{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T20:50:17Z","timestamp":1786740617673,"version":"build-2736575974"},"reference-count":45,"publisher":"American Chemical Society (ACS)","issue":"2","license":[{"start":{"date-parts":[[2019,10,22]],"date-time":"2019-10-22T00:00:00Z","timestamp":1571702400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2019,10,22]],"date-time":"2019-10-22T00:00:00Z","timestamp":1571702400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2019,10,22]],"date-time":"2019-10-22T00:00:00Z","timestamp":1571702400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/501100001411","name":"Indian Council of Medical Research","doi-asserted-by":"publisher","award":["MHRD_IITK_006"],"award-info":[{"award-number":["MHRD_IITK_006"]}],"id":[{"id":"10.13039\/501100001411","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001403","name":"Indian Institute of Technology Kanpur","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001403","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001407","name":"Department of Biotechnology , Ministry of Science and Technology","doi-asserted-by":"publisher","award":["BT\/IN\/Sweden\/08\/AK\/2017-18"],"award-info":[{"award-number":["BT\/IN\/Sweden\/08\/AK\/2017-18"]}],"id":[{"id":"10.13039\/501100001407","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001409","name":"Department of Science and Technology, Ministry of Science and Technology","doi-asserted-by":"publisher","award":["DST\/INT\/SWD\/P-11\/2016"],"award-info":[{"award-number":["DST\/INT\/SWD\/P-11\/2016"]}],"id":[{"id":"10.13039\/501100001409","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001409","name":"Department of Science and Technology, Ministry of Science and Technology","doi-asserted-by":"publisher","award":["DST\/NM\/NT-2018\/48"],"award-info":[{"award-number":["DST\/NM\/NT-2018\/48"]}],"id":[{"id":"10.13039\/501100001409","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004541","name":"Ministry of Human Resource Development","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004541","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,2,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Hip fractures are among the most common types of fracture risks in old age osteoporotic patients that often end up with immobile disabilities. Weak bones due to loss of mineral content along with an increase in the porosity of the femur neck canal in osteoporosis reduce the mechanical properties of the bone and predispose the patients to fractures. In this study, we have used calcium sulfate\/nanohydroxyapatite based nanocement (NC) as carrier of recombinant human bone morphogenetic protein-2 (BMP-2), zoledronate (ZA), and bone marrow mesenchymal stromal cells (MSCs) derived exosomes (EXO) to enhance bone formation and defect healing in a femur neck canal defect model in osteoporotic rats. A cylindrical defect in the femur neck canal with dimensions of 1 mm (diameter) \u00d7 8 mm (length) starting from the lateral cortex toward the apex of the femur head was developed. The defect was impacted using NC alone or functionalized as (a) NC + ZA (systemic), (b) NC + ZA (local), (c) NC + EXO + ZA, and (d) NC + BMP + ZA to evaluate bone formation by ex vivo micro-computed tomography (micro-CT) and histological analysis 16 weeks postsurgery. Moreover, the femurs (both defect and contralateral leg) were subjected to biomechanical analysis to assess the effect of treatments on compressive mechanical properties of the bones. The treatment groups (NC + ZA (L), NC + BMP + ZA, and NC + EXO + ZA) showed enhanced bone formation with complete healing of the defect. No differences in the mechanical properties of both the defect and contralateral across the leg were observed among the groups. However, a trend was observed where NC + BMP + ZA showed enhanced biomechanical strength in the defect leg. This suggests that NC could act as a potent carrier of bioactive molecules to reduce the risks of hip fractures in osteoporotic animals. This type of treatment can be given to patients who are at higher risk of osteoporosis mediated femur neck fracture as a preventive measure or for enhanced healing in already compromised situations. Moreover, this study provided a proof of concept regarding the use of exosomes in bone regeneration therapy, which might be used as a booster dose that will eventually reduce the dosage of BMP and hence circumvent the limitations associated with the use of BMP.