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However, its intrinsic brittleness and low fracture resistance limit its use in load-bearing environments, motivating the use of ionic doping to enhance its properties. Doping with strontium (Sr) is particularly advantageous, as this ion is associated with bone regeneration processes, improves osteogenic response, and favorably modifies the material\u2019s lattice parameters and structural organization. In this work, Sr-doped HAp nanorods (5, 10, and 20%) were synthesized by the hydrothermal method, and their structural, mechanical, and drug delivery properties were investigated, with mechanical testing performed on non-sintered pellets to preserve the characteristics of the as-synthesized material. Drug incorporation and release assays with ciprofloxacin were conducted to evaluate the multifunctional potential for bone healing applications. The results confirmed the successful incorporation of Sr2+ into the hydroxyapatite lattice without the formation of secondary phases. Sr incorporation promoted lattice expansion, resulting in a maximum unit cell volume increase of 10 \u00c53, reduced nanorod length, and increased diffraction peak broadening, while Rietveld refinement revealed Sr occupancies of up to 19.5%. Furthermore, Sr incorporation increased the fracture toughness of the compacted non-sintered materials by up to 385% compared with pure HAp, while preserving the hydroxyapatite structure and enabling efficient ciprofloxacin loading and sustained release. Overall, Sr-doped HAp nanorods demonstrate tunable mechanical and functional properties, highlighting their potential as multifunctional materials for bone-related applications requiring both structural performance and localized therapeutic action.<\/jats:p>","DOI":"10.1021\/acsomega.6c05426","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T13:02:39Z","timestamp":1789995759000},"page":"59351-59366","source":"Crossref","is-referenced-by-count":0,"title":["Strontium-Doped\nHydroxyapatite as a Multifunctional\nPlatform: Tailoring Structural, Mechanical, and Drug Delivery Properties\nfor Bone-Related Applications"],"prefix":"10.1021","volume":"11","author":[{"given":"Kairone de Paula","family":"Amaral","sequence":"first","affiliation":[{"name":"Laborato\u0301rio de Materiais Nanoestruturados para Bioaplicac\u0327o\u0303es , , Av. Presidente Anto\u0302nio Carlos 6.627, Pampulha , , ,","place":["Belo Horizonte, Minas Gerais, Brazil, 31270-901"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-2044-0092","authenticated-orcid":true,"given":"Lui\u0301sa","family":"Arantes Fernandes Vieira","sequence":"additional","affiliation":[{"name":"Laborato\u0301rio de Materiais Nanoestruturados para Bioaplicac\u0327o\u0303es , , Av. Presidente Anto\u0302nio Carlos 6.627, Pampulha , , ,","place":["Belo Horizonte, Minas Gerais, Brazil, 31270-901"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1717-6323","authenticated-orcid":true,"given":"Je\u0301ssica Pauline Nunes","family":"Marinho","sequence":"additional","affiliation":[{"name":"Laborato\u0301rio de Materiais Nanoestruturados para Bioaplicac\u0327o\u0303es , , Av. Presidente Anto\u0302nio Carlos 6.627, Pampulha , , ,","place":["Belo Horizonte, Minas Gerais, Brazil, 31270-901"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-7794-8966","authenticated-orcid":true,"given":"Joa\u0303o Batista Santos","family":"Barbosa","sequence":"additional","affiliation":[{"name":"SEMAV , , Av. Presidente Anto\u0302nio Carlos 6.627, Pampulha , , ,","place":["Belo Horizonte, Minas Gerais, Brazil, 31270-901"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andre\u0301 Felipe de","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Laborato\u0301rio de Materiais Nanoestruturados para Bioaplicac\u0327o\u0303es , , Av. Presidente Anto\u0302nio Carlos 6.627, Pampulha , , ,","place":["Belo Horizonte, Minas Gerais, Brazil, 31270-901"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6317-4054","authenticated-orcid":true,"given":"Ede\u0301sia