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Transforming eggshell calcite particles into calcium phosphate (apatite) micro-nanoparticles opens the door to repurposing the eggshell waste as materials with potential biomedical applications, fulfilling the principles of the circular economy. Previous methods to obtain these particles consisted mainly of two steps, the first one involving the calcination of the eggshell. In this research, direct transformation by a one-pot hydrothermal method ranging from 100\u2013200 \u00b0C was studied, using suspensions with a stoichiometric P\/CaCO3 ratio, K2HPO4 as P reagent, and eggshells particles (\u00d8 &lt; 50 \u03bcm) both untreated and treated with NaClO to remove surface organic matter. In the untreated group, the complete conversion was achieved at 160 \u00b0C, and most particles displayed a hexagonal plate morphology, eventually with a central hole. In the treated group, this replacement occurred at 180 \u00b0C, yielding granular (spherulitic) apatite nanoparticles. The eggshell particles and apatite micro-nanoparticles were cytocompatible when incubated with MG-63 human osteosarcoma cells and m17.ASC murine mesenchymal stem cells and promoted the osteogenic differentiation of m17.ASC cells. The study results are useful for designing and fabricating biocompatible microstructured materials with osteoinductive properties for applications in bone tissue engineering and dentistry.<\/jats:p>","DOI":"10.3390\/nano13162299","type":"journal-article","created":{"date-parts":[[2023,8,10]],"date-time":"2023-08-10T10:24:47Z","timestamp":1691663087000},"page":"2299","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Hydrothermal Transformation of Eggshell Calcium Carbonate into Apatite Micro-Nanoparticles: Cytocompatibility and Osteoinductive Properties"],"prefix":"10.3390","volume":"13","author":[{"given":"Adriana","family":"Torres-Mansilla","sequence":"first","affiliation":[{"name":"Departament of Geology, University of Oviedo, 33005 Oviedo, Spain"},{"name":"Laboratory of Crystallographic Studies, IACT-CSIC-University of Granada, Avda. Las Palmeras, n\u00b0 4, 18100 Armilla, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5325-183X","authenticated-orcid":false,"given":"Pedro","family":"\u00c1lvarez-Lloret","sequence":"additional","affiliation":[{"name":"Departament of Geology, University of Oviedo, 33005 Oviedo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raquel","family":"Fern\u00e1ndez-Penas","sequence":"additional","affiliation":[{"name":"Laboratory of Crystallographic Studies, IACT-CSIC-University of Granada, Avda. Las Palmeras, n\u00b0 4, 18100 Armilla, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annarita","family":"D\u2019Urso","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze della Salute, Universit\u00e0 del Piemonte Orientale, \u201cA. Avogadro\u201d Via Solaroli, 17, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3134-9198","authenticated-orcid":false,"given":"Paula Alejandra","family":"Baldi\u00f3n","sequence":"additional","affiliation":[{"name":"Departament of Oral Health, Faculty of Dentistry, Universidad Nacional de Colombia, Bogot\u00e1 111321, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0613-6166","authenticated-orcid":false,"given":"Francesca","family":"Oltolina","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze della Salute, Universit\u00e0 del Piemonte Orientale, \u201cA. Avogadro\u201d Via Solaroli, 17, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonia","family":"Follenzi","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze della Salute, Universit\u00e0 del Piemonte Orientale, \u201cA. Avogadro\u201d Via Solaroli, 17, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9395-7797","authenticated-orcid":false,"given":"Jaime","family":"G\u00f3mez-Morales","sequence":"additional","affiliation":[{"name":"Laboratory of Crystallographic Studies, IACT-CSIC-University of Granada, Avda. Las Palmeras, n\u00b0 4, 18100 Armilla, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1016\/j.crpv.2004.08.002","article-title":"Avian Eggshell Mineralization; Biochemical and Functional Characterization of Matrix Proteins","volume":"3","author":"Nys","year":"2004","journal-title":"Comptes Rendus Palevol"},{"key":"ref_2","unstructured":"Hincke, M., Gautron, J., Rodriguez-Navarro, A.B., and McKee, M.D. (2011). Improving the Safety and Quality of Eggs and Egg Products: Egg Chemistry, Production and Consumption, Elsevier."