A biocomposite of collagen nanofibers and nanohydroxyapatite for bone regeneration
Open accessAbstract
This work aims to design a synthetic construct that mimics the natural bone extracellular matrix through innovative approaches based on simultaneous type I collagen electrospinning and nanophased hydroxyapatite (nanoHA) electrospraying using non-denaturating conditions and non-toxic reagents. The morphological results, assessed using scanning electron microscopy and atomic force microscopy (AFM), showed a mesh of collagen nanofibers embedded with crystals of HA with fiber diameters within the nanometer range (30 nm), thus significantly lower than those reported in the literature, over 200 nm. The mechanical properties, assessed by nanoindentation using AFM, exhibited elastic moduli between 0.3 and 2 GPa. Fourier transformed infrared spectrometry confirmed the collagenous integrity as well as the presence of nanoHA in the composite. The network architecture allows cell access to both collagen nanofibers and HA crystals as in the natural bone environment. The inclusion of nanoHA agglomerates by electrospraying in type I collagen nanofibers improved the adhesion and metabolic activity of MC3T3-E1 osteoblasts. This new nanostructured collagen-nanoHA composite holds great potential for healing bone defects or as a functional membrane for guided bone tissue regeneration and in treating bone diseases.
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The higher metabolic activity of the nano-HA incorporated scaffold was because calcium ions released from nano-HA promote and stimulate adhesion of bone cells and subsequent activity.
“This was because of the release of calcium ions from nano-HA that promote and stimulate the adhesion of bone cells and subsequent activity.”
From Nano-hydroxyapatite/collagen composite as scaffold material for bone regeneration. (2023) · cites this paper as [8]
Section 3.2 reports higher metabolic activity on the collagen–nanoHA constructs and says calcium ions “seem to promote” bone-cell adhesion and subsequent activity. It does not establish that calcium ions were released from the nanoHA or that their release caused the higher activity; the citing sentence presents that tentative explanation as fact. Page numbers are unavailable in our copy. (LLM, conf=0.87)
Experimental — accuracy not yet measuredElectrospraying nano-HA over collagen fibers led to the formation of a hierarchical structure.
“Simultaneously, nano-HA was electro-sprayed over the collagen fibers with a 20 kV electrostatic field (figure 5(c)) leading to the formation of a hierarchical structure.”
From Nano-hydroxyapatite/collagen composite as scaffold material for bone regeneration. (2023) · cites this paper as [8]
The scaffold's unique structure enabled cell accessibility in a manner similar to that occurring in natural bone.
“The scaffold's unique structure enabled cell accessibility in a manner similar to that occurring in the natural bone.”
From Nano-hydroxyapatite/collagen composite as scaffold material for bone regeneration. (2023) · cites this paper as [8]
Ribeiro et al. successfully fabricated a nano-HA/collagen scaffold for bone regeneration using simultaneous electrospinning and electrospraying.
“Ribeiro et al [8] successfully fabricated a nano-HA/collagen scaffold for bone regeneration using simultaneous electrospinning and electrospraying method.”
From Nano-hydroxyapatite/collagen composite as scaffold material for bone regeneration. (2023) · cites this paper as [8]
The metabolic activity of pure collagen scaffold was less than that of the nano-HA incorporated scaffold.
“The metabolic activity of the pure collagen scaffold was less than the metabolic activity of the nano-HA incorporated scaffold.”
From Nano-hydroxyapatite/collagen composite as scaffold material for bone regeneration. (2023) · cites this paper as [8]
The prepared collagen fibers displayed a three-dimensional network morphology.
“The morphology of the prepared collagen fibers displayed a threedimensional network (figure 5(b)).”
From Nano-hydroxyapatite/collagen composite as scaffold material for bone regeneration. (2023) · cites this paper as [8]
Cells cultured on nano-HA/collagen structure were able to interact with both organic and inorganic phases.
“From the figure, it was clear that the cells over the nano-HA/collagen structure were able to interact with both organic and inorganic phases.”
From Nano-hydroxyapatite/collagen composite as scaffold material for bone regeneration. (2023) · cites this paper as [8]
Cells completely fused within the scaffold surface, making it difficult to distinguish between the cells and the scaffold.
“Moreover, the cells completely fused within the scaffold surface making it difficult to distinguish between the cells and the scaffold.”