Martins Barros de","family":"Sousa","sequence":"additional","affiliation":[{"name":"Laborato\u0301rio de Materiais Nanoestruturados para Bioaplicac\u0327o\u0303es , , Av. Presidente Anto\u0302nio Carlos 6.627, Pampulha , , ,","place":["Belo Horizonte, Minas Gerais, Brazil, 31270-901"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,9,21]]},"reference":[{"issue":"3","key":"2026100610465410900_cit1","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1007\/s10856-020-06364-y","article-title":"Scaffolds\nand coatings for bone regeneration","volume":"31","author":"Pereira","year":"2020","journal-title":"J. Mater.\nSci. Mater. Med."},{"issue":"9","key":"2026100610465410900_cit2","doi-asserted-by":"publisher","first-page":"2722","DOI":"10.1016\/j.matt.2022.06.003","article-title":"Scaffolds\nfor bone-tissue engineering","volume":"5","author":"Lee","year":"2022","journal-title":"Matter"},{"key":"2026100610465410900_cit3","doi-asserted-by":"publisher","DOI":"10.1016\/j.bea.2022.100056","article-title":"Mechanical and morphological\ncharacterization\nof nano-hydroxyapatite (nHA) for bone regeneration: A mini review","volume":"4","author":"Abere","year":"2022","journal-title":"Biomed. Eng. Adv."},{"issue":"4","key":"2026100610465410900_cit4","doi-asserted-by":"publisher","first-page":"542","DOI":"10.3390\/ceramics4040039","article-title":"Hydroxyapatite for Biomedical Applications: A Short Overview","volume":"4","author":"Fiume","year":"2021","journal-title":"Ceram. 2021, Vol. 4, Pages 542-563"},{"key":"2026100610465410900_cit5","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1016\/j.bioactmat.2025.02.039","article-title":"From hard tissues to\nbeyond: Progress and challenges of strontium-containing biomaterials\nin regenerative medicine applications","volume":"49","author":"Wang","year":"2025","journal-title":"Bioact.\nMater."},{"issue":"4","key":"2026100610465410900_cit6","doi-asserted-by":"publisher","DOI":"10.1590\/s1517-707620180004.0551","article-title":"Comparative\nstudy between natural and synthetic Hydroxyapatite: structural, morphological\nand bioactivity properties","volume":"23","author":"Sossa","year":"2018","journal-title":"Mate\u0301ria (Rio\nJaneiro)"},{"issue":"3","key":"2026100610465410900_cit7","doi-asserted-by":"publisher","first-page":"568","DOI":"10.1039\/B802841A","article-title":"The structure of\nstrontium-doped hydroxyapatite: An\nexperimental and theoretical study","volume":"11","author":"Terra","year":"2009","journal-title":"Phys. Chem.\nChem. Phys."},{"issue":"1","key":"2026100610465410900_cit8","doi-asserted-by":"publisher","first-page":"012008","DOI":"10.1088\/1742-6596\/2071\/1\/012008","article-title":"Synthesis\nMethods of Doped Hydroxyapatite: A Brief Review","volume":"2071","author":"Baskaran","year":"2021","journal-title":"J. Phys. Conf. Ser."},{"issue":"4","key":"2026100610465410900_cit9","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1387\/ijdb.230091lc","article-title":"Strontium-doped hydroxyapatite\nand its role in osteogenesis and angiogenesis","volume":"67","author":"Ran","year":"2023","journal-title":"Int. J. Dev. 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Int."},{"issue":"6","key":"2026100610465410900_cit13","doi-asserted-by":"publisher","first-page":"1885","DOI":"10.1016\/j.actbio.2008.05.005","article-title":"Strontium-substituted hydroxyapatite coatings synthesized by pulsed-laser\ndeposition: In vitro osteoblast and osteoclast response","volume":"4","author":"Capuccini","year":"2008","journal-title":"Acta Biomater."},{"issue":"1","key":"2026100610465410900_cit14","doi-asserted-by":"publisher","first-page":"717","DOI":"10.1080\/21691401.2021.2016785","article-title":"Nano-hydroxyapatite\nas a delivery\nsystem: overview and advancements","volume":"49","author":"Munir","year":"2021","journal-title":"Artif. Cells,\nNanomedicine Biotechnol."