Content-Dependent Osteogenic Response of Nanohydroxyapatite: An in Vitro and in Vivo Assessment within Collagen-Based Scaffolds
Abstract
The use of collagen-based scaffolds in orthopedic applications has been limited due to poor mechanical properties, but this may be overcome by the introduction of a stiffer supporting phase. Thus, we developed a synthesis technique to produce nonaggregating, stable nanohydroxyapatite (nHA) particles, permitting the fabrication of biomimetic-inspired scaffolds through the combination of nanosized HA with collagen, as found in native bone. This study evaluates the mechanical and biological impact of incorporating increasing concentrations of these nanoparticles into porous collagen scaffolds (1:1 and 5:1 weight ratios of nHA/collagen). Mechanical assessment demonstrated that increasing nHA incorporation correlated with increasing Young's moduli, which could be further amplified using cross-linking treatments. Typically, the porosity of a scaffold is sacrificed to produce a stiffer material; however, through the use of nanosized particles the inclusion of up to 5:1 nHA/collagen content still preserved the high 99% porosity of the composite scaffold, allowing for maximum cell infiltration. Moreover, increasing nHA presence induced significant bioactive responses, achieving superior cellular attachment and enhanced osteogenesis, promoting earlier expression of bone markers and cell-mediated mineralization versus nHA-free collagen controls. Interestingly, these content-dependent results observed in vitro did not directly translate in vivo. Instead, similar levels of bone formation were achieved within critical-sized rat calvarial defects, independent of nHA content, following acellular implantation. The addition of nHA, both 1:1 and 5:1, induced significantly higher levels of mineralization and de novo bone ingrowth versus collagen controls as demonstrated by microcomputed tomography, histological, and histomorphometric analyses. Ultimately, these results demonstrate the immense osteoinductivity of nonaggregated nanoparticles of HA incorporated into collagen-composite scaffolds and emphasize the importance of in vivo-based evaluation of therapies intended for clinical use.
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Structural and signaling molecules such as α 5 β 1 integrin and focal adhesion kinase that are important for bone formation easily interact with the -OH group of HA, leading to deposition of minerals.
“The structural, as well as signaling molecules such as α 5 β 1 integrin and focal adhesion kinase that are important for bone formation, easily interact with the -OH group of HA which in turn leads to the deposition of minerals [57].”
From Nano-hydroxyapatite/collagen composite as scaffold material for bone regeneration. (2023) · cites this paper as [57]
Cites
Matrix elasticity directs stem cell lineage specification
Engler, A. J., Sen, S., Sweeney, H. L., & Discher, D. E. (2006) · Cell · doi:10.1016/j.cell.2006.06.044 · Cited by 13,915 · see citing works
Langer, R., & Vacanti, J. P. (1993) · Science · doi:10.1126/science.8493529 · Cited by 9,893 · see citing works
Scaffolds in tissue engineering bone and cartilage
Hutmacher, D. W. (2000) · Biomaterials · doi:10.1016/s0142-9612(00)00121-6 · Cited by 5,002 · see citing works
Murphy, C. M., Haugh, M. G., & O’Brien, F. J. (2009) · Biomaterials · doi:10.1016/j.biomaterials.2009.09.063 · Cited by 2,057 · see citing works
Self-citationThe effect of pore size on cell adhesion in collagen-GAG scaffolds
O’Brien, F. J., Harley, B. A. C., Yannas, I. V., & Gibson, L. J. (2004) · Biomaterials · doi:10.1016/j.biomaterials.2004.02.052 · Cited by 1,336 · see citing works
Self-citationEnhanced functions of osteoblasts on nanophase ceramics
Webster, T. J. (2000) · Biomaterials · doi:10.1016/s0142-9612(00)00075-2 · Cited by 1,324 · see citing works
Wei, G., & Ma, P. X. (2004) · Biomaterials · doi:10.1016/j.biomaterials.2003.12.005 · Cited by 1,271 · see citing works
Nanotechnology and nanomaterials: Promises for improved tissue regeneration
Zhang, L. G., & Webster, T. J. (2008) · Nano Today · doi:10.1016/j.nantod.2008.10.014 · Cited by 1,147 · see citing works
