Efficacy of Octacalcium Phosphate and Octacalcium Phosphate/Gelatin Composite on the Repair of Critical-Sized Calvarial Defects in Rats
Abstract
Objectives: The healing of bone defects in the craniofacial region is an important clinical issue. We aimed to compare the effects of octacalcium phosphate (OCP) and the combination of OCP/gelatin (OCP/Gel) on calvarial bone regeneration in rats.
Materials and Methods: In this study, 72 male Sprague Dawley rats were randomly assigned to the OCP (n=24), OCP/Gel (n=24), and control groups (n=24). Lesions with a diameter of 9 mm were created in the parietal bone and were filled with 9-mg OCP and OCP/Gel disks. In the control group, no substance was implanted in the defect. Sampling was performed on days 10, 14, 21, and 28 after the implantation. After tissue processing, 5-µm sections were prepared and stained by hematoxylin and eosin (H&E) stain. The sections were studied, and the volume fraction of the newly formed bone was assessed by Kruskal-Wallis test at a significance level of 0.05.
Results: In the experimental groups, new bone formation was detected at the margins of the defects 10 days after the implantation. With the progression of the healing process, the newly formed bone covered greater areas of the defects and developed a more mature structure. In the control group, the defects were primarily filled with a dense connective tissue with small islands of new bone. The results of histomorphometric assessments showed that the volume of the newly formed bone in the experimental groups had a significant statistical difference with that in the control group (P<0.001).
Conclusions: The OCP/Gel composite can be useful in the healing process of calvarial bone defects.
- Harris JS, Bemenderfer TB, Wessel AR, Kacena MA. A review of mouse critical size defect models in weight bearing bones. Bone. 2013 Jul;55(1):241-7.
- Costa-Pinto AR, Reis RL, Neves NM. Scaffolds based bone tissue engineering: the role of chitosan. Tissue Eng Part B Rev. 2011 Oct;17(5):331-47.
- Dall'Agnol R, de Carvalho MB, Rapoport A, Galvão da Silva MA. Induction of osteogenesis by demineralized homologous and xenograft bone matrix. Acta Cir Bras. 2003 May-Jun;18(3):178-82.
- Sargolzaei-Aval F, Sobhani A, Arab MR, Sarani SA, Heydari MH. The Efficacy of Implant of Octacalcium Phosphate in Combination with Bone Matrix Gelatin on Bone Regeneration in Skull Defects in Rat. Iran J Med Sci. 2004 Sep;29(3):124-9.
- Constantz BR, Ison IC, Fulmer MT, Poser RD, Smith ST, VanWagoner M, et al. Skeletal repair by in situ formation of the mineral phase of bone. Science. 1995 Mar 24;267(5205):1796-9.
- Pinholt EM, Ruyter IE, Haanaes HR, Bang G. Chemical, physical, and histologic studies on four commercial apatites used for alveolar ridge augmentation. J Oral Maxillofac Surg. 1992 Aug;50(8):859-67.
- Alper G, Bernick S, Yazdi M, Nimni ME. Osteogenesis in bone defects in rats: the effects of hydroxyapatite and demineralized bone matrix. Am J Med Sci. 1989 Dec;298(6):371-6.
- Ono I, Gunji H, Suda K, Kaneko F, Murata M, Saito T, et al. Bone induction of hydroxyapatite combined with bone morphogenetic protein and covered with periosteum. Plast Reconstr Surg. 1995 Jun;95(7):1265-72.
- Suzuki O, Nakamura M, Miyasaka Y, Kagayama M, Sakurai M. Maclura pomifera agglutinin-binding glycoconjugates on converted apatite from synthetic octacalcium phosphate implanted into subperiosteal region of mouse calvaria. Bone Miner. 1993 Feb;20(2):151-66.
- Sasano Y, Kamakura S, Nakamura M, Suzuki O, Mizoguchi I, Akita H, et al. Subperiosteal implantation of octacalcium phosphate (OCP) stimulates both chondrogenesis and osteogenesis in the tibia, but only osteogenesis in the parietal bone of a rat. Anat Rec. 1995 May;242(1):40-6.
- Bucholz RW. Nonallograft osteoconductive bone graft substitutes. Clin Orthop Relat Res. 2002 Feb;(395):44-52.
