{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T23:12:19Z","timestamp":1793661139613,"version":"4.5.1"},"reference-count":61,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,9,29]],"date-time":"2021-09-29T00:00:00Z","timestamp":1632873600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Education Malaysia","award":["FRGS\/1\/2019\/STG05\/UKM\/02\/1"],"award-info":[{"award-number":["FRGS\/1\/2019\/STG05\/UKM\/02\/1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nanomaterials"],"abstract":"<jats:p>Nano-hydroxyapatite (nHA) has been widely used as an orthopedic biomaterial and vehicle for drug delivery owing to its chemical and structural similarity to bone minerals. Several studies have demonstrated that nHA based biomaterials have a potential effect for bone regeneration with very minimal to no toxicity or inflammatory response. This systematic review aims to provide an appraisal of the effectiveness of nHA as a delivery system for bone regeneration and whether the conjugation of proteins, antibiotics, or other bioactive molecules to the nHA further enhances osteogenesis in vivo. Out of 282 articles obtained from the literature search, only 14 articles met the inclusion criteria for this review. These studies showed that nHA was able to induce bone regeneration in various animal models with large or critical-sized bone defects, open fracture, or methicillin-resistant Staphylococcus aureus (MRSA)-induced osteomyelitis. The conjugations of drugs or bioactive molecules such as bone-morphogenetic protein-2 (BMP-2), vancomycin, calcitriol, dexamethasone, and cisplatin were able to enhance the osteogenic property of nHA. Thus, nHA is a promising delivery system for a variety of compounds in promoting bone regeneration in vivo.<\/jats:p>","DOI":"10.3390\/nano11102569","type":"journal-article","created":{"date-parts":[[2021,9,30]],"date-time":"2021-09-30T00:03:42Z","timestamp":1632960222000},"page":"2569","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":67,"title":["Nano-Hydroxyapatite as a Delivery System for Promoting Bone Regeneration In Vivo: A Systematic Review"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8417-4117","authenticated-orcid":false,"given":"Anis Syauqina","family":"Mohd Zaffarin","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine, Universiti Kebangsaan Malaysia, Bandar Tun Razak 56000, W.P. Kuala Lumpur, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiow-Fern","family":"Ng","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Kuala Lumpur 50300, W.P. Kuala Lumpur, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min Hwei","family":"Ng","sequence":"additional","affiliation":[{"name":"Centre for Tissue Engineering and Regenerative Medicine, Universiti Kebangsaan Malaysia, Bandar Tun Razak 56000, W.P. Kuala Lumpur, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haniza","family":"Hassan","sequence":"additional","affiliation":[{"name":"Department of Human Anatomy, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang 43400, Selangor, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0326-977X","authenticated-orcid":false,"given":"Ekram","family":"Alias","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine, Universiti Kebangsaan Malaysia, Bandar Tun Razak 56000, W.P. 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Chem. Bull."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1016\/j.jmatprotec.2007.10.004","article-title":"Preparation and bioactivity evaluation of bone-like hydroxyapatite nanopowder","volume":"202","author":"Fathi","year":"2008","journal-title":"J. Mater. Process. Technol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Ebrahimi, S., Nasri, C.S.S.M., and Bin Arshad, S.E. (2021). Hydrothermal synthesis of hydroxyapatite powders using Response Surface Methodology (RSM). PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0251009"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1007\/s10856-007-3156-9","article-title":"Synthesis of carbonated hydroxyapatite nanospheres through nanoemulsion","volume":"19","author":"Zhou","year":"2008","journal-title":"J. Mater. Sci. Mater. Med."},{"key":"ref_8","first-page":"437","article-title":"Sonochemical synthesis of hydroxyapatite and fluoroapatite nanosized bioceramics","volume":"13","author":"Barandehfard","year":"2012","journal-title":"J. Ceram. Process. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.bsecv.2017.05.001","article-title":"Calcium phosphates for biomedical applications","volume":"56","author":"Canillas","year":"2017","journal-title":"Bolet\u00edn De La Soc. Espa\u00f1ola De Cer\u00e1mica Y Vidr."