From Nano-hydroxyapatite/collagen composite as scaffold material for bone regeneration. (2023) · cites this paper as [8]
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Cites
Foreign body reaction to biomaterials
Anderson, J. M., Rodriguez, A., & Chang, D. T. (2008) · Seminars in Immunology · doi:10.1016/j.smim.2007.11.004 · Cited by 5,138 · cited 1× · see citing works
“may cause clinical problems [23, 24].”
Electrospinning: A fascinating fiber fabrication technique
Bhardwaj, N., & Kundu, S. C. (2010) · Biotechnology Advances · doi:10.1016/j.biotechadv.2010.01.004 · Cited by 5,054 · see citing works
Electrospinning of Collagen Nanofibers
Matthews, J. A., Wnek, G. E., Simpson, D. G., & Bowlin, G. L. (2002) · Biomacromolecules · doi:10.1021/bm015533u · Cited by 2,253 · see citing works
Nanotechnology in Drug Delivery and Tissue Engineering: From Discovery to Applications
Shi, J., Votruba, A. R., Farokhzad, O. C., & Langer, R. (2010) · Nano Letters · doi:10.1021/nl102184c · Cited by 1,620 · see citing works
Journal of Biomedical Materials Research Part A
(2006) · Journal of Biomedical Materials Research Part A · doi:10.1002/(issn)1552-4965 · Cited by 749 · see citing works
Collagen-Hydroxyapatite Composites for Hard Tissue Repair
Wahl, D. A., & Czernuszka, J. (2006) · European Cells and Materials · doi:10.22203/ecm.v011a06 · Cited by 676 · see citing works
Electrospinning of collagen and elastin for tissue engineering applications
Buttafoco, L., Kolkman, N. G., Engbers‐Buijtenhuijs, P., Poot, A. A., Dijkstra, P. J., Vermes, I., & Feijen, J. (2005) · Biomaterials · doi:10.1016/j.biomaterials.2005.06.024 · Cited by 628 · see citing works
Choi, J. S., Lee, S. J., Christ, G. J., Atala, A., & Yoo, J. J. (2008) · Biomaterials · doi:10.1016/j.biomaterials.2008.03.031 · Cited by 611 · see citing works
Mechanical Properties of Collagen Fibrils
Wenger, M. P. E., Bozec, L., Horton, M. A., & Mesquida, P. (2007) · Biophysical Journal · doi:10.1529/biophysj.106.103192 · Cited by 564 · see citing works
FT-IR study for hydroxyapatite/collagen nanocomposite cross-linked by glutaraldehyde
Chang, M. C., & Tanaka, J. (2002) · Biomaterials · doi:10.1016/s0142-9612(02)00232-6 · Cited by 560 · see citing works
Chen, Z. G., Wang, P. W., Wei, B., Mo, X. M., & Cui, F. (2009) · Acta Biomaterialia · doi:10.1016/j.actbio.2009.07.024 · Cited by 380 · see citing works
Zhong, S., Teo, W. E., Zhu, X., Beuerman, R. W., Ramakrishna, S., & Yung, L. Y. L. (2006) · Journal of Biomedical Materials Research Part A · doi:10.1002/jbm.a.30870 · Cited by 341 · see citing works
Gupta, D., Venugopal, J. R., Mitra, S., Dev, V. R. G., & Ramakrishna, S. (2009) · Biomaterials · doi:10.1016/j.biomaterials.2008.12.079 · Cited by 317 · see citing works
Immobilization of heparin to EDC/NHS-crosslinked collagen. Characterization and in vitro evaluation
Wissink, M., Beernink, R. H. J., Pieper, J., Poot, A. A., Engbers, G. H. M., Beugeling, T., van Aken, W. G., & Feijén, J. (2001) · Biomaterials · doi:10.1016/s0142-9612(00)00164-2 · Cited by 313 · see citing works
Mechanical properties of single electrospun collagen type I fibers
Yang, L., Fitié, C. F. C., van der Werf, K. O., Bennink, M. L., Dijkstra, P. J., & Feijén, J. (2007) · Biomaterials · doi:10.1016/j.biomaterials.2007.10.058 · Cited by 291 · see citing works
Intermolecular interactions in electrospun collagen–chitosan complex nanofibers
Chen, Z., Mo, X., He, C., et al. (2007) · Carbohydrate Polymers · doi:10.1016/j.carbpol.2007.09.018 · Cited by 285 · see citing works