},{"issue":"2","key":"2026100610465410900_cit15","doi-asserted-by":"publisher","first-page":"1291","DOI":"10.3390\/ijms24021291","article-title":"Nano-Hydroxyapatite\nComposite Scaffolds Loaded with Bioactive Factors\nand Drugs for Bone Tissue Engineering","volume":"24","author":"Mo","year":"2023","journal-title":"Int.\nJ. Mol. Sci."},{"issue":"6","key":"2026100610465410900_cit16","doi-asserted-by":"publisher","first-page":"5083","DOI":"10.3390\/ijms24065083","article-title":"The Impact of Hydroxyapatite Sintering\nTemperature on Its Microstructural, Mechanical, and Biological Properties","volume":"24","author":"Trzaskowska","year":"2023","journal-title":"Int. J. Mol. Sci."},{"issue":"3","key":"2026100610465410900_cit17","doi-asserted-by":"publisher","first-page":"274","DOI":"10.1007\/s40145-013-0072-y","article-title":"Sintering effects on chemical and physical properties\nof bioactive ceramics","volume":"2","author":"Witek","year":"2013","journal-title":"J. Adv. Ceram. 2013 23"},{"key":"2026100610465410900_cit18","doi-asserted-by":"publisher","DOI":"10.3389\/fbiom.2022.942104","article-title":"Calcium phosphate\nbioceramics: From cell behavior to chemical-physical properties","volume":"1","author":"Magnaudeix","year":"2022","journal-title":"Front. Biomater. Sci."},{"key":"2026100610465410900_cit19","doi-asserted-by":"publisher","DOI":"10.1016\/j.matchemphys.2020.123910","article-title":"Thermo-physical insights\ninto a series of strontium substituted hydroxyapatite","volume":"258","author":"Erdem Bastan","year":"2021","journal-title":"Mater. Chem. Phys."},{"issue":"12","key":"2026100610465410900_cit20","doi-asserted-by":"publisher","first-page":"1881","DOI":"10.3390\/nano13121881","article-title":"Osteogenic Potential of Nano-Hydroxyapatite\nand Strontium-Substituted Nano-Hydroxyapatite","volume":"13","author":"Kontogianni","year":"2023","journal-title":"Nanomater. 2023, Vol. 13, Page 1881"},{"issue":"2","key":"2026100610465410900_cit21","doi-asserted-by":"publisher","first-page":"1926","DOI":"10.1016\/j.ceramint.2025.12.012","article-title":"Preparation\nand characterization of superhydrophilic Sr-doped hydroxyapatite\ncoatings for medical implant surfaces","volume":"52","author":"Lu","year":"2026","journal-title":"Ceram.\nInt."},{"issue":"6","key":"2026100610465410900_cit22","doi-asserted-by":"publisher","first-page":"1611","DOI":"10.3390\/nano11061611","article-title":"Nanoscale strontium-substituted\nhydroxyapatite pastes and gels for bone tissue regeneration","volume":"11","author":"Harrison","year":"2021","journal-title":"Nanomaterials"},{"key":"2026100610465410900_cit23","doi-asserted-by":"publisher","first-page":"rbaf066","DOI":"10.1093\/rb\/rbaf066","article-title":"Strontium-incorporated hydroxyapatite nanocomposites\npromoting bone formation and angiogenesis by modulating M2 macrophage\npolarization in the bone microenvironment","volume":"12","author":"Li","year":"2025","journal-title":"Regen.\nBiomater."},{"issue":"12","key":"2026100610465410900_cit24","doi-asserted-by":"publisher","first-page":"5264","DOI":"10.1021\/acsabm.3c00539","article-title":"A Comparative\nStudy on Physicochemical Properties and In Vitro Biocompatibility\nof Sr-Substituted and Sr Ranelate-Loaded Hydroxyapatite Nanoparticles","volume":"6","author":"Stipniece","year":"2023","journal-title":"ACS Appl. Bio Mater."},{"issue":"18","key":"2026100610465410900_cit25","doi-asserted-by":"publisher","first-page":"32064","DOI":"10.1016\/J.CERAMINT.2024.06.011","article-title":"Nanocomposite\nbased on hydroxyapatite and boron nitride nanostructures containing\ncollagen and tannic acid ameliorates the mechanical strengthening\nand tumor therapy","volume":"50","author":"Vieira","year":"2024","journal-title":"Ceram. Int."},{"issue":"12","key":"2026100610465410900_cit26","doi-asserted-by":"publisher","first-page":"19932","DOI":"10.1016\/j.ceramint.2023.03.115","article-title":"Nanostructured system based on hydroxyapatite\nand curcumin: A promising candidate for osteosarcoma therapy","volume":"49","author":"Marinho","year":"2023","journal-title":"Ceram. Int."