentiation/osteogenesis/noncollagenous protein). Proc Nat Acad Sci USA 76:1828-1832, 1979. https://doi.org/10.1073/pnas.76.4.1828
  4. Wozney JM, Rosen V, Celeste AJ et al: Novel regulators of bone formation; molecular clones and activities. Science 242:1528-1534, 1988
  5. Wang EA, Rosen V, Cordes P et al: Purification and characterization of other distinct bone-inducing factors(bone morphogenetic protein/ bone formation). Proc Nat Acad Sci USA 85:9484-9488, 1988. https://doi.org/10.1073/pnas.85.24.9484
  6. Toriumi DM, Kotler HS, Luxenberg DP et al: Mandibular reconstruction with a recombinant bone-inducing factor; functional, histologic, and biomechanical evaluation. Arch Otolaryngol Head Neck Surg 117:1101-1112, 1991. https://doi.org/10.1001/archotol.1991.01870220049009
  7. Li XJ, Toriumi DM, Turek TJ et al: Healing of a canine critical-sized defect with an rhBMP-2/collagen implant involves de nove bone formation without chondrogenesis. J Bone Miner Res 11:S379, 1996.
  8. Howell TH, Fiorellini J, Jones A et al: A feasibility study evaluating rhBMP-2/absorbable collagen sponge device for local alveolar ridge preservation or augmentation. Int J Periodont Rest Dent 17:125-139, 1997.
  9. Boyne PJ, Marx RE, Nevins M et al: A feasibility study evaluating rhBMP-2/absorbable collagen sponge for maxillary sinus floor augmentation. Int J Periodont Rest Dent 17:11-25, 1997.
  10. 조병도, 허익, 박준봉, 이만섭, 권영혁: 혈소판유래성장인자와 상피성장인자가 치주인대세포와 골수세포의 성장에 미치는 영향. 경희치대논문집 18:189-207, 1996.
  11. 이석재, 신제원: Platelet-derived growth factor와 insulin-like growth factor-I 이 치주인대 섬유모세포에 미치는 영향에 관한 연구. 대한구강해부학회지 20:127-139, 1996.
  12. 김현호, 이상철: 수종의 성장인자가 초기 골치유과정에 미치는 영향에 관한 연구. 대한구강악안면외과학회지 23:581-596, 1997.
  13. 박상일, 정진형, 임성빈, 김정근: 혈소판 농축혈장이 조골세포의 초기부착과 증식 및 활성에 미치는 생물학적 영향. 대한치주과학회지 31:513-528, 2001.
  14. Landeberg R, Roy M, Glickman RS: Quantification of growth factor levels using a simplified method of platelet-rich plasma gel preparation. J Oral Maxillofac Surg 58:297-300, 2000. https://doi.org/10.1016/S0278-2391(00)90058-2
  15. 오지수, 정진형, 임성빈: 2급 치근이개부 치료시 합성골 이식 및 혈소판농축혈장의 골재생효과에 대한 디지털 공제술의 정량적분석. 대한치주과학회지 31:465-474, 2001.
  16. Wittkampf ARM: Augmentation of the maxillary alveolar ridge with hydroxyapatite and fibrin glue. J Oral Maxillofac Surg 46:1019-1021, 1988. https://doi.org/10.1016/0278-2391(88)90344-8
  17. Hotz G: Alveolar ridge augmentation with hydroxylapatite using fibrin sealant for fixation. Part II: Clinical application. Int J Oral Maxillofac Surg 20:208-213, 1991. https://doi.org/10.1016/S0901-5027(05)80176-6
  18. Whitman DH, Berry RL, Green DM: Platelet gel; an autologous alternative to fibrin glue with application in oral and maxillofacial surgery. J Oral Maxillofac Surg 55:1294-1299, 1997. https://doi.org/10.1016/S0278-2391(97)90187-7
  19. Marx RE, Carlson ER, Eichstaedt RM et al: Platelet-rich plasma; growth factor enhancement for bone grafts. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 85:638-646, 1998. https://doi.org/10.1016/S1079-2104(98)90029-4
  20. Tayapongsak P, O’Brien D, Monteiro CB et al: Autologous fibrin adhesive in mandibular reconstruction with particulate cancellous bone and marrow. J Oral Maxillofac Surg 52:161-165, 1994. https://doi.org/10.1016/0278-2391(94)90401-4
  21. Bhatnagar RS, Qian JJ, Wedrychowska A et al: Construction of biomimetic environments with a synthetic peptide analogue of collagen. Mat Res Soc Symp Proc 530:43-54, 1998. https://doi.org/10.1557/PROC-530-43
  22. Bhatnagar RS, Qian JJ, Wedrychowska A et al: Biomimetic habitat for cells; ordered matrix deposition and differentiation in gingival fibroblasts cultured on hydroxyapatite coated with a collagen analogue. Cells Mater 9:93-104, 1999.