Electrospun PLGA/collagen nanofibrous membrane as early-stage wound dressing
Liu, S., Kau, Y., Chou, C.-Y., Chen, J., Wu, R., & Yeh, W. (2010) · Journal of Membrane Science · doi:10.1016/j.memsci.2010.03.012 · Cited by 254 · see citing works
Electrospinning of Collagen Nanofiber Scaffolds from Benign Solvents
Dong, B., Arnoult, O., Smith, M., & Wnek, G. E. (2009) · Macromolecular Rapid Communications · doi:10.1002/marc.200800634 · Cited by 228 · see citing works
Chen, R., Huang, C., Ke, Q., et al. (2010) · Colloids and Surfaces B Biointerfaces · doi:10.1016/j.colsurfb.2010.03.043 · Cited by 218 · 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
Production of electrospun gelatin nanofiber by water-based co-solvent approach
Song, J., Kim, H., & Kim, H. (2007) · Journal of Materials Science Materials in Medicine · doi:10.1007/s10856-007-3169-4 · Cited by 198 · see citing works
Al-Munajjed, A. A., Plunkett, N. A., Gleeson, J. P., Weber, T., Jungreuthmayer, C., Levingstone, T. J., Hammer, J., & O’Brien, F. J. (2009) · Journal of Biomedical Materials Research Part B Applied Biomaterials · doi:10.1002/jbm.b.31320 · Cited by 197 · see citing works
Mineralization of osteoblasts with electrospun collagen/hydroxyapatite nanofibers
Venugopal, J. R., Low, S., Choon, A. T., Kumar, T. S. S., & Ramakrishna, S. (2007) · Journal of Materials Science Materials in Medicine · doi:10.1007/s10856-007-3289-x · Cited by 185 · see citing works
Cytocompatibility of chitosan and collagen-chitosan scaffolds for tissue engineering
Fernandes, L. L., Resende, C. X., Tavares, D. D. S., et al. (2011) · Polímeros · doi:10.1590/s0104-14282011005000008 · Cited by 171 · see citing works
Järvinen, T. A. H., Järvinen, T. L. N., Kannus, P., Józsa, L., & Järvinen, M. (2004) · Journal of Orthopaedic Research® · doi:10.1016/j.orthres.2004.04.003 · Cited by 156 · see citing works
The uptake of titanium ions by hydroxyapatite particles-structural changes and possible mechanisms.
Ribeiro, C., Gibson, I., & Barbosa, M. (2006) · Biomaterials · doi:10.1016/j.biomaterials.2005.09.043 · Cited by 151 · see citing works
Biomaterial based cardiac tissue engineering and its applications
Huyer, L. D., Montgomery, M., Zhao, Y., Xiao, Y., Conant, G., Korolj, A., & Radisic, M. (2015) · Biomedical Materials · doi:10.1088/1748-6041/10/3/034004 · Cited by 145 · see citing works
Determination of the elastic modulus of native collagen fibrils via radial indentation
Heim, A. J., Matthews, W. G., & Koob, T. J. (2006) · Applied Physics Letters · doi:10.1063/1.2367660 · Cited by 142 · see citing works
Crosslinking of collagen with dendrimers
Duan, X., & Sheardown, H. D. (2005) · Journal of Biomedical Materials Research Part A · doi:10.1002/jbm.a.30475 · Cited by 128 · see citing works
Electrospinning of silk fibroin and collagen for vascular tissue engineering
Zhou, J., Cao, C., Ma, X., et al. (2010) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2010.07.010 · Cited by 121 · see citing works
Liu, T., Teng, W. K., Chan, B. P., et al. (2010) · Journal of Biomedical Materials Research Part A · doi:10.1002/jbm.a.32831 · Cited by 104 · see citing works
Francis, L., Venugopal, J. R., Prabhakaran, M. P., Thavasi, V., Marsano, E., & Ramakrishna, S. (2010) · Acta Biomaterialia · doi:10.1016/j.actbio.2010.05.001 · Cited by 99 · see citing works
Collagen/hydroxyapatite composite nanofibers by electrospinning
Teng, S.-H., Lee, E.-J., Wang, P., & Kim, H.-E. (2008) · Materials Letters · doi:10.1016/j.matlet.2008.01.104 · Cited by 98 · see citing works