},{"issue":"29","key":"2026100610465410900_cit27","doi-asserted-by":"publisher","first-page":"14501","DOI":"10.1007\/s10853-020-05015-5","article-title":"Microstructure,\nmechanical properties and in vitro\nbiocompatibilities of a novel bionic hydroxyapatite bone scaffold\nprepared by the addition of boron nitride","volume":"55","author":"Wang","year":"2020","journal-title":"J.\nMater. Sci."},{"issue":"2","key":"2026100610465410900_cit28","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2025.e41781","article-title":"A comparative\nX-ray\ndiffraction analysis of Sr2+substituted hydroxyapatite from sand lobster\nshell waste using various methods","volume":"11","author":"Diputra","year":"2025","journal-title":"Heliyon"},{"key":"2026100610465410900_cit29","doi-asserted-by":"publisher","first-page":"653","DOI":"10.1016\/j.msec.2016.10.047","article-title":"Synthesis and characterization of strontium-substituted hydroxyapatite\nnanoparticles for bone regeneration","volume":"71","author":"Frasnelli","year":"2017","journal-title":"Mater.\nSci. Eng. C"},{"key":"2026100610465410900_cit30","doi-asserted-by":"publisher","first-page":"439","DOI":"10.15541\/jim20190439","article-title":"Strontium Doped\nHydroxyapatite Nanoparticles: Synthesis, Characterization and Simulation","author":"ZHOU","year":"2020","journal-title":"J. Inorg. Mater."},{"issue":"1","key":"2026100610465410900_cit31","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1007\/s41779-020-00525-6","article-title":"Synthesis,\ncharacterization, and antimicrobial properties of strontium-substituted\nhydroxyapatite","volume":"57","author":"Kumar","year":"2021","journal-title":"J. Aust. Ceram. Soc."},{"issue":"1","key":"2026100610465410900_cit32","doi-asserted-by":"publisher","first-page":"117","DOI":"10.3390\/cryst13010117","article-title":"Structural\nCharacterization of Low-Sr-Doped Hydroxyapatite Obtained by Solid-State\nSynthesis","volume":"13","author":"Baldassarre","year":"2023","journal-title":"Crystals"},{"issue":"8","key":"2026100610465410900_cit33","doi-asserted-by":"publisher","first-page":"085221","DOI":"10.1063\/1.5034441\/563734","article-title":"Nucleation and growth\nof hydroxyapatite nanocrystals by hydrothermal method","volume":"8","author":"Zhu","year":"2018","journal-title":"AIP Adv."},{"issue":"1","key":"2026100610465410900_cit34","doi-asserted-by":"publisher","first-page":"466","DOI":"10.1021\/cg800738a","article-title":"An effective\nmorphology control of hydroxyapatite crystals via hydrothermal synthesis","volume":"9","author":"Neira","year":"2009","journal-title":"Cryst. Growth Des."},{"issue":"18","key":"2026100610465410900_cit35","doi-asserted-by":"publisher","first-page":"7812","DOI":"10.1039\/D3DT04305C","article-title":"Probing the influence of strontium doping and annealing\ntemperature on the structure and biocompatibility of hydroxyapatite\nnanorods","volume":"53","author":"Patil","year":"2024","journal-title":"Dalt. Trans."},{"issue":"1","key":"2026100610465410900_cit36","doi-asserted-by":"publisher","first-page":"5915","DOI":"10.1038\/s41598-019-42269-9","article-title":"Effect of the Nano Crystal Size on\nthe X-ray Diffraction Patterns of Biogenic Hydroxyapatite from Human,\nBovine, and Porcine Bones","volume":"9","author":"London\u0303o-Restrepo","year":"2019","journal-title":"Sci. Reports 2019\n91"},{"issue":"1","key":"2026100610465410900_cit37","doi-asserted-by":"publisher","first-page":"4513","DOI":"10.1038\/s41598-023-30996-z","article-title":"Biomimetic ion substituted\nand Co-substituted hydroxyapatite\nnanoparticle synthesis using Serratia Marcescens","volume":"13","author":"Paramasivan","year":"2023","journal-title":"Sci. Reports 2023 131"},{"issue":"12","key":"2026100610465410900_cit38","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s11051-020-05105-0","article-title":"Multifunctional\nhybrid nanosystems based on mesoporous silica and hydroxyapatite nanoparticles\napplied as potential nanocarriers for theranostic applications","volume":"22","author":"dos Apostolos","year":"2020","journal-title":"J. Nanoparticle Res."