  23. Hay ED: Extracellular matrix, cell skeletons, and embryonic development. Am J Med Genetic 34:14-29, 1989. https://doi.org/10.1002/ajmg.1320340107
  24. Bhatnagar RS, Qian JJ, Wedrychowska A et al: Design of biomimetic habitats for tissue engineering with P-15, a synthetic peptide analogue of collagen. Tissue Engineering 5:53-65, 1999. https://doi.org/10.1089/ten.1999.5.53
  25. Qian JJ, Bhatnagar RS: Enhanced cell attachment to anorganic bone mineral in the presence of a synthetic peptide related to collagen. J Biomed Mat Res 31:545-554, 1996. https://doi.org/10.1002/(SICI)1097-4636(199608)31:4<545::AID-JBM15>3.0.CO;2-F
  26. Yukna RA, Callan DP, Krauser JT et al: Multi-center clinical evaluation of combination anorganic bovine-derived hydroxyapatite matrix(ABM)/cell binding peptide(P-15) as a bone replacement graft material in human periodontal osseous defects; 6-month results. J Periodontol 69:655-663, 1998. https://doi.org/10.1902/jop.1998.69.6.655
  27. Yukna RA, Krauser JT, Callan DP et al: Multi-center clinical comparison of combination anorganic bovine-derived hydroxyapatite matrix(ABM)/cell binding peptide(P-15) and ABM in human periodontal osseous defects; 6-month result. J Periodontol 71:1671-1679, 2000. https://doi.org/10.1902/jop.2000.71.11.1671
  28. Yukna RA, Krauser JT, Callan DP et al: Thirty-six month follow up of 25 patients treated with combination anorganic bovine-derived hydroxyapatite matrix(ABM)/cell-binding peptide(P-15) bone replacement grafts in human infrabony defects: I. Clinical findings. J Periodontol 73:123-128, 2002. https://doi.org/10.1902/jop.2002.73.1.123
  29. Krauser JT, Rohrer MD, Wallace SS: Human histologic and histomorphometric analysis comparing Osteograf/N with PepGen P-15 in the maxillary sinus elevation procedure; a case report. Imp Dentistry 9:298-302, 2000. https://doi.org/10.1097/00008505-200009040-00004
  30. Misch CE, Dietsh F: Bone-grafting materials in implant dentistry. Implant Dent 2:158-167, 1993. https://doi.org/10.1097/00008505-199309000-00003
  31. Kale AA, Di Cesare PE: Osteoinductive agents; basic science and clinical applications. Am J Orthop 24:752-761, 1995
  32. Stevenson S: Enhancement of fracture healing with autogenous and allogenic bone grafts. Clin Orthop Rel Res 355S:239-246, 1998. https://doi.org/10.1097/00003086-199810001-00024
  33. Garg AK: Grafting materials in repair and restoration. In: Lynch SE, Genco RJ, Marx RE eds. Tissue Engineering. 1st ed, Quintessence Publishing Co., Chicago, IL 1999.
  34. Celeste AJ, Iannazzi JA, Taylor RC et al: Identification of transforming growth factor$\beta$ family members present in bone-inductive protein purified from bovine bone. Proc Natl Acad Sci USA 87:9843-9847, 1990. https://doi.org/10.1073/pnas.87.24.9843
  35. Ozkaynak E, Schnegelsberg PN, Jin DF et al: Osteogenic protein-2; a new member of transforming growth factor-beta superfamily expressed in early embryogenesis. J Biol Chem 267:25220-25227, 1992.
  36. Celeste AJ, Song JJ, Cox K et al: Bone morphogenetic protein-9, a new member of the TGF-beta superfamily. J Bone Miner Res 9(suppl): S136, 1994.