Song, W., Markel, D. C., Wang, S., Shi, T., Mao, G., & Ren, W. (2012) · Nanotechnology · doi:10.1088/0957-4484/23/11/115101 · Cited by 96 · see citing works
Electrospun PLGA–silk fibroin–collagen nanofibrous scaffolds for nerve tissue engineering
Wang, G., Hu, X., Wei, L., Dong, C., & Wu, H. (2010) · In Vitro Cellular & Developmental Biology - Animal · doi:10.1007/s11626-010-9381-4 · Cited by 96 · see citing works
Development of a novel collagen–GAG nanofibrous scaffold via electrospinning
Zhong, S. P., Teo, W. E., Zhu, X., Beuerman, R. W., Ramakrishna, S., & Yung, L. Y. L. (2006) · Materials Science and Engineering C · doi:10.1016/j.msec.2006.05.010 · Cited by 90 · see citing works
The mechanical stress–strain properties of single electrospun collagen type I nanofibers
Carlisle, C. R., Coulais, C., & Guthold, M. (2010) · Acta Biomaterialia · doi:10.1016/j.actbio.2010.02.050 · Cited by 86 · see citing works
Microfabricated Electrospun Collagen Membranes for 3-D Cancer Models and Drug Screening Applications
Hartman, O., Zhang, C., Adams, E. L., et al. (2009) · Biomacromolecules · doi:10.1021/bm8012764 · Cited by 72 · see citing works
Hild, N., Schneider, O., Mohn, D., Luechinger, N. A., Koehler, F. M., Hofmann, S., Vetsch, J. R., Thimm, B. W., Müller, R., & Stark, W. J. (2010) · Nanoscale · doi:10.1039/c0nr00615g · Cited by 66 · see citing works
In vivo evaluation of highly macroporous ceramic scaffolds for bone tissue engineering
Teixeira, S., Fernandes, H., Leusink, A., et al. (2009) · Journal of Biomedical Materials Research Part A · doi:10.1002/jbm.a.32532 · Cited by 62 · see citing works
EDC/NHS cross-linked collagen foams as scaffolds for artificial corneal stroma
Vrana, N. E., Builles, N., Kocak, H., et al. (2007) · Journal of Biomaterials Science Polymer Edition · doi:10.1163/156856207794761961 · Cited by 57 · see citing works
Poly(vinyl alcohol)/collagen/hydroxyapatite hydrogel: Properties and in vitro cellular response
Wei, S., Markel, D. C., Jin, X., et al. (2012) · Journal of Biomedical Materials Research Part A · doi:10.1002/jbm.a.34240 · Cited by 54 · see citing works
Easy preparation of SnO2@carbon composite nanofibers with improved lithium ion storage properties
Yang, Z., Du, G., Guo, Z., et al. (2010) · Journal of materials research/Pratt's guide to venture capital sources · doi:10.1557/jmr.2010.0194 · Cited by 54 · see citing works
Cao, D., Wu, Y., Fu, Z., Tian, Y., Li, C., Gao, C., Chen, Z., & Feng, X. (2010) · Colloids and Surfaces B Biointerfaces · doi:10.1016/j.colsurfb.2010.12.005 · Cited by 50 · see citing works
Heparinized hydroxyapatite/collagen three-dimensional scaffolds for tissue engineering
Teixeira, S., Yang, L., Dijkstra, P. J., et al. (2010) · Journal of Materials Science Materials in Medicine · doi:10.1007/s10856-010-4097-2 · Cited by 46 · see citing works
A novel amperometric hydrogen peroxide biosensor based on electrospun Hb–collagen composite
Guo, F., Xu, X., Sun, Z., et al. (2011) · Colloids and Surfaces B Biointerfaces · doi:10.1016/j.colsurfb.2011.03.032 · Cited by 44 · see citing works
Phase ordering in blend films of semi-crystalline and amorphous polymers
Ferreiro, V., Douglas, J. F., & Amis, E. J. (2001) · Macromolecular Symposia · doi:10.1002/1521-3900(200103)167:1 · Cited by 32 · see citing works
Novel Biologically Inspired Collagen Nanofibers Reconstituted by Electrospinning Method
Foltran, I., Foresti, E., Parma, B., et al. (2008) · Macromolecular Symposia · doi:10.1002/masy.200850914 · Cited by 31 · see citing works