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2007","DOI":"10.1002\/jbm.a.36395","article-title":"Gelatin\/nano-hydroxyapatite hydrogel scaffold prepared by sol-gel technology as filler to repair bone defects","volume":"106","author":"Raucci","year":"2018","journal-title":"J. Biomed. Mater. Res. A"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1016\/j.ijom.2010.01.013","article-title":"The repair of critical-size defects with porous hydroxyapatite\/polyamide nanocomposite: An experimental study in rabbit mandibles","volume":"39","author":"Zhang","year":"2010","journal-title":"Int. J. Oral Maxillofac. Surg."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1016\/j.surfcoat.2017.06.073","article-title":"MWCNT reinforced bone like calcium phosphate-hydroxyapatite composite coating developed through pulsed electrodeposition with varying amount of apatite phase and crystallinity to promote superior osteoconduction, cytocompatibility and corrosion protection performance compared to bare metallic implant surface","volume":"325","author":"Chakraborty","year":"2017","journal-title":"Surf. Coat. Technol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Harun, W.S.W., Asri, R.I.M., Sulong, A.B., Ghani, S.A.C., and Ghazalli, Z. (2018). Hydroxyapatite-based coating on biomedical implant. Hydroxyapatite: Advances in Composite Nanomaterials, Biomedical Applications and Its Technological Facets, IntechOpen.","DOI":"10.5772\/intechopen.71063"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e1504","DOI":"10.1002\/wnan.1504","article-title":"Recent progress on fabrication and drug delivery applications of nanostructured hydroxyapatite","volume":"10","author":"Mondal","year":"2018","journal-title":"Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1016\/j.ijpharm.2016.11.051","article-title":"Calcium phosphate nanoparticles functionalized with alendronate-conjugated polyethylene glycol (PEG) for the treatment of bone metastasis","volume":"516","author":"Chu","year":"2017","journal-title":"Int. J. Pharm."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1007\/s10856-011-4491-4","article-title":"A combined chitosan\/nano-size hydroxyapatite system for the controlled release of icariin","volume":"23","author":"Fan","year":"2012","journal-title":"J. Mater. Sci. Mater. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2769","DOI":"10.1016\/j.actbio.2011.03.019","article-title":"Nanoscale hydroxyapatite particles for bone tissue engineering","volume":"7","author":"Zhou","year":"2011","journal-title":"Acta Biomater."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2595","DOI":"10.1002\/jbm.a.36765","article-title":"Biomimetic hydroxyapatite as potential polymeric nanocarrier for the treatment of rheumatoid arthritis","volume":"107","author":"Ain","year":"2019","journal-title":"J. Biomed. Mater. Res. A"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Ghiasi, B., Sefidbakht, Y., and Rezaei, M. (2019). Hydroxyapatite for biomedicine and drug delivery. Nanomaterials for Advanced Biological Applications, Springer.","DOI":"10.1007\/978-3-030-10834-2_4"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1002\/adhm.201400397","article-title":"Combinatorial gene therapy accelerates bone regeneration: Non-viral dual delivery of VEGF and BMP2 in a collagen-nanohydroxyapatite scaffold","volume":"4","author":"Curtin","year":"2015","journal-title":"Adv. Healthc. Mater."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"100906","DOI":"10.1016\/j.apmt.2020.100906","article-title":"A multi-functionalized calcitriol sustainable delivery system for promoting osteoporotic bone regeneration both in vitro and in vivo","volume":"22","author":"Hu","year":"2021","journal-title":"Appl. Mater. Today"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"035030","DOI":"10.1088\/1748-605X\/abcae1","article-title":"A novel vertical aligned mesoporous silica coated nanohydroxyapatite particle as efficient dexamethasone carrier for potential application in osteogenesis","volume":"16","author":"Jia","year":"2021","journal-title":"Biomed. Mater."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1002\/jbm.a.31782","article-title":"Orthotopic bone formation by implantation of apatite-coated poly(lactide-co-glycolide)\/hydroxyapatite composite particulates and bone morphogenetic protein-2","volume":"87","author":"Kim","year":"2008","journal-title":"J. Biomed. Mater. Res. A"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2653","DOI":"10.1039\/D0BM00140F","article-title":"Biodegradable nanocomposite fibrous scaffold mediated local delivery of vancomycin for the treatment of MRSA infected experimental osteomyelitis","volume":"8","author":"Krishnan","year":"2020","journal-title":"Biomater. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2867","DOI":"10.1021\/acsbiomaterials.9b01574","article-title":"Synthesis and characterization of a biocomposite bone bandage for controlled delivery of bone-active drugs in fracture nonunions","volume":"6","author":"Raina","year":"2020","journal-title":"ACS Biomater. Sci. Eng."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1002\/term.463","article-title":"Repair of rat calvarial bone defects by controlled release of rhBMP-2 from an injectable bone regeneration composite","volume":"6","author":"Tan","year":"2012","journal-title":"J. Tissue Eng. Regen. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1007\/s11033-013-2876-9","article-title":"Dexamethasone-loaded hydroxyapatite enhances bone regeneration in rat calvarial defects","volume":"41","year":"2014","journal-title":"Mol. Biol. Rep."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"6816","DOI":"10.1021\/acsami.6b14782","article-title":"Nano-hydroxyapatite bone substitute functionalized with bone active molecules for enhanced cranial bone regeneration","volume":"9","author":"Teotia","year":"2017","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1007\/s00011-011-0402-x","article-title":"Vancomycin-loaded nano-hydroxyapatite pellets to treat MRSA-induced chronic osteomyelitis with bone defect in rabbits","volume":"61","author":"Jiang","year":"2012","journal-title":"Inflamm. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"495","DOI":"10.3233\/BME-161603","article-title":"The enhancement of osteogenic capacity in a synthetic BMP-2 derived peptide coated mineralized collagen composite in the treatment of the mandibular defects","volume":"27","author":"Lei","year":"2016","journal-title":"Bio-Med. Mater. Eng."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1900047","DOI":"10.1002\/mabi.201900047","article-title":"An injectable, bifunctional hydrogel with photothermal effects for tumor therapy and bone regeneration","volume":"19","author":"Luo","year":"2019","journal-title":"Macromol. Biosci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"12714","DOI":"10.3390\/ijms140612714","article-title":"Dual delivery of BMP-2 and bFGF from a new nano-composite scaffold, loaded with vascular stents for large-size mandibular defect regeneration","volume":"14","author":"Su","year":"2013","journal-title":"Int. J. Mol. Sci."},{"key":"ref_33","first-page":"29","article-title":"Development of a novel biomaterial, hydroxyapatite\/collagen (HAp\/Col) composite for medical use","volume":"15","author":"Itoh","year":"2005","journal-title":"Biomed. Mater. Eng."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2041731415609448","DOI":"10.1177\/2041731415609448","article-title":"Bisphosphonate-adsorbed ceramic nanoparticles increase bone formation in an injectable carrier for bone tissue engineering","volume":"6","author":"Cheng","year":"2015","journal-title":"J. Tissue Eng."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2922","DOI":"10.1038\/s41598-017-03086-0","article-title":"The shape and size of hydroxyapatite particles dictate inflammatory responses following implantation","volume":"7","author":"Lebre","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"4083","DOI":"10.2147\/IJN.S158280","article-title":"Loading BMP-2 on nanostructured hydroxyapatite microspheres for rapid bone regeneration","volume":"13","author":"Zhou","year":"2018","journal-title":"Int. J. Nanomed."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1177\/0300985815593124","article-title":"Animal models for evaluation of bone implants and devices: Comparative bone structure and common model uses","volume":"52","author":"Wancket","year":"2015","journal-title":"Vet. Pathol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1186\/s12951-015-0099-z","article-title":"Nanohydroxyapatite-reinforced chitosan composite hydrogel for bone tissue repair in vitro and in vivo","volume":"13","author":"Dhivya","year":"2015","journal-title":"J. Nanobiotechnol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"6758","DOI":"10.1016\/j.biomaterials.2014.04.085","article-title":"Polyetheretherketone\/nano-fluorohydroxyapatite composite with antimicrobial activity and osseointegration properties","volume":"35","author":"Wang","year":"2014","journal-title":"Biomaterials"},{"key":"ref_40","first-page":"401","article-title":"Bioactive hydrogels for bone regeneration","volume":"3","author":"Bai","year":"2018","journal-title":"Bioact. Mater."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.gendis.2014.07.005","article-title":"Bone Morphogenetic Protein (BMP) signaling in development and human diseases","volume":"1","author":"Wang","year":"2014","journal-title":"Genes Dis."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Heubel, B., and Nohe, A. (2021). The role of BMP signaling in osteoclast regulation. J. Dev. Biol., 9.","DOI":"10.3390\/jdb9030024"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1016\/j.addr.2012.03.014","article-title":"Studies of bone morphogenetic protein-based surgical repair","volume":"64","author":"Lo","year":"2012","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_44","unstructured":"Young Jae, M., Seongyup, J., and Kwang-Bok, L. (2021). BMP-2 promotes bone formation in bone defects in which bone remodeling is suppressed by long-term and high-dose zoledronic acid. Res. Sq."