  37. Wang EA, Rosen V, D’Alessandro JS et al: Recombinant human bone morphogenetic protein induces bone formation(cartilage induction). Proc Nat Acad Sci USA 87:2220-2224, 1990. https://doi.org/10.1073/pnas.87.6.2220
  38. Matras H: The use of fibrin sealant in oral and maxillofacial surgery. J Oral Maxillofac Surg 40:617-622, 1982. https://doi.org/10.1016/0278-2391(82)90108-2
  39. Wepner F, Fries R, Platz H: The use of fibrin adhesion system for local hemostasis in oral surgery. J Oral Maxillofac Surg 40:555-558, 1982. https://doi.org/10.1016/0278-2391(82)90282-8
  40. Matras H: Fibrin seal; the state of the art. J Oral Maxillofac Surg 43:605-611, 1985. https://doi.org/10.1016/0278-2391(85)90129-6
  41. 허원실, 이상철: Butyl-Cyanoacrylate(Histoacryl�)와 Fibrin sealant(Tisseel�)를 이용한 피부이식시 조직치유에 관한 실험적 연구. 대한구강악안면외과학회지 16:113-123, 1990.
  42. 하정완, 김수관, 조세인등: 혈소판 풍부혈장의 임상적 응용. 대한악안면성형재건외과학회지 23:452-457, 2001.
  43. Greenlagh DG: The role of growth factors in wound healing. J Trauma 41:159-167, 1996. https://doi.org/10.1097/00005373-199607000-00029
  44. Ross R, Raines EW, Bowen-Pope DF: The biology of platelet derived growth factor. Cell 46:155-169, 1986. https://doi.org/10.1016/0092-8674(86)90733-6
  45. Antonides HN, Williams LT: Human platelet-derived growth factor; structure and functions. Federation Proceedings 42:2630-2634, 1983.
  46. 이상철: 골결손부에 Natural bone minerals(Pyrost�)의 골형성 유도에 관한 실험적 연구; 성장인자의 효과비교. 경희치대논문집 13:823-830, 1991.
  47. Pierce GF, Vande Berg J, Rudolph R et al: Platelet-derived growth factor-BB and transforming growth factor beta1 selectively modulate glycosaminoglycans, collagen, and myofibroblasts in excisional wounds. Am J Pathol 138:629-646, 1991.
  48. Beck LS, DeGuzman L, Lee WP: One systemic administration of transforming growth factor-beta reverses age or glucocorticoidimpaired wound healing. J Clin Invest 93:2841-2849, 1993.
  49. Mohan S, Baylink DJ: Bone growth factor. Clin Orthop Rel Res 263:30-43, 1991.
  50. Szabo G, Suba Z, Hrabak K et al: Autogenous bone versus $\beta$-tricalcium phosphate graft alone for bilateral sinus elevations(2-and 3- dimensional computed tomographic, histologic, and histomorphometric evaluations); preliminary results. Int J Oral Maxillofac Imp 16:681-692, 2001.
  51. Merten HA, Wiltfang J, Grohmann U et al: Intraindivisual comparative animal study of $\alpha$- and $\beta$-tricalcium phosphate degradation in conjunction with simultaneous insertion of dental implants. J Craniofac Surg 12:59-68, 2001. https://doi.org/10.1097/00001665-200101000-00010
  52. Bhatnagar RS, Qian JJ, Gough CA: The role in cell binding of a $\beta$-bend within the triple helical region in collagen $\alpha$1(I)chain; structural and biological evidence for conformational tautomerism on fiber surface. J Biomol Struct Dynamics 14:547-560, 1997. https://doi.org/10.1080/07391102.1997.10508155
  53. Scaria PV, Sorensen KR, Bhatnagar RS: Expression of a reactive molecular perspective within the triple helical region of collagen. Am Peptide Symp 11:605, 1989.
  54. Ingber DE, Folkman J: Mechanical switching between growth and differentiation during fibroblast growth factor-stimulated angiogenesis in vitro. J Cell Biol 109:317-330, 1989. https://doi.org/10.1083/jcb.109.1.317
  55. Watson PA: Function follows form; generation of intracellular signals by cell deformation. FASEB J 5:2013-2019, 1991. https://doi.org/10.1096/fasebj.5.7.1707019
  56. Lallier TE, Yukna RA, Marie S et al: The putative collagen binding peptide hastens periodontal ligament cell attachment to bone replacement graft materials. J Periodontol 72:990-997, 2001. https://doi.org/10.1902/jop.2001.72.8.990
  57. Inoue N, Larsson S, Kim W et al: Bone histomorphometric respons es under dynamic loading. Trans Orthop Res Soc 19:204-215, 1994.