{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T14:16:34Z","timestamp":1788617794399,"version":"build-2803163510"},"reference-count":31,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2021,10,7]],"date-time":"2021-10-07T00:00:00Z","timestamp":1633564800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JSPS KAKENHI JP18F18106"],"award-info":[{"award-number":["JSPS KAKENHI JP18F18106"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Materials"],"abstract":"<jats:p>Surface-mineralized collagen sponges have attracted much attention as scaffolds for bone tissue engineering. Recently, we developed amorphous calcium phosphate (ACP) and low-crystalline apatite coating processes on collagen sponges. In the present study, we applied these coating processes to granular collagen sponges (referred to as Col) to compare the bone tissue regeneration capabilities of ACP-coated and apatite-coated Col (referred to as Col-ACP and Col-Ap, respectively) using a rat cranial bone defect model. According to micro-CT and histological analyses, Col-Ap enhanced bone tissue regeneration compared to Col, whereas Col-ACP did not. These results not only demonstrated the superior bone tissue regeneration capability of Col-Ap, but also indicated limitations of the in vitro simulated body fluid (SBF) test used in our previous study. Despite the apatite-forming ability of Col-ACP in SBF, it was ineffective in improving bone tissue regeneration in vivo, unlike Col-Ap, most likely due to the quick resorption of the ACP coating in the defect site. The present results clarified the importance of the coating stability in vivo and revealed that the low-crystalline apatite coating was more beneficial than the ACP coating in the fabrication of surface-mineralized collagen sponges for use as bone tissue engineering scaffolds.<\/jats:p>","DOI":"10.3390\/ma14195860","type":"journal-article","created":{"date-parts":[[2021,10,8]],"date-time":"2021-10-08T21:23:55Z","timestamp":1633728235000},"page":"5860","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Bone Tissue Regeneration by Collagen Scaffolds with Different Calcium Phosphate Coatings: Amorphous Calcium Phosphate and Low-Crystalline Apatite"],"prefix":"10.3390","volume":"14","author":[{"given":"Syama","family":"Santhakumar","sequence":"first","affiliation":[{"name":"Nanomaterials Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Central 5, 1-1-1 Higashi, Tsukuba, Ibaraki 305-8565, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6037-5558","authenticated-orcid":false,"given":"Ayako","family":"Oyane","sequence":"additional","affiliation":[{"name":"Nanomaterials Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Central 5, 1-1-1 Higashi, Tsukuba, Ibaraki 305-8565, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6759-3205","authenticated-orcid":false,"given":"Maki","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Nanomaterials Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Central 5, 1-1-1 Higashi, Tsukuba, Ibaraki 305-8565, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuto","family":"Yoshino","sequence":"additional","affiliation":[{"name":"Department of Periodontology and Endodontology, Faculty of Dental Medicine, Hokkaido University, N13W7, Kita-ku, Sapporo, Hokkaido 060-8586, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed Katib","family":"Alruwaili","sequence":"additional","affiliation":[{"name":"Department of Periodontology and Endodontology, Faculty of Dental Medicine, Hokkaido University, N13W7, Kita-ku, Sapporo, Hokkaido 060-8586, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1023-7680","authenticated-orcid":false,"given":"Hirofumi","family":"Miyaji","sequence":"additional","affiliation":[{"name":"Department of Periodontology and Endodontology, Faculty of Dental Medicine, Hokkaido University, N13W7, Kita-ku, Sapporo, Hokkaido 060-8586, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Weiss, L. (1983). The skeletal tissue. Histology, Cell and Tissue Biology, The MacMillan Press, Ltd.. [5th ed.].","DOI":"10.1007\/978-1-349-06859-3"},{"key":"ref_2","first-page":"25","article-title":"Bone tissue reaction of nano-hydroxyapatite\/collagen composite at the early stage of implantation","volume":"18","author":"Fukui","year":"2008","journal-title":"Biomed. Mater. Eng."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1659","DOI":"10.1163\/092050611X589419","article-title":"Efficient bone regeneration induced by bone morphogenetic protein-2 released from apatite-coated collagen scaffolds","volume":"23","author":"Yang","year":"2012","journal-title":"J. Biomater. Sci. Polym. Ed."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1226","DOI":"10.1016\/j.joen.2016.04.027","article-title":"Bioinspired collagen-apatite nanocomposites for bone regeneration","volume":"42","author":"Liu","year":"2016","journal-title":"J. Endod."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1007\/BF02010752","article-title":"A thermodynamic analysis of the amorphous to crystalline calcium phosphate transformation","volume":"25","author":"Meyer","year":"1978","journal-title":"Calcif. Tiss. Res."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Amjad, Z. (1998). Amorphous calcium phosphate: Thermodynamic and kinetic considerations. Calcium Phosphates in Biological and Industrial Systems, Springer.","DOI":"10.1007\/978-1-4615-5517-9"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"12748","DOI":"10.1073\/pnas.0803354105","article-title":"Amorphous calcium phosphate is a major component of the forming fin bones of zebrafish: Indications for an amorphous precursor phase","volume":"105","author":"Mahamid","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1016\/j.jsb.2011.03.014","article-title":"Bone mineralization proceeds through intracellular calcium phosphate loaded vesicles: A cryo-electron microscopy study","volume":"174","author":"Mahamid","year":"2011","journal-title":"J. Struct. Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"14170","DOI":"10.1073\/pnas.1208916109","article-title":"The role of intracellular calcium phosphate in osteoblast-mediated bone apatite formation","volume":"109","author":"Boonrungsiman","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1004","DOI":"10.1038\/nmat2875","article-title":"The role of collagen in bone apatite formation in the presence of hydroxyapatite nucleation inhibitors","volume":"9","author":"Nudelman","year":"2010","journal-title":"Nat. Mater."