<\/jats:p>","DOI":"10.1021\/acs.biomac.9b01327","type":"journal-article","created":{"date-parts":[[2019,10,22]],"date-time":"2019-10-22T08:22:41Z","timestamp":1571732561000},"page":"328-337","source":"Crossref","is-referenced-by-count":54,"title":["Nanohydroxyapatite Based Ceramic Carrier Promotes\nBone Formation in a Femoral Neck Canal Defect in Osteoporotic Rats"],"prefix":"10.1021","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7745-4527","authenticated-orcid":true,"given":"Irfan","family":"Qayoom","sequence":"first","affiliation":[{"name":"Indian Institute of Technology Kanpur , , , ,","place":["Kanpur, Uttar Pradesh, India, 208016"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0031-6155","authenticated-orcid":true,"given":"Arun Kumar","family":"Teotia","sequence":"additional","affiliation":[{"name":"Indian Institute of Technology Kanpur , , , ,","place":["Kanpur, Uttar Pradesh, India, 208016"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4910-9440","authenticated-orcid":true,"given":"Ashok","family":"Kumar","sequence":"additional","affiliation":[{"name":"Indian Institute of Technology Kanpur , , , ,","place":["Kanpur, Uttar Pradesh, India, 208016"]},{"name":"Indian Institute of Technology Kanpur , , , ,","place":["Kanpur, Uttar Pradesh, India, 208016"]},{"name":"Indian Institute of Technology Kanpur , , , ,","place":["Kanpur, Uttar Pradesh, India, 208016"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2019,10,22]]},"reference":[{"key":"2026081416130072100_cit1","doi-asserted-by":"publisher","first-page":"117","DOI":"10.2147\/CIA.S85551","article-title":"Fracture liaison services:\nimproving outcomes for patients with osteoporosis","volume":"12","author":"Walters","year":"2017","journal-title":"Clin. Interventions Aging"},{"issue":"1","key":"2026081416130072100_cit2","doi-asserted-by":"publisher","first-page":"46","DOI":"10.5152\/eurjrheum.2016.048","article-title":"An Overview and Management of Osteoporosis","volume":"4","author":"So\u0308zen","year":"2017","journal-title":"Eur. J. Rheumatol."},{"issue":"11","key":"2026081416130072100_cit3","doi-asserted-by":"publisher","first-page":"818","DOI":"10.7326\/M15-1361","article-title":"Treatment of Low\nBone Density or Osteoporosis to Prevent Fractures in Men and Women:\nA Clinical Practice Guideline Update From the American College of\nPhysicians","volume":"166","author":"Qaseem","year":"2017","journal-title":"Ann. Intern. Med."},{"key":"2026081416130072100_cit4","unstructured":"What is Osteoporosis and What Causes It?; https:\/\/www.nof.org\/patients\/what-is-osteoporosis."},{"key":"2026081416130072100_cit5","volume-title":"Bone Health and Osteoporosis","author":"Office of the Surgeon General\n(US)","year":"2004"},{"issue":"1\u20132","key":"2026081416130072100_cit6","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1007\/s11657-013-0136-1","article-title":"Osteoporosis in the European Union:\nMedical Management","volume":"8","author":"Hernlund","year":"2013","journal-title":"Epidemiology and Economic\nBurden. Arch. Osteoporos."},{"key":"2026081416130072100_cit7","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1016\/j.ijotn.2017.04.004","article-title":"Reprint of:\nThe Impact\nof Fragility Fracture and Approaches to Osteoporosis Risk Assessment\nWorldwide","volume":"26","author":"Curtis","year":"2017","journal-title":"Int. J. Orthop. 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Med."},{"issue":"6","key":"2026081416130072100_cit9","doi-asserted-by":"publisher","first-page":"508","DOI":"10.1016\/S1470-2045(06)70726-4","article-title":"Bisphosphonate-associated\nosteonecrosis:\na long-term complication of bisphosphonate treatment","volume":"7","author":"Migliorati","year":"2006","journal-title":"Lancet Oncol."},{"issue":"10","key":"2026081416130072100_cit10","doi-asserted-by":"publisher","first-page":"548","DOI":"10.1302\/2046-3758.710.BJR-2018-0015.R2","article-title":"Anabolic and Antiresorptive\nActions of Locally Delivered Bisphosphonates for Bone Repair","volume":"7","author":"Qayoom","year":"2018","journal-title":"Bone Joint Res."},{"issue":"1","key":"2026081416130072100_cit11","doi-asserted-by":"publisher","first-page":"OC04","DOI":"10.7860\/JCDR\/2016\/17061.7021","article-title":"Study of Adverse\nEffect Profile of\nParenteral Zoledronic Acid in Female Patients with Osteoporosis","volume":"10","author":"Kotian","year":"2016","journal-title":"J. Clin. 