- LeGeros RZ. Properties of osteoconductive biomaterials: calcium phosphates. Clin Orthop Relat Res. 2002 Feb;(395):81-98.
- Dekker RJ, de Bruijn JD, Stigter M, Barrere F, Layrolle P, van Blitterswijk CA. Bone tissue engineering on amorphous carbonated apatite and crystalline octacalcium phosphate-coated titanium discs. Biomaterials. 2005 Sep;26(25):5231-9.
- Imaizumi H, Sakurai M, Kashimoto O, Kikawa T, Suzuki O. Comparative study on osteoconductivity by synthetic octacalcium phosphate and sintered hydroxyapatite in rabbit bone marrow. Calcif Tissue Int. 2006 Jan;78(1):45-54.
- Kamakura S, Sasano Y, Homma-Ohki H, Nakamura M, Suzuki O, Kagayama M, et al. Multinucleated giant cells recruited by implantation of octacalcium phosphate (OCP) in rat bone marrow share ultrastructural characteristics with osteoclasts. J Electron Microsc (Tokyo). 1997;46(5):397-403.
- Murakami Y, Honda Y, Anada T, Shimauchi H, Suzuki O. Comparative study on bone regeneration by synthetic octacalcium phosphate with various granule sizes. Acta Biomater. 2010 Apr;6(4):1542-8.
- Tanuma Y, Anada T, Honda Y, Kawai T, Kamakura S, Echigo S, et al. Granule size-dependent bone regenerative capacity of octacalcium phosphate in collagen matrix. Tissue Eng Part A. 2012 Mar;18(5-6):546-57.
- Handa T, Anada T, Honda Y, Yamazaki H, Kobayashi K, Kanda N, et al. The effect of an octacalcium phosphate co-precipitated gelatin composite on the repair of critical-sized rat calvarial defects. Acta Biomater. 2012 Mar; 8(3):1190-1200.
- Matsuno T, Omata K, Hashimoto Y, Tabata Y, Satoh T. Alveolar bone tissue engineering using composite scaffolds for drug delivery Jpn Dent Sci Rev. 2010 Aug;46(2):188-192.
- Ezoe Y, Anada T, Yamazaki H, Handa T, Kobayashi K, Takahashi T, et al. Characterization of partially hydrolyzed OCP crystals deposited in a gelatin matrix as a scaffold for bone tissue engineering. J Nanopart Res. 2015 Mar;17:127.
- Miura K, Anada T, Honda Y, Shiwaku Y, Kawai T, Echigo S, et al. Characterization and bioactivity of nano-submicro octacalcium phosphate/gelatin composite. Appl Surf Sci. 2013 Oct;282:138-145.
- Tanuma Y, Matsui K, Kawai T, Matsui A, Suzuki O, Kamakura S, et al. Comparison of bone regeneration between octacalcium phosphate/collagen composite and ß-tricalcium phosphate in canine calvarial defect. Oral Surg Oral Med Oral Pathol Oral Radiol. 2013 Jan;115(1):9-17.
- Liu X, Smith LA, Hu J, Ma PX. Biomimetic nanofibrous gelatin/apatite composite scaffolds for bone tissue engineering. Biomaterials. 2009 Apr;30(12):2252-8.
- Vyalikh A, Simon P, Kollmann T, Kniep R, Scheler U. Local environment in biomimetic hydroxyapatite-gelatin nanocomposites as probed by NMR spectroscopy. J Phys Chem C. 2011 Jan;115(5):1513-9.
- Zhang L, Jiang Y, Shi J, Sun X, Li J, Jiang Z. Biomimetic polymer-inorganic hybrid microcapsules for yeast alcohol dehydrogenase encapsulation. React Funct Polym. 2008 Nov;68(11):1507-15.
- Saito K, Anada T, Shiwaku Y, Chiba S, Miyatake N, Suzuki k, et al. Dose-dependent enhancement of octacalcium phosphate biodegradation with a gelatin matrix during bone regeneration in a rabbit tibial defect model. RSC Adv. 2016 Jul;69:64165-64174.