Natural‐Based Nanocomposites for Bone Tissue Engineering and Regenerative Medicine: A Review
Pina, S., Oliveira, J. M., & Reis, R. L. (2015) · Advanced Materials · doi:10.1002/adma.201403354 · Cited by 945 · see citing works
Moutos, F. T., Freed, L. E., & Guilak, F. (2007) · Nature Materials · doi:10.1038/nmat1822 · Cited by 738 · see citing works
Keselowsky, B. G., Collard, D. M., & Garcı́a, A. J. (2004) · Biomaterials · doi:10.1016/j.biomaterials.2004.01.062 · Cited by 627 · see citing works
Kim, H., Kim, H.-E., & Salih, V. (2005) · Biomaterials · doi:10.1016/j.biomaterials.2005.01.047 · Cited by 451 · see citing works
O’Brien, F. J., Harley, B. A. C., Waller, M. A., Yannas, I. V., Gibson, L. J., & Prendergast, P. J. (2006) · Technology and Health Care · doi:10.3233/thc-2007-15102 · Cited by 368 · see citing works
Self-citationKong, L., Gao, Y., Lu, G., et al. (2006) · European Polymer Journal · doi:10.1016/j.eurpolymj.2006.08.009 · Cited by 331 · see citing works
Haugh, M. G., Murphy, C. M., McKiernan, R. C., Altenbuchner, C., & O’Brien, F. J. (2010) · Tissue Engineering Part A · doi:10.1089/ten.tea.2010.0590 · Cited by 330 · see citing works
Self-citationOsteoinduction by biomaterials—Physicochemical and structural influences
Habibović, P., Sees, T. M., van den Doel, M., et al. (2006) · Journal of Biomedical Materials Research Part A · doi:10.1002/jbm.a.30712 · Cited by 315 · see citing works
The collagen receptor integrins have distinct ligand recognition and signaling functions
Heino, J. (2000) · Matrix Biology · doi:10.1016/s0945-053x(00)00076-7 · Cited by 299 · see citing works
Haugh, M. G., Jaasma, M. J., & O’Brien, F. J. (2008) · Journal of Biomedical Materials Research Part A · doi:10.1002/jbm.a.31955 · Cited by 282 · see citing works
Self-citationGleeson, J. P., Plunkett, N., & O’Brien, F. J. (2010) · European Cells and Materials · doi:10.22203/ecm.v020a18 · Cited by 255 · see citing works
Self-citationKothapalli, C. R., Shaw, M. T., & Wei, M. (2005) · Acta Biomaterialia · doi:10.1016/j.actbio.2005.06.005 · Cited by 247 · see citing works
Lin, L., Chow, K. L., & Leng, Y. (2008) · Journal of Biomedical Materials Research Part A · doi:10.1002/jbm.a.31994 · Cited by 237 · see citing works
Farrell, E., O’Brien, F. J., Doyle, P. N., Fischer, J., Yannas, I. V., Harley, B. A. C., O'Connell, B. C., Prendergast, P. J., & Campbell, V. A. (2006) · Tissue Engineering · doi:10.1089/ten.2006.12.459 · Cited by 227 · see citing works
Self-citationLyons, F. G., Al-Munajjed, A. A., Kieran, S. M., Toner, M. E., Murphy, C. M., Duffy, G. P., & O’Brien, F. J. (2010) · Biomaterials · doi:10.1016/j.biomaterials.2010.08.056 · Cited by 222 · see citing works
Self-citationPolini, A., Pisignano, D., Parodi, M., Quarto, R., & Scaglione, S. (2011) · PLoS ONE · doi:10.1371/journal.pone.0026211 · Cited by 211 · see citing works
Curtin, C., Cunniffe, G., Lyons, F., Bessho, K., Dickson, G., Duffy, G., & O'Brien, F. (2012) · Advances in Materials · doi:10.1002/adma.201103828 · Cited by 204 · see citing works
Self-citation3D Scaffolds with Different Stiffness but the Same Microstructure for Bone Tissue Engineering
Chen, G., Dong, C., Yang, L., & Lv, Y. (2015) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.5b02662 · Cited by 204 · see citing works
Hydroxyapatite reinforced collagen scaffolds with improved architecture and mechanical properties
Kane, R. J., Weiss‐Bilka, H. E., Meagher, M. J., Liu, Y., Gargac, J. A., Niebur, G. L., Wagner, D. R., & Roeder, R. K. (2015) · Acta Biomaterialia · doi:10.1016/j.actbio.2015.01.031 · Cited by 202 · see citing works
Cunniffe, G. M., Dickson, G. R., Partap, S., Stanton, K. T., & O’Brien, F. J. (2010) · Journal of Materials Science: Materials in Medicine · doi:10.1007/s10856-009-3964-1 · Cited by 199 · see citing works
Self-citationThe Sequential Expression Profiles of Growth Factors from Osteroprogenitors to Osteoblasts In Vitro
Huang, Z., Nelson, E. R., Smith, R. L., et al. (2007) · Tissue Engineering · doi:10.1089/ten.2006.0423 · Cited by 197 · see citing works
Cell–scaffold mechanical interplay within engineered tissue