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"3801","DOI":"10.1002\/pmic.200600120","article-title":"Proteomic Analysis of the Acid-Soluble Organic Matrix of the Chicken Calcified Eggshell Layer","volume":"6","author":"Mann","year":"2006","journal-title":"Proteomics"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1754","DOI":"10.1016\/j.jcrysgro.2007.11.170","article-title":"Influence of Eggshell Matrix Proteins on the Precipitation of Calcium Carbonate (CaCO3)","volume":"310","author":"Vidal","year":"2008","journal-title":"J. Cryst. Growth"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"4330","DOI":"10.1021\/cg800786s","article-title":"Identification of Some Active Proteins in the Process of Hen Eggshell Formation","volume":"8","author":"Gautron","year":"2008","journal-title":"Cryst. Growth Des."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2174\/2212798411103010001","article-title":"Recent Patents on Eggshell: Shell and Membrane Applications","volume":"3","author":"Cordeiro","year":"2011","journal-title":"Recent Pat. Food Nutr. Agric."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Torres-Mansilla, A., Hincke, M., Voltes, A., L\u00f3pez-Ruiz, E., Baldi\u00f3n, P.A., Marchal, J.A., \u00c1lvarez-Lloret, P., and G\u00f3mez-Morales, J. (2023). Eggshell Membrane as a Biomaterial for Bone Regeneration. Polymers, 15.","DOI":"10.3390\/polym15061342"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/j.tifs.2019.07.021","article-title":"Eggshell Calcium: A Cheap Alternative to Expensive Supplements","volume":"91","author":"Waheed","year":"2019","journal-title":"Trends Food Sci. Technol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1623","DOI":"10.1016\/j.biortech.2007.04.010","article-title":"Utilization of Ground Eggshell Waste as an Adsorbent for the Removal of Dyes from Aqueous Solution","volume":"99","author":"Tsai","year":"2008","journal-title":"Bioresour. Technol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1016\/j.chemosphere.2015.12.002","article-title":"Influence of Milling on the Adsorption Ability of Eggshell Waste","volume":"146","year":"2016","journal-title":"Chemosphere"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1016\/j.apenergy.2013.10.004","article-title":"Effective Conversion of Non-Edible Oil with High Free Fatty Acid into Biodiesel by Sulphonated Carbon Catalyst","volume":"114","author":"Dawodu","year":"2014","journal-title":"Appl. Energy"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"012001","DOI":"10.1088\/1755-1315\/755\/1\/012001","article-title":"The Effect of Eggshell Organic Fertilizer on Vegetative Growth of Cayenne Pepper (Capsicum frutescens L)","volume":"755","author":"Anugrah","year":"2021","journal-title":"IOP Conf. Ser. Earth Environ. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Dekhtyar, Y., Katashev, A., and Lancere, L. (2013). Proceedings of the International Symposium on Biomedical Engineering and Medical Physics, Riga, Latvia, 10\u201312 October 2012, Springer.","DOI":"10.1007\/978-3-642-34197-7"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.pcrysgrow.2012.11.001","article-title":"Progress on the Preparation of Nanocrystalline Apatites and Surface Characterization: Overview of Fundamental and Applied Aspects","volume":"59","author":"Iafisco","year":"2013","journal-title":"Prog. Cryst. Growth Charact. Mater."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1016\/j.actbio.2009.10.031","article-title":"Nanosized and Nanocrystalline Calcium Orthophosphates","volume":"6","author":"Dorozhkin","year":"2010","journal-title":"Acta Biomater."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"S11","DOI":"10.4103\/jpbs.JPBS_683_20","article-title":"Nano-Hydroxyapatite: A Driving Force for Bone Tissue Engineering","volume":"13","author":"Rajula","year":"2021","journal-title":"J. Pharm. Bioallied Sci."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Lara-Ochoa, S., Ortega-Lara, W., and Guerrero-Beltr\u00e1n, C.E. (2021). Hydroxyapatite Nanoparticles in Drug Delivery: Physicochemistry and Applications. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13101642"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"G\u00f3mez-Morales, J., Fern\u00e1ndez-Penas, R., Acebedo-Mart\u00ednez, F.J., Romero-Castillo, I., Verdugo-Escamilla, C., Choquesillo-Lazarte, D., Esposti, L.D., Jim\u00e9nez-Mart\u00ednez, Y., Fern\u00e1ndez-S\u00e1nchez, J.F., and Iafisco, M. (2022). Luminescent Citrate-Functionalized Terbium-Substituted Carbonated Apatite Nanomaterials: Structural Aspects, Sensitized Luminescence, Cytocompatibility, and Cell Uptake Imaging. Nanomaterials, 12.","DOI":"10.3390\/nano12081257"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Cano Pl\u00e1, S.M., D\u2019Urso, A., Fern\u00e1ndez-S\u00e1nchez, J.F., Colangelo, D., Choquesillo-Lazarte, D., Ferracini, R., Bosetti, M., Prat, M., and G\u00f3mez-Morales, J. (2022). Biomimetic Citrate-Coated Luminescent Apatite Nanoplatforms for Diclofenac Delivery in Inflammatory Environments. Nanomaterials, 12.","DOI":"10.3390\/nano12030562"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2385","DOI":"10.1039\/C7RA12536D","article-title":"Luminescent Biomimetic Citrate-Coated Europium-Doped Carbonated Apatite Nanoparticles for Use in Bioimaging: Physico-Chemistry and Cytocompatibility","volume":"8","author":"Drouet","year":"2018","journal-title":"RSC Adv."