- Saberi EA, Sargolzaei-Aval F, Arab MR, Sargolzaei N, Shahraki H, Sargolzaei-Aval F. Bone regeneration by octacalcium phosphate (OCP)-gelatin composites in rat mandibular bone defects - a qualitative study. Adv Biores. 2017 Jan;8(1):17-24.
- Matsui A, Matsui K, Handa T, Tanuma Y, Miura K, Kato Y, et al. The regenerated bone quality by implantation of octacalcium phosphate collagen composites in a canine alveolar cleft model. Cleft Palate Craniofac J. 2014 Jul;51(4):420-30.
- Kanda N, Matsui K, Kawai T, Edamatsu H, Tanuma Y, Suzuki O, et al. Implantation of octacalcium phosphate collagen composites (OCP/Col) after extraction of canine deciduous teeth achieved undisturbed permanent tooth eruption. Arch Oral Biol. 2016 Dec;72:179-186.
- Kawai T, Suzuki O, Matsui K, Tanuma Y, Takahashi T, Kamakura S. Octacalcium phosphate collagen composite facilitates bone regeneration of large mandibular bone defect in humans. J Tissue Eng Regen Med. 2017 May;11(5):1641-1647.
- LeGeros RZ. Preparation of octacalcium phosphate (OCP): a direct fast method. Calcif Tissue Int. 1985 Mar;37(2):194-7.
- Suzuki O, Nakamura M, Miyasaka Y, Kagayama M, Sakurai M. Bone formation on synthetic precursors of hydroxyapatite. Tohoku J Exp Med. 1991 May;164(1):37-50.
- Suzuki O, Yagishita H, Amano T, Aoba T. Reversible structural changes of octacalcium phosphate and labile acid phosphate. J Dent Res. 1995 Nov;74(11):1764-9.
- Kim JH, Kim HW. Rat Defect Models for Bone Grafts and Tissue Engineered Bone Constructs. Tissue Eng and Regen Med. 2013 Dec;10(6):310-316.
- Kamakura S, Sasano Y, Homma H, Suzuki O, Kagayama M, Motegi K. Implantation of octacalcium phosphate (OCP) in rat skull defects enhances bone repair. J Dent Res. 1999 Nov;78(11):1682-7.
- Rabie AB, Deng YM, Samman N, Hägg U. The effect of demineralized bone matrix on the healing of intramembranous bone grafts in rabbit skull defects. J Dent Res. 1996 Apr;75(4):1045-51.
- Mulliken JB, Glowacki J. Induced osteogenesis for repair and construction in the craniofacial region. Plast Reconstr Surg. 1980 May;65(5):553-60.
- Suzuki O, Imaizumi H, Kamakura S, Katagiri T. Bone regeneration by synthetic octacalcium phosphate and its role in biological mineralization. Curr Med Chem. 2008;15(3):305-13.
- Habraken WJ, Wolke JG, Mikos AG, Jansen JA. Porcine gelatin microsphere/calcium phosphate cement composites: an in vitro degradation study. J Biomed Mater Res B Appl Biomater. 2009 Nov;91(2):555-61.
- Anada T, Kumagai T, Honda Y, Masuda T, Kamijo R, Kamakura S, et al. Dose-dependent osteogenic effect of octacalcium phosphate on mouse bone marrow stromal cells. Tissue Eng Part A. 2008 Jun;14(6):965-78.
- Kamakura S, Sasano Y, Nakajo S, Shimizu T, Suzuki O, Katou F, et al. Implantation of octacalcium phosphate combined with transforming growth factor-β1 Enhances bone repair as well as resorption of the implant in rat skull defects. J Biomed Mater Res. 2001 Nov;57(2):175-82.
- Takagi K, Urist MR. The reaction of the dura to bone morphogenetic protein (BMP) in repair of skull
defects. Ann Surg. 1982 Jul;196(1):100-109.
- Suzuki K, Honda Y, Anada T, Handa T, Miyatake N, Takahashi A, et al. Stimulatory capacity of an octacalcium phosphate/gelatin composite on bone regeneration in a rabbit tibia defect model. Phosphorus Res Bull. 2012 Sep;26:53-58.
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Issue | Vol 15, No 2 (2018) | |
Section | Original Article | |
Keywords | ||
Octacalcium Phosphate Gelatin Bone Regeneration Parietal Bone Rats |
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