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"6316","DOI":"10.1073\/pnas.0914218107","article-title":"Mapping amorphous calcium phosphate transformation into crystalline mineral from the cell to the bone in zebrafish fin rays","volume":"107","author":"Mahamid","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1002\/(SICI)1097-4636(20000615)50:4<518::AID-JBM7>3.0.CO;2-W","article-title":"Formation of calcium phosphate\/collagen composites through mineralization of collagen matrix","volume":"50","author":"Du","year":"2000","journal-title":"J. Biomed. Mater. Res."},{"key":"ref_13","first-page":"215","article-title":"Preparation and characterization of collagen: Amorphous calcium phosphate composites","volume":"12","author":"Vranceanu","year":"2012","journal-title":"Revista de Pielarie Incaltaminte Leather Footwear J."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"22185","DOI":"10.1021\/acsami.7b04776","article-title":"In vitro and in vivo analysis of mineralized collagen-based sponges prepared by a plasma- and precursor-assisted biomimetic process","volume":"9","author":"Nathanael","year":"2017","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"111194","DOI":"10.1016\/j.msec.2020.111194","article-title":"In situ precipitation of amorphous calcium phosphate nanoparticles within 3D porous collagen sponges for bone tissue engineering","volume":"116","author":"Santhakumar","year":"2020","journal-title":"Mater. Sci. Eng. C"},{"key":"ref_16","unstructured":"Kanemoto, Y. (2020). Assessment of Bone Forming Ability of Apatite-Coated Collagen Scaffold Prepared by a Precursor-Assisted Biomimetic Process. [Ph.D. Thesis, Hokkaido University]."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2907","DOI":"10.1016\/j.biomaterials.2006.01.017","article-title":"How useful is SBF in predicting in vivo bone bioactivity?","volume":"27","author":"Kokubo","year":"2006","journal-title":"Biomaterials"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"22602","DOI":"10.1021\/am5067139","article-title":"Osteoconductive property of a mechanical mixture of octacalcium phosphate and amorphous calcium phosphate","volume":"6","author":"Kobayashi","year":"2014","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"45655","DOI":"10.1038\/srep45655","article-title":"Sustained delivery of calcium and orthophosphate ions from amorphous calcium phosphate and poly(L-lactic acid)-based electrospinning nanofibrous scaffold","volume":"7","author":"Niu","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"4690","DOI":"10.1039\/b710936a","article-title":"Effect of crystallinity of calcium phosphate nanoparticles on adhesion, proliferation, and differentiation of bone marrow mesenchymal stem cells","volume":"17","author":"Hu","year":"2007","journal-title":"J. Mater. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1002\/(SICI)1097-4636(200001)49:1<43::AID-JBM6>3.0.CO;2-G","article-title":"Bone growth on and resorption of calcium phosphate coatings obtained by pulsed laser deposition","volume":"49","author":"Morenza","year":"2000","journal-title":"J. Biomed. Mater. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1097\/00003086-200301000-00033","article-title":"Response of a calcium sulfate bone graft substitute in a confined cancellous defect","volume":"406","author":"Walsh","year":"2003","journal-title":"Clin. Orthop. Relat. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1016\/S0142-9612(97)00163-4","article-title":"Short-term implantation effects of a DCPD-based calcium phosphate cement","volume":"19","author":"Frayssinet","year":"1998","journal-title":"Biomaterials"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2175","DOI":"10.1016\/j.biomaterials.2009.01.008","article-title":"Can bioactivity be tested in vitro with SBF solution?","volume":"30","author":"Bohner","year":"2009","journal-title":"Biomaterials"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1097\/00000542-200408000-00029","article-title":"Changes in tissue pH and temperature after incision indicate acidosis may contribute to postoperative pain","volume":"101","author":"Woo","year":"2004","journal-title":"Anesthesiology"},{"key":"ref_26","first-page":"317","article-title":"Bone regeneration: Molecular and cellular interactions with calcium phosphate ceramics","volume":"1","year":"2006","journal-title":"Int. J. Nanomed."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"4457","DOI":"10.1016\/j.actbio.2010.06.031","article-title":"Amorphous calcium (ortho)phosphates","volume":"6","author":"Dorozhkin","year":"2010","journal-title":"Acta Biomater."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1097\/00008505-199807040-00011","article-title":"Dissolution kinetics of calcium phosphate coatings","volume":"7","author":"Burke","year":"1998","journal-title":"Implant Dent."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3362","DOI":"10.1016\/j.actbio.2010.02.017","article-title":"Amorphous calcium phosphates: Synthesis, properties and uses in biomaterials","volume":"6","author":"Combes","year":"2010","journal-title":"Acta Biomater."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1002\/jemt.20274","article-title":"Comparison of bone formation ingrafted periosteum harvested from tibia and calvaria","volume":"69","author":"Fujii","year":"2006","journal-title":"Microsc. Res. Technol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1007\/s13770-013-1094-9","article-title":"Comparison of bone regeneration rate in flat and long bone defects: Calvarial and tibial bone","volume":"10","author":"Lim","year":"2013","journal-title":"Tissue Eng. Regen. Med."}],"container-title":["Materials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1996-1944\/14\/19\/5860\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:10:09Z","timestamp":1760166609000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1996-1944\/14\/19\/5860"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,7]]},"references-count":31,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2021,10]]}},"alternative-id":["ma14195860"],"URL":"https:\/\/doi.org\/10.3390\/ma14195860","relation":{},"ISSN":["1996-1944"],"issn-type":[{"value":"1996-1944","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,7]]}}}