Dawes, E., & Rushton, N. (1994) · Clinical Materials · doi:10.1016/0267-6605(94)90031-0 · Cited by 19 · see citing works
Sharp burnout failure observed in high current-carrying double-walled carbon nanotube fibers
Song, L., Tóth, G., Wei, J., Liu, Z., Gao, W., Ci, L., Vajtai, R., Endo, M., & Ajayan, P. M. (2011) · Nanotechnology · doi:10.1088/0957-4484/23/1/015703 · Cited by 15 · see citing works
Preparation and Characterization of Calcium Phosphate Nanoparticles
Manuel, C. M., Foster, M., Monteiro, F. J., et al. (2003) · Key engineering materials · doi:10.4028/www.scientific.net/kem.254-256.903 · Cited by 9 · see citing works
Self-citationMicrofabricated Electrospun Collagen Membranes for 3-D Cancer Models and Drug Screening Applications
Hartman, O., Zhang, C., Adams, E. L., et al. (2009) · Biomacromolecules · doi:10.1021/bm900911a · Cited by 5 · see citing works
Electro-spinning of pure collagen nano-fibres–just an expensive way to make gelatin?
Zeugolis, D. I., Khew, S. T., Yew, E. S. Y., Ekaputra, A. K., Tong, Y. W., Yung, L.-Y. L., Hutmacher, D. W., Sheppard, C., & Raghunath, M. (2008) · Biomaterials · doi:10.1016/j.biomaterials.2008.02.009 · Cited by 1 · see citing works
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Nanosized CaP-silk fibroin-PCL-PEG-PCL/PCL based bilayer membranes for guided bone regeneration
Türkkan, S., Pazarçeviren, A. E., Keskin, D., Machin, N. E., Duygulu, Ö., & Tezcaner, A. (2017) · Materials Science and Engineering: C · doi:10.1016/j.msec.2017.06.016 · Cited by 75 · 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
- Authors
- Ribeiro, N., Sousa, S. R., van Blitterswijk, C. A., Moroni, L., & Monteiro, F. J.
- Affiliations
- Universidade do Porto (PT)
- University of Twente (NL)
- Corresponding author
- Ribeiro, Nilza
- Venue
- Biofabrication
- Publisher
- IOP Publishing
- Published
- 2014-06-13
- Volume
- 6
- Issue
- 3
- Pages
- 035015
- ISSN
- 1758-5082 (ISSN-L)
- 1758-5090
- OpenAlex
- W2011131604
- Cited by
- 66
- References
- 53
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 6 · 2023: 6 · 2022: 9 · 2021: 3 · 2020: 1 · 2019: 6 · 2018: 2 · 2017: 12 · 2016: 5 · 2015: 9
- FWCI
- 4.50
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Biofabrication (publishedVersion)
- PubMed (publishedVersion)
- Research Publications (Maastricht University) (publishedVersion, other-oa)
- University of Twente Research Information (publishedVersion)
- Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) (submittedVersion, other-oa)
- Research Publications (Maastricht University) (submittedVersion, other-oa)
- University of Twente Research Information (submittedVersion)
- Funders
- Fundação para a Ciência e a Tecnologia (COMPETE, PEst-C/SAU/LA0002/2013, SFRH/BD/69686/2010)
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › Bone Tissue Engineering Materials
- Physical Sciences › Materials Science › Biomaterials › Electrospun Nanofibers in Biomedical Applications
- Physical Sciences › Materials Science › Biomaterials › Collagen: Extraction and Characterization
- Keywords
- collagen nanofibers, hydroxyapatite nanoparticles, biocomposites, bone regeneration, type I collagen, electrospinning, electrospraying, MC3T3-E1 cells, osteoblast adhesion, elastic modulus, guided bone regeneration, bone defects
- MeSH terms
- Animals, Biocompatible Materials, Bone Regeneration, Collagen, Osteoblasts, Polymers, 3T3 Cells, Durapatite, Tissue Engineering, Cell Proliferation, Mice, Tissue Scaffolds, Electrochemical Techniques, Nanofibers
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