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1016\/j.smaim.2023.06.004","article-title":"Platinum nanoparticles enhance osteogenic differentiation of human dental follicle stem cells via scavenging ROS","volume":"4","author":"Wang","year":"2023","journal-title":"Smart Mater. Med."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Nigar, F., Johnston, A.-L., Smith, J., Oakley, W., Islam, M.T., Felfel, R., Grant, D., Lester, E., and Ahmed, I. (2023). Production of Nano Hydroxyapatite and Mg-Whitlockite from Biowaste-Derived Products via Continuous Flow Hydrothermal Synthesis: A Step towards Circular Economy. Materials, 16.","DOI":"10.3390\/ma16062138"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"105748","DOI":"10.1016\/j.jmbbm.2023.105748","article-title":"Micro-Raman Spectroscopy Analysis of Dentin Remineralization Using Eggshell Derived Nanohydroxyapatite Combined with Phytosphingosine","volume":"141","author":"Rajkumar","year":"2023","journal-title":"J. Mech. Behav. Biomed. Mater."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"18708","DOI":"10.1016\/j.ceramint.2023.02.248","article-title":"Preparation and Analysis of Pure and Surface Modified Nanohydroxyapatite Derived from Eggshells and Its In-Vitro Studies for Bone Graft Applications","volume":"49","author":"Sindhya","year":"2023","journal-title":"Ceram. Int."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"012024","DOI":"10.1088\/1757-899X\/1189\/1\/012024","article-title":"Synthesis of Eggshell Based Hydroxyapatite Using Hydrothermal Method","volume":"1189","author":"Hussain","year":"2021","journal-title":"IOP Conf. Ser. Mater. Sci. Eng."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e03655","DOI":"10.1016\/j.heliyon.2020.e03655","article-title":"A Novel Hydrothermal Synthesis of Nanohydroxyapatite from Eggshell-Calcium-Oxide Precursors","volume":"6","author":"Noviyanti","year":"2020","journal-title":"Heliyon"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Fern\u00e1ndez-Penas, R., Verdugo-Escamilla, C., Triunfo, C., G\u00e4rtner, S., D\u2019Urso, A., Oltolina, F., Follenzi, A., Maoloni, G., C\u00f6lfen, H., and Falini, G. (2023). Sustainable One-Pot Path to Transform Seashell Waste Calcium Carbonate to Osteoinductive Hydroxyapatite Micro-Nanoparticles. J. Mater. Chem. B.","DOI":"10.1039\/D3TB00856H"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"bio059536","DOI":"10.1242\/bio.059536","article-title":"An Alternative and Effective Method for Extracting Skeletal Organic Matrix Adapted to the Red Coral Corallium Rubrum","volume":"11","author":"Ganot","year":"2022","journal-title":"Biol. Open"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2873","DOI":"10.1089\/scd.2012.0718","article-title":"Isolation and Characterization of a Spontaneously Immortalized Multipotent Mesenchymal Cell Line Derived from Mouse Subcutaneous Adipose Tissue","volume":"22","author":"Zamperone","year":"2013","journal-title":"Stem Cells Dev."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1038\/nature10137","article-title":"Role of YAP\/TAZ in Mechanotransduction","volume":"474","author":"Dupont","year":"2011","journal-title":"Nature"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Sutthavas, P., Schumacher, M., Zheng, K., Habibovi\u0107, P., Boccaccini, A.R., and van Rijt, S. (2022). Zn-Loaded and Calcium Phosphate-Coated Degradable Silica Nanoparticles Can Effectively Promote Osteogenesis in Human Mesenchymal Stem Cells. Nanomaterials, 12.","DOI":"10.3390\/nano12172918"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"eaar3219","DOI":"10.1126\/sciadv.aar3219","article-title":"Nanostructure, Osteopontin, and Mechanical Properties of Calcitic Avian Eggshell","volume":"4","author":"Athanasiadou","year":"2018","journal-title":"Sci. Adv."