Rosenfeld, D., & Levenberg, S. (2009) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2009.02.001 · Cited by 170 · see citing works
Gao, X., Song, J., Ji, P., Zhang, X., Li, X., Xu, X., Wang, M., Zhang, S., Deng, Y., Deng, F., et al. (2016) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.5b12413 · Cited by 170 · see citing works
Curtin, C., Tierney, E. G., McSorley, K., Cryan, S., Duffy, G., & O'Brien, F. (2015) · Advanced Healthcare Materials · doi:10.1002/adhm.201400397 · Cited by 165 · see citing works
Self-citationRai, B., Lin, J., Lim, Z. X. H., Guldberg, R. E., Hutmacher, D. W., & Cool, S. M. (2010) · Biomaterials · doi:10.1016/j.biomaterials.2010.07.001 · Cited by 157 · see citing works
Wei, S., Deng, Y., Liu, X., Xu, A., Wang, L., Luo, Z., Zheng, Y., Deng, F., Tang, Z., & Wei, J. (2015) · International Journal of Nanomedicine · doi:10.2147/ijn.s75557 · Cited by 151 · see citing works
Osteoinduction of hydroxyapatite/β-tricalcium phosphate bioceramics in mice with a fractured fibula
Cheng, L., Ye, F., Yang, R., Lu, X., Shi, Y., Li, L., Fan, H., & Bu, H. (2009) · Acta Biomaterialia · doi:10.1016/j.actbio.2009.10.050 · Cited by 151 · see citing works
Zou, D., Zhang, Z., He, J., Zhang, K., Ye, D., Han, W., Zhou, J., Wang, Y., Li, Q., Liu, X., et al. (2011) · Biomaterials · doi:10.1016/j.biomaterials.2011.11.053 · Cited by 146 · see citing works
Nanotechnology for bone materials
Tran, N. L., & Webster, T. J. (2009) · Wiley Interdisciplinary Reviews Nanomedicine and Nanobiotechnology · doi:10.1002/wnan.23 · Cited by 141 · see citing works
Li, D., Sun, H., Jiang, L., Zhang, K., Liu, W., Zhu, Y., Fangteng, J., Shi, C., Zhao, L., Sun, H., et al. (2014) · ACS Applied Materials & Interfaces · doi:10.1021/am5017792 · Cited by 135 · see citing works
Osteoblasts respond to hydroxyapatite surfaces with immediate changes in gene expression
Xie, J., Baumann, M. J., & McCabe, L. R. (2004) · Journal of Biomedical Materials Research Part A · doi:10.1002/jbm.a.30140 · Cited by 134 · see citing works
Heo, S., Kim, S., Wei, J., Hyun, Y., Yun, H., Kim, D., Shin, J. W., & Shin, J. (2008) · Journal of Biomedical Materials Research Part A · doi:10.1002/jbm.a.31726 · Cited by 131 · see citing works
Adhesion of osteoblast-like cells on nanostructured hydroxyapatite
Okada, S., Ito, H., Nagai, A., Komotori, J., & Imai, H. (2009) · Acta Biomaterialia · doi:10.1016/j.actbio.2009.07.037 · Cited by 130 · see citing works
Rodrigues, S. C., Salgado, C. L., Sahu, A., Garcia, M. P., Fernandes, M. H., & Monteiro, F. J. (2013) · Journal of Biomedical Materials Research Part A · doi:10.1002/jbm.a.34394 · Cited by 127 · see citing works
Probing the Osteoinductive Effect of Calcium Phosphate by Using an In Vitro Biomimetic Model
Chai, Y. C., Roberts, S. J., Schrooten, J., et al. (2010) · Tissue Engineering Part A · doi:10.1089/ten.tea.2010.0160 · Cited by 127 · see citing works
Cunniffe, G. M., O’Brien, F. J., Partap, S., Levingstone, T. J., Stanton, K. T., & Dickson, G. R. (2010) · Journal of Biomedical Materials Research Part A · doi:10.1002/jbm.a.32931 · Cited by 106 · see citing works
Self-citationWebster, T. J., Siegel, R. W., & Bizios, R. (2001) · Scripta Materialia · doi:10.1016/s1359-6462(01)00873-9 · Cited by 105 · see citing works
Huang, Y., Zhou, G., Zheng, L., et al. (2012) · Nanoscale · doi:10.1039/c2nr12072k · Cited by 101 · see citing works
Raucci, M. G., D’Antò, V., Guarino, V., Sardella, E., Zeppetelli, S., Favia, P., & Ambrosio, L. (2010) · Acta Biomaterialia · doi:10.1016/j.actbio.2010.04.018 · Cited by 87 · see citing works
Ren, X., Bischoff, D. S., Weisgerber, D. W., Lewis, M. S., Tu, V., Yamaguchi, D. T., Miller, T. A., Harley, B. A. C., & Lee, J. C. (2015) · Biomaterials · doi:10.1016/j.biomaterials.2015.01.059 · Cited by 84 · see citing works
Characterization of nano hydroxyapatite/collagen surfaces and cellular behaviors
Zhu, X., Eibl, O., Scheideler, L., et al. (2006) · Journal of Biomedical Materials Research Part A · doi:10.1002/jbm.a.30706 · Cited by 81 · see citing works
Tsai, S., Hsu, F., & Chen, P. (2008) · Acta Biomaterialia · doi:10.1016/j.actbio.2008.03.015 · Cited by 70 · see citing works
