{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T21:51:25Z","timestamp":1777585885756,"version":"3.51.4"},"reference-count":51,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2019,12,2]],"date-time":"2019-12-02T00:00:00Z","timestamp":1575244800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP19im0502004"],"award-info":[{"award-number":["JP19im0502004"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Materials"],"abstract":"<jats:p>The utility of carbonate apatite (CO3Ap) as a bone substitute has been demonstrated. The feasibility of fabricating macroporous CO3Ap was evaluated through a two-step dissolution\u2013precipitation reaction using gypsum as the precursor and spherical phenol resin as the porogen. Porogen-containing gypsum was heated to burn out the porogen and to fabricate macroporous structures. Gypsum transformed into CaCO3 upon immersion in a sodium carbonate solution, while maintaining its macroporous structure. Next, CaCO3 transformed into CO3Ap upon immersion in a Na2HPO4 solution while maintaining its macroporous structure. The utility of the macroporous CO3Ap for histologically reconstructing bone defects was evaluated in rabbit femurs. After 4 weeks, a much larger bone was formed inside the macroporous CO3Ap than that inside non-macroporous CO3Ap and macroporous hydroxyapatite (HAp). A larger amount of bone was observed inside non-macroporous CO3Ap than inside macroporous HAp. The bone defects were completely reconstructed within 12 weeks using macroporous CO3Ap. In conclusion, macroporous CO3Ap has good potential as an ideal bone substitute.<\/jats:p>","DOI":"10.3390\/ma12233997","type":"journal-article","created":{"date-parts":[[2019,12,3]],"date-time":"2019-12-03T04:58:39Z","timestamp":1575349119000},"page":"3997","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Fabrication and Histological Evaluation of Porous Carbonate Apatite Block from Gypsum Block Containing Spherical Phenol Resin as a Porogen"],"prefix":"10.3390","volume":"12","author":[{"given":"Yuta","family":"Sakemi","sequence":"first","affiliation":[{"name":"Department of Orthopedic Surgery, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Koichiro","family":"Hayashi","sequence":"additional","affiliation":[{"name":"Department of Biomaterials, Faculty of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akira","family":"Tsuchiya","sequence":"additional","affiliation":[{"name":"Department of Biomaterials, Faculty of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasuharu","family":"Nakashima","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kunio","family":"Ishikawa","sequence":"additional","affiliation":[{"name":"Department of Biomaterials, Faculty of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,12,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1046\/j.1440-1622.2001.02128.x","article-title":"Synthetic bone graft substitutes","volume":"71","author":"Moore","year":"2001","journal-title":"ANZ J. Surg."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1002\/(SICI)1097-4636(199824)43:4<380::AID-JBM6>3.0.CO;2-D","article-title":"Principles of tissue engineering applied to programmable osteogenesis","volume":"43","author":"Brekke","year":"1998","journal-title":"J. Biomed. Mater. Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1111\/j.1600-0757.1999.tb00148.x","article-title":"Bone and bone substitutes","volume":"19","author":"Nasr","year":"1999","journal-title":"Periodontol. 2000"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1324","DOI":"10.1097\/00007632-198912000-00009","article-title":"Harvesting autogenous iliac bone grafts: A review of complications and techniques","volume":"14","author":"Kurz","year":"1989","journal-title":"Spine"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1302\/0301-620X.72B2.2155908","article-title":"The use of calcium hydroxyapatite ceramic in bone tumour surgery","volume":"72","author":"Uchida","year":"1990","journal-title":"J. Bone Joint Surg."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1007\/BF02013723","article-title":"Hydrazine-deproteinated bone mineral","volume":"12","author":"Termine","year":"1973","journal-title":"Phys. Chem. Prop. Calcif. Tissue Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1002\/(SICI)1097-4636(19980315)39:4<603::AID-JBM15>3.0.CO;2-7","article-title":"Sintered carbonate apatites as bioresorbable bone substitutes","volume":"39","author":"Doi","year":"1998","journal-title":"J. Biomed. Mater. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.1126\/science.155.3768.1409","article-title":"Apatite crystallites: Effects of carbonate on morphology","volume":"155","author":"Legeros","year":"1967","journal-title":"Science"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1138","DOI":"10.3390\/ma3021138","article-title":"Bone substitute fabrication based on dissolution-precipitation reaction","volume":"3","author":"Ishikawa","year":"2010","journal-title":"Materials"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"341","DOI":"10.2109\/jcersj2.118.341","article-title":"Fabrication of low crystalline B-type carbonate apatite block from low crystalline calcite block","volume":"118","author":"Ishikawa","year":"2010","journal-title":"J. Ceram. Soc. Jpn."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"7843","DOI":"10.1007\/s10853-007-1629-3","article-title":"Characterization of macroporous carbonate-substituted hydroxyapatite bodies prepared in different phosphate solutions","volume":"42","author":"Lee","year":"2007","journal-title":"J. Mater. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"710","DOI":"10.4012\/dmj.27.710","article-title":"Fabrication of B-type carbonate apatite blocks by the phosphorylation of free-molding gypsum-calcite composite","volume":"27","author":"Zaman","year":"2008","journal-title":"Dent Mater. J."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"303","DOI":"10.4012\/dmj.2009-095","article-title":"Fabrication of carbonate apatite block based on internal dissolution-precipitation reaction of dicalcium phosphate and calcium carbonate","volume":"29","author":"Daitou","year":"2010","journal-title":"Dent Mater. J."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"14","DOI":"10.4012\/dmj.2010-087","article-title":"Fabrication of low-crystalline carbonate apatite foam bone replacement based on phase transformation of calcite foam","volume":"30","author":"Maruta","year":"2011","journal-title":"Dent Mater. J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"549","DOI":"10.4012\/dmj.2011-253","article-title":"Fabrication of solid and hollow carbonate apatite microspheres as bone substitutes using calcite microspheres as a precursor","volume":"31","author":"Sunouchi","year":"2012","journal-title":"Dent. Mater. J."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1014","DOI":"10.1002\/jbm.a.36640","article-title":"Fabrication of carbonate apatite honeycomb and its tissue response","volume":"107A","author":"Ishikawa","year":"2019","journal-title":"J. Biomed. Mater. Res. Part. A"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Tsuru, K., Kanazawa, M., Yoshimoto, A., Nakashima, Y., and Ishikawa, K. (2017). Fabrication of carbonate apatite block through a dissolution\u2013precipitation reaction using calcium hydrogen phosphate dihydrate block as a precursor. Materials, 10.","DOI":"10.3390\/ma10040374"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1007\/s10856-017-5896-5","article-title":"Evaluation of carbonate apatite blocks fabricated from dicalcium phosphate dihydrate blocks for reconstruction of rabbit femoral and tibial defects","volume":"28","author":"Kanazawa","year":"2017","journal-title":"J. Mater. Sci. Mater. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1002\/jbm.a.31620","article-title":"Fabrication of macroporous carbonate apatite foam by hydrothermal conversion of \u03b1-tricalcium phosphate in carbonate solutions","volume":"87","author":"Wakae","year":"2008","journal-title":"J. Biomed. Mater. Res. A."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"205","DOI":"10.3233\/BME-2009-0581","article-title":"Effect of temperature on crystallinity of carbonate apatite foam prepared from alpha-tricalcium phosphate by hydrothermal treatment","volume":"19","author":"Takeuchi","year":"2009","journal-title":"Bio-Med. Mater. Eng."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1002\/jbm.a.31904","article-title":"Fabrication of low-crystallinity hydroxyapatite foam based on the setting reaction of alpha-tricalcium phosphate foam","volume":"88","author":"Karashima","year":"2009","journal-title":"J. Biomed. Mater. Res. A"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/j.ceramint.2015.08.081","article-title":"Fabrication of carbonate apatite foam based on the setting reaction of \u03b1-tricalcium phosphate foam granules","volume":"42","author":"Sugiura","year":"2016","journal-title":"Ceram. Int."