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Mater.\nInterfaces"},{"key":"2026081416130072100_cit26","doi-asserted-by":"publisher","first-page":"580","DOI":"10.4236\/msa.2012.38083","article-title":"In Situ Hydroxyapatite Synthesis:\nInfluence of Collagen on Its Structural and Morphological Characteristic","volume":"3","author":"Mendes","year":"2012","journal-title":"Mater. Sci. Appl."},{"issue":"1","key":"2026081416130072100_cit27","doi-asserted-by":"publisher","first-page":"26033","DOI":"10.1038\/srep26033","article-title":"A Biphasic Calcium Sulphate\/Hydroxyapatite Carrier\nContaining Bone Morphogenic Protein-2 and Zoledronic Acid Generates\nBone","volume":"6","author":"Raina","year":"2016","journal-title":"Sci. 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Steroid Biochem. Mol. Biol."},{"issue":"2","key":"2026081416130072100_cit34","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1166\/jbn.2013.1482","article-title":"Improvement\nin Bone Properties by Using Risedronate Adsorbed Hydroxyapatite Novel\nNanoparticle Based Formulation in a Rat Model of Osteoporosis","volume":"9","author":"Sahana","year":"2013","journal-title":"J. Biomed. Nanotechnol."},{"issue":"1","key":"2026081416130072100_cit35","doi-asserted-by":"publisher","first-page":"36","DOI":"10.2106\/JBJS.K.00668","article-title":"Intraosseous Injection\nof RhBMP-2\/Calcium Phosphate\nMatrix Improves Bone Structure and Strength in the Proximal Aspect\nof the Femur in Chronic Ovariectomized Nonhuman Primates","volume":"95","author":"Seeherman","year":"2013","journal-title":"J. Bone Jt. Surgery-American"},{"issue":"8","key":"2026081416130072100_cit36","doi-asserted-by":"publisher","first-page":"6816","DOI":"10.1021\/acsami.6b14782","article-title":"Nano-Hydroxyapatite\nBone Substitute Functionalized with Bone Active Molecules for Enhanced\nCranial Bone Regeneration","volume":"9","author":"Teotia","year":"2017","journal-title":"ACS Appl. Mater.\nInterfaces"},{"issue":"1","key":"2026081416130072100_cit37","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1021\/acsbiomaterials.8b00227","article-title":"Endogenous Platelet Rich Plasma Supplements\/Augments\nGrowth Factors Delivered via Porous Collagen-Nanohydroxyapatite Bone\nSubstitute for Enhanced Bone Formation","volume":"5","author":"Teotia","year":"2019","journal-title":"ACS\nBiomater. Sci. 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World J."},{"issue":"34","key":"2026081416130072100_cit42","doi-asserted-by":"publisher","first-page":"6941","DOI":"10.1016\/j.biomaterials.2005.04.059","article-title":"Effects\nof Bisphosphonates on Proliferation and Osteoblast Differentiation\nof Human Bone Marrow Stromal Cells","volume":"26","author":"von\nKnoch","year":"2005","journal-title":"Biomaterials"},{"issue":"3","key":"2026081416130072100_cit43","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0091317","article-title":"Controlled Delivery of Zoledronate Improved Bone Formation Locally\nIn Vivo","volume":"9","author":"Gou","year":"2014","journal-title":"PLoS One"},{"key":"2026081416130072100_cit44","volume-title":"Principles\nof Bone Biology","author":"Bilezikian","year":"2002","edition":"second"},{"issue":"3","key":"2026081416130072100_cit45","doi-asserted-by":"publisher","first-page":"468","DOI":"10.1359\/jbmr.081108","article-title":"Hip Fractures and the\nContribution of Cortical Versus Trabecular Bone to Femoral Neck Strength","volume":"24","author":"Holzer","year":"2009","journal-title":"J. Bone Miner. Res."}],"container-title":["Biomacromolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acs.biomac.9b01327","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/bomaf6\/article-pdf\/21\/2\/328\/5927113\/bm9b01327.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/bomaf6\/article-pdf\/21\/2\/328\/5927113\/bm9b01327.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T20:24:33Z","timestamp":1786739073000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/bomaf6\/article\/21\/2\/328\/591776\/Nanohydroxyapatite-Based-Ceramic-Carrier-Promotes"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,10,22]]},"references-count":45,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2019,10,22]]},"published-print":{"date-parts":[[2020,2,10]]}},"URL":"https:\/\/doi.org\/10.1021\/acs.biomac.9b01327","relation":{},"ISSN":["1525-7797","1526-4602"],"issn-type":[{"value":"1525-7797","type":"print"},{"value":"1526-4602","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,10,22]]}}}