Zan, X., Sitasuwan, P., Feng, S., et al. (2016) · Langmuir · doi:10.1021/acs.langmuir.5b04245 · Cited by 68 · see citing works
Li, M., Liu, W., Sun, J., Xianyu, Y., Wang, J., Zhang, W., Zheng, W., Huang, D., Di, S., Long, Y., et al. (2013) · ACS Applied Materials & Interfaces · doi:10.1021/am401937m · Cited by 62 · see citing works
Pramanik, S., Ataollahi, F., Pingguan‐Murphy, B., et al. (2015) · Scientific Reports · doi:10.1038/srep09806 · Cited by 61 · see citing works
Menard, C., Mitchell, S., & Spector, M. (2000) · Biomaterials · doi:10.1016/s0142-9612(00)00062-4 · Cited by 46 · see citing works
Yang, M., Zhou, G., Castano‐Izquierdo, H., et al. (2014) · Journal of Biomedical Nanotechnology · doi:10.1166/jbn.2015.2038 · Cited by 36 · see citing works
Collagen–hydroxyapatite composite scaffolds for tissue engineering
Liu, C. (2015) · Elsevier eBooks · doi:10.1016/b978-1-78242-033-0.00010-9 · Cited by 34 · see citing works
Liao, H.-T., Chen, Y.-Y., Lai, Y.-T., Hsieh, M., & Jiang, C. (2014) · BioMed Research International · doi:10.1155/2014/321549 · Cited by 34 · see citing works
Mechanical Properties of Glass-Ceramic A-W - Polyethylene Composites: Effect of Filler Content
Juhasz, J. A., Best, S. M., Kawashita, M., et al. (2003) · Key engineering materials · doi:10.4028/www.scientific.net/kem.240-242.947 · Cited by 4 · see citing works
Study of Hydroxyapatite Osteoinduction with Osteo-Specific Gene Expression of Stem Cells
Lin, L. W., Chow, K. L., & Leng, Y. (2007) · Key engineering materials · doi:10.4028/www.scientific.net/kem.361-363.1005 · Cited by 2 · see citing works
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Li, Z., Du, T., Ruan, C., & Niu, X. (2020) · Bioactive Materials · doi:10.1016/j.bioactmat.2020.11.004 · Cited by 274 · see citing works
Bittner, S. M., Smith, B. T., Díaz-Gómez, L. A., et al. (2019) · Acta Biomaterialia · doi:10.1016/j.actbio.2019.03.041 · Cited by 245 · see citing works
Ryan, E. J., Ryan, A. J., González‐Vázquez, A., Philippart, A., Ciraldo, F. E., Hobbs, C. J., Nicolosi, V., Boccaccini, A. R., Kearney, C. J., & O’Brien, F. J. (2019) · Biomaterials · doi:10.1016/j.biomaterials.2019.01.031 · Cited by 222 · see citing works
Self-citationFabrication, applications and challenges of natural biomaterials in tissue engineering
Ullah, S., & Chen, X. (2020) · Applied Materials Today · doi:10.1016/j.apmt.2020.100656 · Cited by 221 · see citing works
Fang, J., Li, P., Lu, X., Fang, L., Lü, X., & Ren, F. (2019) · Acta Biomaterialia · doi:10.1016/j.actbio.2019.02.019 · Cited by 207 · see citing works
Raftery, R., Castaño, I. M., Chen, G., Cavanagh, B., Quinn, B., Curtin, C., Cryan, S., & O'Brien, F. (2017) · Biomaterials · doi:10.1016/j.biomaterials.2017.09.036 · Cited by 113 · see citing works
Self-citationPore-forming bioinks to enable spatio-temporally defined gene delivery in bioprinted tissues
Gonzalez‐Fernandez, T., Rathan, S., Hobbs, C. J., et al. (2019) · Journal of Controlled Release · doi:10.1016/j.jconrel.2019.03.006 · Cited by 122 · see citing works
Self-citationCunniffe, G. M., Gonzalez‐Fernandez, T., Daly, A. C., Sathy, B. N., Jeon, O., Alsberg, E., & Kelly, D. J. (2017) · Tissue Engineering Part A · doi:10.1089/ten.tea.2016.0498 · Cited by 121 · see citing works
Self-citationSadowska, J. M., Genoud, K. J., Kelly, D. J., & O’Brien, F. J. (2021) · Materials Today · doi:10.1016/j.mattod.2020.12.018 · Cited by 112 · see citing works
Self-citationNaturally derived proteins and glycosaminoglycan scaffolds for tissue engineering applications
Celikkin, N., Rinoldi, C., Costantini, M., Trombetta, M., Rainer, A., & Święszkowski, W. (2017) · Materials Science and Engineering C · doi:10.1016/j.msec.2017.04.016 · Cited by 104 · see citing works
Barros, J., Melo, L. D. R., Araújo, R., et al. (2019) · Nanomedicine Nanotechnology Biology and Medicine · doi:10.1016/j.nano.2019.102145 · Cited by 97 · see citing works
Yu, W., Sun, T., Qi, C., Ding, Z., Zhao, H., Zhao, S., Shi, Z., Zhu, Y., Chen, D., & He, Y. (2017) · International Journal of Nanomedicine · doi:10.2147/ijn.s126505 · Cited by 89 · see citing works