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"11149","DOI":"10.1016\/j.ceramint.2017.05.162","article-title":"Fabrication of interconnected porous calcium-deficient hydroxyapatite using the setting reaction of \u03b1 tricalcium phosphate spherical granules","volume":"43","author":"Arifta","year":"2017","journal-title":"Cerams Int."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1002\/jbm.b.34117","article-title":"Fabrication and evaluation of interconnected porous carbonate apatite from alpha tricalcium phosphate spheres","volume":"107","author":"Ishikawa","year":"2019","journal-title":"J. Biomed. Mater. Res. Part. B Appl. Biomater."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1002\/jbm.b.30609","article-title":"Transformation of 3DP gypsum model to HA by treating in ammonium phosphate solution","volume":"80B","author":"Lowmunkong","year":"2007","journal-title":"J. Biomed. Mater. Res. Part B App. Biomater."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1002\/jbm.b.31314","article-title":"Fabrication of freeform bone-filling calcium phosphate ceramics by gypsum 3D printing method","volume":"90","author":"Lowmunkong","year":"2009","journal-title":"J. Biomed. Mater. Res. B Appl. Biomater."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"166","DOI":"10.4012\/dmj.2013-192","article-title":"Fabrication of carbonate apatite block from set gypsum based on dissolution-precipitation reaction in phosphate-carbonate mixed solution","volume":"33","author":"Nomura","year":"2014","journal-title":"Dent. Mater. J."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"579541","DOI":"10.1155\/2015\/579541","article-title":"Histological comparison in rats between carbonate apatite fabricated from gypsum and sintered hydroxyapatite on bone remodeling","volume":"2015","author":"Ayukawa","year":"2015","journal-title":"BioMed Res. Int."},{"key":"ref_29","unstructured":"Antoniac, I. (2018). Carbonate apatite bone replacement. Handbook of Bioceeramics and Biocomposite, Springer."},{"key":"ref_30","unstructured":"Khang, G. (2017). Carbonate apatite scaffold for regenerative medicine. Handbook of Intelligent Scaffold for Tissue Engineering and Regenerative Medicine, Pan Stanford Publishing. [2nd ed.]."},{"key":"ref_31","unstructured":"Ishikawa, K. Carbonate apatite bone replacement: Learn from the bone. J. Ceramic Soc. Jpn., in press."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1007\/s10856-015-5431-5","article-title":"Miyamoto Y: Effects of low crystalline carbonate apatite on proliferation and osteoblastic differentiation of human bone marrow cells","volume":"26","author":"Nagai","year":"2015","journal-title":"J. Mater. Sci. Mater. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3540","DOI":"10.1016\/j.ceramint.2016.11.156","article-title":"The effect of macro\/micro combination pore structure of biphasic calcium phosphate scaffold on bioactivity","volume":"43","author":"You","year":"2016","journal-title":"Ceram. Int."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"10928","DOI":"10.1039\/C5NR09149G","article-title":"Hierarchical TiO\/C nanocomposite monoliths with a robust scaffolding architecture, mesopore-macropore network and TiO-C heterostructure for high-performance lithium ion batteries","volume":"8","author":"Huang","year":"2016","journal-title":"Nanoscale"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.biomaterials.2016.07.004","article-title":"Biologically and mechanically driven design of an RGD-mimetic macroporous foam for adipose tissue engineering applications","volume":"104","author":"Rossi","year":"2016","journal-title":"Biomaterials"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1007\/BF02556059","article-title":"The carbonate environment in bone mineral: A resolution-enhanced Fourier transform infrared spectroscopy study","volume":"45","author":"Rey","year":"1989","journal-title":"Calcif. Tissue Int."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1007\/BF02553704","article-title":"Infrared determination of the degree of substitution of hydroxyl bicarbonate ions in human dental enamel","volume":"37","author":"Elliott","year":"1985","journal-title":"Calcif. Tissue Int."