},{"issue":"6","key":"2026100610465410900_cit39","doi-asserted-by":"publisher","first-page":"1162","DOI":"10.1134\/S1027451011120068","article-title":"X-ray diffraction and IR spectroscopy\ninvestigation of synthesized and biogenic nanocrystalline hydroxyapatite","volume":"5","author":"Kashkarov","year":"2011","journal-title":"J. Surf. Investig."},{"issue":"21","key":"2026100610465410900_cit40","doi-asserted-by":"publisher","first-page":"14625","DOI":"10.1039\/D3RA02580B","article-title":"FTIR spectrum analysis to predict\nthe crystalline and amorphous phases of hydroxyapatite: a comparison\nof vibrational motion to reflection","volume":"13","author":"Sahadat Hossain","year":"2023","journal-title":"RSC Adv."},{"issue":"4","key":"2026100610465410900_cit41","doi-asserted-by":"publisher","first-page":"1315","DOI":"10.1007\/s41779-024-01041-7","article-title":"Effect of strontium substitution\non the properties\nof mesoporous carbonate apatite for biomedical applications","volume":"60","author":"Bang","year":"2024","journal-title":"J. Aust. Ceram. Soc."},{"key":"2026100610465410900_cit42","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1016\/j.actbio.2015.06.001","article-title":"Chemical and\nphysical properties of carbonated hydroxyapatite affect breast cancer\ncell behavior","volume":"24","author":"Choi","year":"2015","journal-title":"Acta Biomater."},{"key":"2026100610465410900_cit43","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1016\/j.matchemphys.2016.06.063","article-title":"Synthesis and characterization of 159Gd-doped hydroxyapatite\nnanorods for bioapplications as theranostic systems","volume":"181","author":"Cipreste","year":"2016","journal-title":"Mater. Chem. Phys."},{"issue":"23","key":"2026100610465410900_cit44","doi-asserted-by":"publisher","first-page":"32775","DOI":"10.1016\/j.ceramint.2021.08.174","article-title":"Synthesis\nand characterization of bioinspired nano-hydroxyapatite by wet chemical\nprecipitation","volume":"47","author":"Gomez-Vazquez","year":"2021","journal-title":"Ceram. Int."},{"issue":"2","key":"2026100610465410900_cit45","first-page":"630","article-title":"Bioactivity, Cytotoxicity\nand Antibacterial Evaluation of Undoped,\nZn-doped, Sr-doped, and Zn\/Sr-codoped Hydroxyapatites Synthesized\nby a Sol-gel Method","volume":"44","author":"Mai","year":"2017","journal-title":"Chiang Mai J. Sci."},{"key":"2026100610465410900_cit46","doi-asserted-by":"publisher","DOI":"10.1002\/9780470106310.ch13","volume-title":"Fourier Transform\nInfrared Spectrometry","author":"Griffiths","year":"2007","edition":"2"},{"issue":"8","key":"2026100610465410900_cit47","doi-asserted-by":"publisher","first-page":"11073","DOI":"10.1016\/j.ceramint.2019.02.194","article-title":"Effects of strontium substitution on the structural distortion of\nhydroxyapatite by rietveld refinement and Raman Spectroscopy","volume":"45","author":"Cheng","year":"2019","journal-title":"Ceram. Int."},{"issue":"5","key":"2026100610465410900_cit48","doi-asserted-by":"publisher","first-page":"1455","DOI":"10.1016\/j.actbio.2008.04.018","article-title":"Structural analysis\nof a series of strontium-substituted apatites","volume":"4","author":"O\u2019Donnell","year":"2008","journal-title":"Acta Biomater."},{"issue":"3","key":"2026100610465410900_cit49","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1002\/(SICI)1097-0282(2000)57:3&lt;129::AID-BIP1&gt;3.0.CO;2-O","article-title":"Two-dimensional\nvibrational correlation spectroscopy of in vitro hydroxyapatite maturation","volume":"57","author":"Ou-Yang","year":"2000","journal-title":"Biopolym. - Biospectroscopy Sect."},{"issue":"6","key":"2026100610465410900_cit50","doi-asserted-by":"publisher","first-page":"384","DOI":"10.1007\/BF02554969","article-title":"Resolution-enhanced\nfourier transform infrared spectroscopy study of the environment of\nphosphate ions in the early deposits of a solid phase of calcium-phosphate\nin bone and enamel, and their evolution with age. 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