Gonzalez‐Fernandez, T., Sathy, B. N., Hobbs, C. J., Cunniffe, G. M., McCarthy, H. O., Dunne, N., Nicolosi, V., O’Brien, F. J., & Kelly, D. J. (2017) · Acta Biomaterialia · doi:10.1016/j.actbio.2017.03.044 · Cited by 87 · see citing works
Self-citationYu, W., Sun, T., Qi, C., et al. (2017) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.6b12325 · Cited by 82 · see citing works
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Pitacco, P., Sadowska, J. M., O’Brien, F. J., & Kelly, D. J. (2022) · Acta Biomaterialia · doi:10.1016/j.actbio.2022.07.037 · Cited by 78 · see citing works
Self-citationYu, W., Sun, T., Ding, Z., Qi, C., Zhao, H., Chen, F., Shi, Z., Zhu, Y., Chen, D., & He, Y. (2017) · Journal of Materials Chemistry B · doi:10.1039/c6tb02747d · Cited by 75 · see citing works
Raftery, R. M., Castaño, I. M., Sperger, S., Chen, G., Cavanagh, B., Feichtinger, G. A., Redl, H. R., Hacobian, A., & O’Brien, F. J. (2018) · Journal of Controlled Release · doi:10.1016/j.jconrel.2018.05.022 · Cited by 74 · see citing works
Self-citationCurtin, C. M., Nolan, J., Conlon, R., Deneweth, L., Gallagher, C., Tan, Y. J., Cavanagh, B., Asraf, A. Z., Harvey, H. M., Miller-Delaney, S. F. C., et al. (2018) · Acta Biomaterialia · doi:10.1016/j.actbio.2018.02.004 · Cited by 72 · see citing works
Self-citationScaffold‐Based microRNA Therapies in Regenerative Medicine and Cancer
Curtin, C. M., Castaño, I. M., & O’Brien, F. J. (2017) · Advanced Healthcare Materials · doi:10.1002/adhm.201700695 · Cited by 69 · see citing works
Self-citationChen, Y., Zhu, R., Ke, Q., et al. (2017) · Nanoscale · doi:10.1039/c7nr00601b · Cited by 68 · see citing works
Sahebalzamani, M., Ziminska, M., McCarthy, H. O., Levingstone, T. J., Dunne, N., & Hamilton, A. (2022) · Biomaterials Science · doi:10.1039/d1bm01756j · Cited by 66 · see citing works
Recent development in multizonal scaffolds for osteochondral regeneration
Yu, L., Cavelier, S., Hannon, B., & Wei, M. (2023) · Bioactive Materials · doi:10.1016/j.bioactmat.2023.01.012 · Cited by 66 · see citing works
Díaz-Gómez, L. A., García‐González, C. A., Wang, J., Yang, F., Aznar‐Cervantes, S. D., Cenís, J. L., Reyes, R., Delgado, A., Évora, C., Concheiro, Á., et al. (2017) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2017.05.038 · Cited by 60 · see citing works
Natural protein bioinspired materials for regeneration of hard tissues
Xu, X., Chen, X., & Li, J. (2020) · Journal of Materials Chemistry B · doi:10.1039/d0tb00139b · Cited by 60 · see citing works
Nano-hydroxyapatite/collagen composite as scaffold material for bone regeneration.
Kavitha Sri, A., Arthi, C., Neya, N. R., & Hikku, G. S. (2023) · Biomedical Materials · doi:10.1088/1748-605x/acc99e · Cited by 57 · see citing works
Shalumon, K. T., Liao, H.-T., Kuo, C., Wong, C.-B., Li, C.-J., Mini, P. A., & Chen, J. (2019) · Materials Science and Engineering C · doi:10.1016/j.msec.2019.109855 · Cited by 57 · see citing works
Costard, L. S., Hosn, R. R., Ramanayake, H., O’Brien, F. J., & Curtin, C. M. (2021) · Acta Biomaterialia · doi:10.1016/j.actbio.2021.01.023 · Cited by 57 · see citing works
Self-citationSadowska, J. M., Power, R. N., Genoud, K. J., Matheson, A., González‐Vázquez, A., Costard, L. S., Eichholz, K. F., Pitacco, P., Hallegouet, T., Chen, G., et al. (2023) · Advanced Materials · doi:10.1002/adma.202307639 · Cited by 55 · see citing works
Self-citationKalirajan, C., & Thanikaivelan, P. (2020) · Advanced Healthcare Materials · doi:10.1002/adhm.202000247 · Cited by 53 · see citing works
Preclinical models for neuroblastoma: Advances and challenges
Nolan, J. C., Frawley, T., Tighe, J., Soh, H., Curtin, C. M., & Piskareva, O. (2020) · Cancer Letters · doi:10.1016/j.canlet.2020.01.015 · Cited by 52 · see citing works
Self-citationZhao, H., Tang, J., Zhou, D., Weng, Y., Qin, W., Liu, C., Lv, S., Wang, W., & Zhao, X. (2020) · International Journal of Nanomedicine · doi:10.2147/ijn.s238800 · Cited by 51 · see citing works
Bioinspired Collagen Scaffolds in Cranial Bone Regeneration: From Bedside to Bench
Lee, J. C., & Volpicelli, E. J. (2017) · Advanced Healthcare Materials · doi:10.1002/adhm.201700232 · Cited by 51 · see citing works
Castaño, I. M., Curtin, C. M., Duffy, G. P., & O’Brien, F. J. (2018) · Tissue Engineering Part A · doi:10.1089/ten.tea.2017.0460 · Cited by 48 · see citing works