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1016\/j.colsurfb.2018.09.039","article-title":"Facile Synthesis of Hydroxyapatite Nanoparticles Mimicking Biological Apatite from Eggshells for Bone-Tissue Engineering","volume":"172","author":"Nga","year":"2018","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"892","DOI":"10.1002\/jrs.1518","article-title":"Raman and Infrared Spectra of Carbonates of Calcite Structure","volume":"37","author":"Gunasekaran","year":"2006","journal-title":"J. Raman Spectrosc."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"33985","DOI":"10.1039\/C8RA06608F","article-title":"Vibrational Properties of Isotopically Enriched Materials: The Case of Calcite","volume":"8","author":"Xu","year":"2018","journal-title":"RSC Adv."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"17634","DOI":"10.1039\/C4CP01772B","article-title":"Linking Crystal Structure with Temperature-Sensitive Vibrational Modes in Calcium Carbonate Minerals","volume":"16","author":"Xu","year":"2014","journal-title":"Phys. Chem. Chem. Phys."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"119980","DOI":"10.1016\/j.saa.2021.119980","article-title":"Identification and Composition of Carbonate Minerals of the Calcite Structure by Raman and Infrared Spectroscopies Using Portable Devices","volume":"261","author":"Kim","year":"2021","journal-title":"Spectrochim. Acta Part A Mol. Biomol. Spectrosc."},{"key":"ref_38","unstructured":"Rey, C., Marsan, O., Combes, C., Drouet, C., Grossin, D., and Sarda, S. (2014). Advances in Calcium Phosphate Biomaterials, Springer."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.jas.2014.05.004","article-title":"Revisiting Carbonate Quantification in Apatite (Bio)Minerals: A Validated FTIR Methodology","volume":"49","author":"Grunenwald","year":"2014","journal-title":"J. Archaeol. Sci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/cc644","article-title":"Determinants of Blood PH in Health and Disease","volume":"4","author":"Kellum","year":"2000","journal-title":"Crit. Care"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"415S","DOI":"10.1093\/jn\/138.2.415S","article-title":"Extracellular PH Regulates Bone Cell Function","volume":"138","author":"Arnett","year":"2008","journal-title":"J. Nutr."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1146\/annurev-physiol-021119-034627","article-title":"The Acidic Tumor Microenvironment as a Driver of Cancer","volume":"82","author":"Boedtkjer","year":"2020","journal-title":"Annu. Rev. Physiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/j.bbamcr.2014.11.022","article-title":"Acidic Environment Activates Inflammatory Programs in Fibroblasts via a CAMP-MAPK Pathway","volume":"1853","author":"Riemann","year":"2015","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"905","DOI":"10.2147\/DDDT.S299641","article-title":"Hydroxyapatite Nanoparticles Facilitate Osteoblast Differentiation and Bone Formation Within Sagittal Suture During Expansion in Rats","volume":"15","author":"Liang","year":"2021","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1186\/s11671-021-03522-1","article-title":"Potential Osteoinductive Effects of Hydroxyapatite Nanoparticles on Mesenchymal Stem Cells by Endothelial Cell Interaction","volume":"16","author":"Wang","year":"2021","journal-title":"Nanoscale Res. Lett."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"6439","DOI":"10.1021\/nn101373r","article-title":"Gold Nanoparticles Promote Osteogenic Differentiation of Mesenchymal Stem Cells through P38 MAPK Pathway","volume":"4","author":"Yi","year":"2010","journal-title":"ACS Nano"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.chemgeo.2014.06.007","article-title":"Coupled Dissolution and Precipitation at Mineral\u2013Fluid Interfaces","volume":"383","author":"Putnis","year":"2014","journal-title":"Chem. Geol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.susc.2014.01.008","article-title":"Reassigning the Most Stable Surface of Hydroxyapatite to the Water Resistant Hydroxyl Terminated (010) Surface","volume":"623","author":"Zeglinski","year":"2014","journal-title":"Surf. Sci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1016\/j.msec.2004.01.005","article-title":"Hydrothermal Conversion of Calcite Crystals to Hydroxyapatite","volume":"24","author":"Yoshimura","year":"2004","journal-title":"Mater. Sci. Eng. C"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"8183","DOI":"10.1016\/j.ceramint.2013.03.094","article-title":"A Hydrothermal Synthesis of Eggshell and Fruit Waste Extract to Produce Nanosized Hydroxyapatite","volume":"39","author":"Wu","year":"2013","journal-title":"Ceram. Int."},{"key":"ref_51","unstructured":"(2009). Biological Evaluation of Medical Devices \u2014 Part 5: Tests for In Vitro Cytotoxicity (Standard No. ISO 10993-5:2009). Available online: https:\/\/www.iso.org\/standard\/36406.html."