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1016\/S0021-9290(98)00057-8","article-title":"Yield strain behavior of trabecular bone","volume":"31","author":"Kopperdahl","year":"1998","journal-title":"J. Biomech."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"S05","DOI":"10.2106\/00004623-200100002-00005","article-title":"Geometry of carriers controlling phenotypic expression in bmp-induced osteogenesis and chondrogenesis","volume":"83","author":"Kuboki","year":"2001","journal-title":"J. Bone Joint Surg. Am."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1097\/00003086-200202000-00009","article-title":"Properties of osteoconductive biomaterials: Calcium phosphates","volume":"395","author":"LeGeros","year":"2002","journal-title":"Clin. Orthop. Relat. Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1093\/oxfordjournals.jbchem.a021589","article-title":"Pore size of porous hydroxyapatite as the cell-substratum controls bmp-induced osteogenesis","volume":"121","author":"Tsuruga","year":"1997","journal-title":"J. Biochem."},{"key":"ref_42","first-page":"86","article-title":"Effect of the macroporosity for osseous substitution of calcium phosphate ceramics","volume":"11","author":"Daculsi","year":"1990","journal-title":"Biomaterials"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1002\/jor.1100030306","article-title":"Comparative study of porous hydroxyapatite and tricalcium phosphate as bone substitute","volume":"3","author":"Shimazaki","year":"1985","journal-title":"J. Orthop. Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1002\/jor.1100030108","article-title":"Bone ingrowth into three different porous ceramics implanted into the tibia of rats and rabbits","volume":"3","author":"Uchida","year":"1985","journal-title":"J. Orthop. Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.actbio.2015.01.034","article-title":"3D-printed hierarchical scaffold for localized isoniazid\/rifampin drug delivery and osteoarticular tuberculosis therapy","volume":"16","author":"Zhu","year":"2015","journal-title":"Acta Biomater."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/S1369-7021(08)70086-5","article-title":"Biomaterials for bone tissue engineering","volume":"11","author":"Stevens","year":"2008","journal-title":"Mater. Today"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2269","DOI":"10.1016\/j.actbio.2014.01.001","article-title":"Three-dimensional printing of strontium-containing mesoporous bioactive glass scaffolds for bone regeneration","volume":"10","author":"Zhang","year":"2014","journal-title":"Acta Biomater."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1177\/0954411916680236","article-title":"Three-dimensional printed bone scaffolds: The role of nano\/micro-hydroxyapatite particles on the adhesion and differentiation of human mesenchymal stem cells","volume":"231","author":"Domingos","year":"2017","journal-title":"Proc. Inst. Mech. Eng. Part. H J. Eng. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"3677","DOI":"10.1002\/jbm.a.35038","article-title":"Calcium phosphate scaffolds mimicking the gradient architecture of native long bones","volume":"102A","author":"Lindner","year":"2014","journal-title":"J. Biomed. Mater. Res. Part. A"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1002\/term.2362","article-title":"Development of a synthetic tissue engineered threedimensional printed bioceramic-based bone graft with homogenously distributed osteoblasts and mineralizing bone matrix in vitro","volume":"12","author":"Giacomini","year":"2018","journal-title":"J. Tissue Eng. Regen. Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1016\/j.colsurfb.2016.02.007","article-title":"Osteogenic effect of controlled released rhBMP-2 in 3D printed poroushydroxyapatite scaffold","volume":"141","author":"Wang","year":"2016","journal-title":"Colloids Surf. B Biointerfaces"}],"container-title":["Materials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1996-1944\/12\/23\/3997\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:39:18Z","timestamp":1760189958000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1996-1944\/12\/23\/3997"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12,2]]},"references-count":51,"journal-issue":{"issue":"23","published-online":{"date-parts":[[2019,12]]}},"alternative-id":["ma12233997"],"URL":"https:\/\/doi.org\/10.3390\/ma12233997","relation":{},"ISSN":["1996-1944"],"issn-type":[{"value":"1996-1944","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,12,2]]}}}