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1202159","DOI":"10.1155\/2019\/1202159","article-title":"Nanocrystalline Hydroxyapatite-Based Scaffold Adsorbs and Gives Sustained Release of Osteoinductive Growth Factor and Facilitates Bone Regeneration in Mice Ectopic Model","volume":"2019","author":"Zhou","year":"2019","journal-title":"J. Nanomater."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2816","DOI":"10.1016\/j.biomaterials.2009.01.031","article-title":"Effect of local sequential VEGF and BMP-2 delivery on ectopic and orthotopic bone regeneration","volume":"30","author":"Kempen","year":"2009","journal-title":"Biomaterials"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1086","DOI":"10.1002\/jor.23287","article-title":"Dual growth factor delivery from biofunctionalized allografts: Sequential VEGF and BMP-2 release to stimulate allograft remodeling","volume":"35","author":"Sharmin","year":"2017","journal-title":"J. Orthop. Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2869572","DOI":"10.1155\/2016\/2869572","article-title":"Synergistic Effects of Vascular Endothelial Growth Factor on Bone Morphogenetic Proteins Induced Bone Formation In Vivo: Influencing Factors and Future Research Directions","volume":"2016","author":"Li","year":"2016","journal-title":"BioMed Res. Int."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"4483","DOI":"10.3892\/mmr.2017.7183","article-title":"Synergistic effects of fibroblast growth factor-2 and bone morphogenetic protein-2 on bone induction","volume":"16","author":"Song","year":"2017","journal-title":"Mol. Med. Rep."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"115390","DOI":"10.1016\/j.bone.2020.115390","article-title":"Zoledronate","volume":"137","author":"Reid","year":"2020","journal-title":"Bone"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2309499018802487","DOI":"10.1177\/2309499018802487","article-title":"Bisphosphonates reduce biomaterial turnover in healing of critical-size rat femoral defects","volume":"26","author":"Hauser","year":"2018","journal-title":"J. Orthop. Surg."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"5829","DOI":"10.1158\/1078-0432.CCR-09-0426","article-title":"High-dose zoledronic acid impacts bone remodeling with effects on osteoblastic lineage and bone mechanical properties","volume":"15","author":"Pozzi","year":"2009","journal-title":"Clin. Cancer Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"28537","DOI":"10.1038\/srep28537","article-title":"Effects of local delivery of BMP2, zoledronate and their combination on bone microarchitecture, biomechanics and bone turnover in osteoporotic rabbits","volume":"6","author":"Jing","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.jor.2016.10.004","article-title":"Osteomyelitis: Recent advances in pathophysiology and therapeutic strategies","volume":"14","author":"Birt","year":"2017","journal-title":"J. Orthop."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.msec.2013.12.038","article-title":"Preparation and characterization of antimicrobial nano-hydroxyapatite composites","volume":"37","author":"Yu","year":"2014","journal-title":"Mater. Sci. Eng. C"},{"key":"ref_56","first-page":"CD000227","article-title":"Vitamin D and vitamin D analogues for preventing fractures in post-menopausal women and older men","volume":"2014","author":"Avenell","year":"2014","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_57","first-page":"515","article-title":"Management of osteoporosis with calcitriol in elderly Chinese patients: A systematic review","volume":"9","author":"Liao","year":"2014","journal-title":"Clin. Interv. Aging"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.msec.2014.12.064","article-title":"Local administration of calcitriol positively influences bone remodeling and maturation during restoration of mandibular bone defects in rats","volume":"49","author":"Liu","year":"2015","journal-title":"Mater. Sci. Eng. C"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ijpharm.2016.04.032","article-title":"The synergistic effect of nano-hydroxyapatite and dexamethasone in the fibrous delivery system of gelatin and poly(l-lactide) on the osteogenesis of mesenchymal stem cells","volume":"507","author":"Amjadian","year":"2016","journal-title":"Int. J. Pharm."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"101963","DOI":"10.1016\/j.jddst.2020.101963","article-title":"Effect of curcumin sorbed selenite substituted hydroxyapatite on osteosarcoma cells: An in vitro study","volume":"60","author":"Dhatchayani","year":"2020","journal-title":"J. Drug Deliv. Sci. Technol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"9825073","DOI":"10.1155\/2020\/9825073","article-title":"Strontium\/chitosan\/hydroxyapatite\/norcantharidin composite that inhibits osteosarcoma and promotes osteogenesis in vitro","volume":"2020","author":"Huang","year":"2020","journal-title":"BioMed Res. 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