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1016\/j.smaim.2023.04.001","article-title":"Eggshell-derived amorphous calcium phosphate: Synthesis, characterization and bio-functions as bone graft materials in novel 3D osteoblastic spheroids model","volume":"4","author":"Ma","year":"2023","journal-title":"Smart Mater. Med."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Levingstone, T.J., Herbaj, S., and Dunne, N.J. (2019). Calcium Phosphate Nanoparticles for Therapeutic Applications in Bone Regeneration. Nanomaterials, 9.","DOI":"10.3390\/nano9111570"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.pnsc.2018.09.004","article-title":"Calcium carbonate nanoparticles promote osteogenesis compared to adipogenesis in human bone-marrow mesenchymal stem cells","volume":"28","author":"Li","year":"2018","journal-title":"Prog. Nat. Sci. Mater. Int."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"3205","DOI":"10.1016\/j.biomaterials.2012.01.020","article-title":"A calcium-induced signaling cascade leading to osteogenic differentiation of human bone marrow-derived mesenchymal stromal cells","volume":"33","author":"Barradas","year":"2012","journal-title":"Biomaterials"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"29119.e25","DOI":"10.1074\/jbc.M801774200","article-title":"BMP2 regulates osterix through Msx2 and Runx2 during osteoblast differentiation","volume":"283","author":"Matsubara","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"e2036176","DOI":"10.1155\/2018\/2036176","article-title":"In Vitro Uptake of Hydroxyapatite Nanoparticles and Their Effect on Osteogenic Differentiation of Human Mesenchymal Stem Cells","volume":"2018","author":"Yang","year":"2018","journal-title":"Stem Cells Int."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.bbrc.2010.01.109","article-title":"Extracellular calcium modulates in vitro bone marrow-derived Flk-1 \u00fe CD34\u00fe progenitor cell chemotaxis and differentiation through a calcium-sensing receptor","volume":"393","author":"Aguirre","year":"2010","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"393.e9","DOI":"10.1016\/j.bbrc.2010.11.129","article-title":"Involvement of calcium-sensing receptor in inhibition of lipolysis through intracellular cAMP and calcium pathways in human adipocytes","volume":"404","author":"He","year":"2011","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1131.e44","DOI":"10.1124\/mol.109.058784","article-title":"Agonists and allosteric modulators of the Calcium-Sensing Receptor and Their Therapeutic Applications","volume":"76","author":"Saidak","year":"2009","journal-title":"Mol. Pharmacol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.mattod.2015.10.008","article-title":"Calcium Phosphates in Biomedical Applications: Materials for the Future?","volume":"19","author":"Habraken","year":"2016","journal-title":"Mater. Today"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1007\/s11706-013-0204-x","article-title":"Conversion of Natural Marine Skeletons as Scaffolds for Bone Tissue Engineering","volume":"7","author":"Zhang","year":"2013","journal-title":"Front. Mater. Sci."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1007\/s10856-015-5630-0","article-title":"Osteogenic Cell Response to 3-D Hydroxyapatite Scaffolds Developed via Replication of Natural Marine Sponges","volume":"27","author":"Clarke","year":"2016","journal-title":"J. Mater. Sci. Mater. Med."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.tibtech.2016.10.003","article-title":"Natural and Synthetic Coral Biomineralization for Human Bone Revitalization","volume":"35","author":"Green","year":"2017","journal-title":"Trends Biotechnol."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Chen, L., Al-Bayatee, S., Khurshid, Z., Shavandi, A., Brunton, P., and Ratnayake, J. (2021). Hydroxyapatite in Oral Care Products\u2014A Review. Materials, 14.","DOI":"10.3390\/ma14174865"}],"container-title":["Nanomaterials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-4991\/13\/16\/2299\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:30:19Z","timestamp":1760128219000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-4991\/13\/16\/2299"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,10]]},"references-count":65,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2023,8]]}},"alternative-id":["nano13162299"],"URL":"https:\/\/doi.org\/10.3390\/nano13162299","relation":{},"ISSN":["2079-4991"],"issn-type":[{"value":"2079-4991","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,10]]}}}