Self-citationChen, M., Zhao, F., Li, Y., et al. (2019) · Materials Science and Engineering C · doi:10.1016/j.msec.2019.110153 · Cited by 43 · see citing works
Zhang, T., Chen, H., Zhang, Y., Zan, Y., Ni, T., Liu, M., & Pei, R. (2018) · Colloids and Surfaces B Biointerfaces · doi:10.1016/j.colsurfb.2018.11.050 · Cited by 42 · see citing works
Castaño, I. M., Raftery, R. M., Chen, G., Cavanagh, B., Quinn, B., Duffy, G. P., O’Brien, F. J., & Curtin, C. M. (2020) · Acta Biomaterialia · doi:10.1016/j.actbio.2020.03.042 · Cited by 42 · see citing works
Self-citationZhang, Y., Xiao, C., Huang, Y., et al. (2018) · RSC Advances · doi:10.1039/c8ra00383a · Cited by 41 · see citing works
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RetractedWijerathne, H. M. C. S., Yan, D. M., Zeng, B., et al. (2020) · SN Applied Sciences · doi:10.1007/s42452-020-2531-8 · Cited by 40 · see citing works
Growth plate extracellular matrix-derived scaffolds for large bone defect healing
Cunniffe, G., Díaz‐Payno, P. J., Ramey, J., Mahon, O. R., Dunne, A., Thompson, E., O’Brien, F. J., & Kelly, D. J. (2017) · European Cells and Materials · doi:10.22203/ecm.v033a10 · Cited by 40 · see citing works
Self-citationLin, R., Wang, Z., Li, Z., et al. (2022) · Materials Today Bio · doi:10.1016/j.mtbio.2022.100330 · Cited by 38 · see citing works
Simpson, C. R., Kelly, H. M., & Murphy, C. M. (2020) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2020.10.011 · Cited by 37 · see citing works
Costard, L. S., Kelly, D. C., Power, R. N., Hobbs, C. J., Jaśkaniec, S., Nicolosi, V., Cavanagh, B., Curtin, C. M., & O’Brien, F. J. (2020) · Pharmaceutics · doi:10.3390/pharmaceutics12121219 · Cited by 37 · see citing works
Self-citationPower, R. N., Cavanagh, B., Dixon, J. E., Curtin, C. M., & O’Brien, F. J. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23031460 · Cited by 35 · see citing works
Self-citationSong, T., Zhao, F., Wang, Y., Li, D., Lei, N., Li, X., Xiao, Y., & Zhang, X. (2021) · Journal of Materials Chemistry B · doi:10.1039/d0tb02648d · Cited by 34 · see citing works
Synergistic Effects of Controlled-Released BMP-2 and VEGF from nHAC/PLGAs Scaffold on Osteogenesis
Wang, T., Guo, S., & Zhang, H. (2018) · BioMed Research International · doi:10.1155/2018/3516463 · Cited by 33 · see citing works
Oltean‐Dan, D., Dogaru, G. B., Tomoaia-Cotişel, M., Apostu, D., Meşter, A., Benea, H. R. C., Păiuşan, M. G., Jianu, M. E., Mocanu, A., Balint, R., et al. (2019) · International Journal of Nanomedicine · doi:10.2147/ijn.s205880 · Cited by 32 · see citing works
Rivas, M., del Valle, L. J., Rodríguez-Rivero, A. M., et al. (2018) · ACS Biomaterials Science & Engineering · doi:10.1021/acsbiomaterials.8b00353 · Cited by 31 · see citing works
Jiang, J., Liu, X., Chen, H., Dai, C., Niu, X., Dai, L., Chen, X., & Zhang, S. (2020) · Biomaterials Science · doi:10.1039/d0bm01116a · Cited by 27 · see citing works
Ding, R., Liu, Y., Cheng, D., Yang, G., Wu, W., Du, H., Jin, X., Chen, Y., Wang, Y., Heng, B. C., et al. (2022) · Nano Research · doi:10.1007/s12274-022-4292-8 · Cited by 26 · see citing works
Castaño, I. M., Raftery, R. M., Chen, G., Cavanagh, B., Quinn, B., Duffy, G. P., Curtin, C. M., & O’Brien, F. J. (2023) · Acta Biomaterialia · doi:10.1016/j.actbio.2023.09.049 · Cited by 26 · see citing works
Self-citationBoller, L. A., Shiels, S. M., Florian, D. C., Peck, S. H., Schoenecker, J. G., Duvall, C. L., Wenke, J. C., & Guelcher, S. A. (2021) · Acta Biomaterialia · doi:10.1016/j.actbio.2021.05.056 · Cited by 25 · see citing works
Liu, X., Chang, Z., Chen, C., Liang, J., Shi, J., Xiu, F., Shao, Q., Meng, W.-W., Wang, J., & Li, X. (2022) · Stem Cell Research & Therapy · doi:10.1186/s13287-022-03208-0 · Cited by 26 · see citing works
Han, D., Wang, W., Gong, J., Ma, Y., & Li, Y. (2024) · Nanomedicine · doi:10.1080/17435889.2024.2375958 · Cited by 25 · see citing works
Kumar, P., Sharma, J., Kumar, R., Najser, J., Frantík, J., Manuja, A., Sunnam, N., & Praveenkumar, S. (2025) · Biomaterials Science · doi:10.1039/d4bm01606h · Cited by 25 · see citing works
Paiva, S. S., Ferreira, A., Pakenham, E., Kaur, K., Cavanagh, B., O’Brien, F. J., & Murphy, C. M. (2025) · Journal of Functional Biomaterials · doi:10.3390/jfb16100363 · Cited by 23 · see citing works
Self-citationAnghelescu, V. M., Neculae, I. I., Dincă, O. M., Vlădan, C., Socoliuc, C. G., Cioplea, M. D., Nichita, L., Popp, C. G., Zurac, S., & Bucur, A. (2018) · Journal of Immunology Research · doi:10.1155/2018/9349207 · Cited by 22 · see citing works
Zhao, H., Zhang, X., Zhou, D., Weng, Y., Qin, W., Pan, F., Lv, S., & Zhao, X. (2020) · Biomedical Materials · doi:10.1088/1748-605x/ab843f · Cited by 20 · see citing works
Yin, H., Li, X., Wang, P., et al. (2018) · Journal of Biomedical Materials Research Part A · doi:10.1002/jbm.a.36584 · Cited by 19 · see citing works
Dai, Z., Dang, M., Zhang, W., Sumathra, M., Teh, S. W., & Pan, H. (2019) · Artificial Cells Nanomedicine and Biotechnology · doi:10.1080/21691401.2019.1573183 · Cited by 19 · see citing works
Colaço, É., Brouri, D., Aissaoui, N., et al. (2019) · Biomacromolecules · doi:10.1021/acs.biomac.9b01299 · Cited by 18 · see citing works
Accelerating Bone Healing by Decorating BMP-2 on Porous Composite Scaffolds
Li, X., Yin, H., Luo, E., Zhu, S., Wang, P., Zhang, Z., Liao, G., Xu, J., Li, Z., & Li, J. (2019) · ACS Applied Bio Materials · doi:10.1021/acsabm.9b00761 · Cited by 18 · see citing works
Wang, L., Chen, X., Guo, R., Wang, S., Hong-tao, Z., Chen, F., & Xiao, J. (2024) · Chemical Engineering Journal · doi:10.1016/j.cej.2024.153297 · Cited by 17 · see citing works
Gao, Y., Tang, Z., Wu, Z., Zhang, J., Ma, J., Liu, S., & Wang, Y. (2025) · Biomaterials Science · doi:10.1039/d4bm01521e · Cited by 16 · see citing works
González‐Vázquez, A., Raftery, R. M., Günbay, S., Chen, G., Murray, D. J., & O’Brien, F. J. (2020) · Biomaterials · doi:10.1016/j.biomaterials.2020.120540 · Cited by 11 · see citing works
Self-citationRaftery, R. M., González‐Vázquez, A., Walsh, D. P., et al. (2024) · Advanced Healthcare Materials · doi:10.1002/adhm.202401031 · Cited by 10 · see citing works
Self-citationBiological Functions of Macromolecular Protein Hydrogels in Constructing Osteogenic Microenvironment
Wang, Y., Lv, H., Ren, S., Zhang, J., Liu, X., Chen, S., Zhai, J., & Zhou, Y. (2024) · ACS Biomaterials Science & Engineering · doi:10.1021/acsbiomaterials.4c00910 · Cited by 9 · see citing works
Optimizing the Delivery of mRNA to Mesenchymal Stem Cells for Tissue Engineering Applications
McCormick, K., Herrero, J. M., Haas, H., Fattah, S., Heise, A., O’Brien, F. J., & Cryan, S. (2024) · Molecular Pharmaceutics · doi:10.1021/acs.molpharmaceut.3c00898 · Cited by 10 · see citing works
Self-citationZhu, R., Chen, Y., Ke, Q., Zhang, C., & Guo, Y. (2017) · Materials & Design · doi:10.1016/j.matdes.2017.03.008 · Cited by 8 · see citing works
Sheehy, E. J., Coffey, N., Quigley, R. M., Duncan, H. F., Kennedy, O. D., & O’Brien, F. J. (2025) · Biomaterials · doi:10.1016/j.biomaterials.2025.123750 · Cited by 7 · see citing works
Self-citationBrady, R. T., O’Brien, F. J., & Hoey, D. A. (2022) · Bioengineering · doi:10.3390/bioengineering9010035 · Cited by 6 · see citing works
Self-citationHe, H., Wang, L., Cai, X., Wei, N., Wang, Q., & Xiao, J. (2024) · Applied Materials Today · doi:10.1016/j.apmt.2024.102060 · Cited by 6 · see citing works
Genoud, K. J., Sadowska, J. M., Power, R. N., et al. (2025) · Biofabrication · doi:10.1088/1758-5090/adaf59 · Cited by 4 · see citing works
Self-citationKnudsen, E.-E., Dreyer, C. H., Overgaard, S., et al. (2025) · Calcified Tissue International · doi:10.1007/s00223-024-01309-x · Cited by 3 · see citing works
ADVANCED NANOMATERIALS AND COATED SURFACES FOR ORTHOPEDIC IMPLANTS – A REVIEW
Balint, R., Mocanu, A., Tomoaia, G., Riga, S., & Tomoaia-Cotişel, M. (2021) · Annals of the Academy of Romanian Scientists Series on Physics and Chemistry · doi:10.56082/annalsarsciphyschem.2021.2.53 · Cited by 3 · see citing works
Biomimetic short fiber reinforced 3-dimensional scaffold for bone tissue regeneration
Sun, L., Liu, M., Li, Y., et al. (2024) · Biomedical Materials · doi:10.1088/1748-605x/ad2405 · Cited by 3 · see citing works
Four-muscle surgery for infantile esotropia with V-pattern.
Kraft, S. P., & Scott, W. E. (1986) · PubMed · Cited by 3 · see citing works
Liu, Y.-Y., Dobricic, M., Intini, C., O’Brien, F. J., LLorca, J., & Echeverry‐Rendón, M. (2025) · Colloids and Surfaces B Biointerfaces · doi:10.1016/j.colsurfb.2025.115354 · Cited by 2 · see citing works
Self-citationRunzer, C. D. T., Sadowska, J. M., Roumans, N. J. T., Plank, C., Evans, C. H., O’Brien, F. J., van Griensven, M., & Balmayor, E. R. (2025) · Advanced Functional Materials · doi:10.1002/adfm.202508631 · Cited by 2 · see citing works
Self-citationAn, L., Zhao, X., Xu, C., et al. (2019) · Russian Journal of Physical Chemistry A · doi:10.1134/s003602441907015x · Cited by 1 · see citing works
Nanoscale design in biomineralization for developing new biomaterials
Tavares, M. T., Farinha, J. P. S., Baleizão, C., & Mano, J. F. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-820508-2.00017-9 · Cited by 1 · see citing works
Castaño, I. M., Raftery, R. M., Curtin, C. M., Grillari, J., Redl, H. R., & O’Brien, F. J. (2020) · Springer eBooks · doi:10.1007/978-3-319-08831-0_34 · Cited by 1 · see citing works
Self-citationGonzalez‐Fernandez, T. (2018) · Arrow@dit (Dublin Institute of Technology)
Castaño, I. M., Raftery, R. M., Curtin, C. M., Grillari, J., Redl, H. R., & O’Brien, F. J. (2019) · Springer eBooks · doi:10.1007/978-3-319-37076-7_34-1
Self-citationVaithilingam, V., Reys, L. L., Sthijns, M. M. J. P. E., Rademakers, T., de Vries, R. H. W., Mohammed, S. G., Bont, D. D., Jetten, M., de Koning, E. J. P., Mourad, N. I., et al. (2022) · Tissue Engineering Part A · doi:10.1089/ten.tea.2022.29025.abstracts
A 3D scaffold of yak collagen-hydroxyapatite-sodium alginate for efficiently repairing bone defects
He, H., Wang, L., Cai, X., Li, W., & Xiao, J. (2023) · Scientia Sinica Chimica · doi:10.1360/ssc-2023-0043
Maretaningtias Dwi Ariani, H. P. (2023) · International Journal of Development Research · doi:10.37118/ijdr.26664.06.2023
Liu, X.-Y., Chang, Z.-H., Chen, C., Liang, J., Shi, J.-X., Fan, X., Shao, Q., Meng, W.-W., Wang, J.-J., & Li, X.-H. (2023) · Figshare · doi:10.6084/m9.figshare.22604758
Advances in bone repair scaffold research, from material properties and structural aspects
Cai, H., Liu, C., Song, W., Liu, Y., Qiao, A., & Du, T. (2026) · Journal of Materials Science · doi:10.1007/s10853-026-12464-x
Meyer, M., Jonsdottir, H. R., Amado, I., Gonzalez, J. G., Bracken, S., Kaur, K., Hodgkinson, T., Murray, D. J., O'Brien, F. J., & González-Vázquez, A. (2026) · Bioengineering · doi:10.3390/bioengineering13070746
Zhang, X., Wen, Y., Sun, Y., Hu, C., Li, X., Li, H., Fan, X., Liang, J., Chen, Y., & Fan, Y. (2026) · Chemical Engineering Journal · doi:10.1016/j.cej.2026.179192
Advanced functional biobased materials for stem cell-mediated regenerative therapy
Negi, S. S., Srivastava, U., Ahmad, F., et al. (2026) · Regenesis repair rehabilitation. · doi:10.1016/j.rerere.2026.07.004
Vasil’kov, A. Y., Voloshina, P. R., Naumkin, A. V., et al. (2026) · Russian Chemical Bulletin · doi:10.1007/s11172-026-5082-3
- Authors
- Cunniffe, G. M., Curtin, C. M., Thompson, E. M., Dickson, G. R., & O’Brien, F. J.
- Affiliations
- Royal College of Surgeons in Ireland (IE)
- Corresponding author
- O’Brien, Fergal J.
- Venue
- ACS Applied Materials & Interfaces
- Publisher
- American Chemical Society (ACS)
- Published
- 2016-08-30
- Volume
- 8
- Issue
- 36
- Pages
- 23477-23488
- ISSN
- 1944-8244 (ISSN-L)
- 1944-8252
- OpenAlex
- W2512953699
- Semantic Scholar
- 4aa91e34e45b3be2b778d5e66b8b3f51f2e25ca7
- Cited by
- 95
- References
- 59
- Citations by year
- 2026: 5 · 2025: 8 · 2024: 7 · 2023: 7 · 2022: 8 · 2021: 6 · 2020: 15 · 2019: 15 · 2018: 10 · 2017: 13
- FWCI
- 6.11
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- ACS Applied Materials & Interfaces (publishedVersion)
- PubMed (publishedVersion)
- Funders
- European Research Council (239685)
- Science Foundation Ireland (04/Yl1/B531, 06/RFP/ENM012, 11/RFP/ ENM/3063)
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › Bone Tissue Engineering Materials
- Physical Sciences › Materials Science › Biomaterials › Collagen: Extraction and Characterization
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Keywords
- hydroxyapatite nanoparticles, collagen scaffolds, osteogenic response, osteoinduction, bone tissue engineering, composite scaffolds, Young's modulus, crosslinking, porosity, cell attachment, mineralization, critical-size calvarial defect, bone ingrowth
- MeSH terms
- Animals, Bone Regeneration, Collagen, Osteogenesis, Porosity, Durapatite, Tissue Engineering, Rats, Tissue Scaffolds, X-Ray Microtomography
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