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Engineering a multifunctional 3D-printed PLA-collagen-minocycline-nanoHydroxyapatite scaffold with combined antimicrobial and osteogenic effects for bone regeneration
Abstract
3D-printing and additive manufacturing can be powerful techniques to design customized structures and produce synthetic bone grafts with multifunctional effects suitable for bone repair. In our work we aimed the development of novel multifunctionalized 3D printed poly(lactic acid) (PLA) scaffolds with bioinspired surface coatings able to reduce bacterial biofilm formation while favoring human bone marrow-derived mesenchymal stem cells (hMSCs) activity. For that purpose, 3D printing was used to prepare PLA scaffolds that were further multifunctionalized with collagen (Col), minocycline (MH) and bioinspired citrate- hydroxyapatite nanoparticles (cHA). PLA-Col-MH-cHA scaffolds provide a closer structural support approximation to native bone architecture with uniform macroporous, adequate wettability and an excellent compressive strength. The addition of MH resulted in an adequate antibiotic release profile that by being compatible with local drug delivery therapy was translated into antibacterial activities against Staphylococcus aureus, a main pathogen associated to bone-related infections. Subsequently, the hMSCs response to these scaffolds revealed that the incorporation of cHA significantly stimulated the adhesion, proliferation and osteogenesis-related gene expression (RUNX2, OCN and OPN) of hMSCs. Furthermore, the association of a bioinspired material (cHA) with the antibiotic MH resulted in a combined effect of an enhanced osteogenic activity. These findings, together with the antibiofilm activity depicted strengthen the appropriateness of this 3D-printed PLA-Col-MH-cHA scaffold for future use in bone repair. By targeting bone repair while mitigating the typical infections associated to bone implants, our 3D scaffolds deliver an integrated strategy with the combined effects further envisaging an increase in the success rate of bone-implanted devices.
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“Bioactive compound along with nano-HA/collagen enhanced the osteogenic properties and mechanical property.[107]”
From Nano-hydroxyapatite/collagen composite as scaffold material for bone regeneration. (2023) · cites this paper as [107]
Citations
Cites
Porosity of 3D biomaterial scaffolds and osteogenesis
Karageorgiou, V., & Kaplan, D. L. (2005) · Biomaterials · doi:10.1016/j.biomaterials.2005.02.002 · Cited by 6,639
Farah, S., Anderson, D. G., & Langer, R. (2016) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2016.06.012 · Cited by 3,443
3D printing with polymers: Challenges among expanding options and opportunities
Stansbury, J. W., & Idacavage, M. J. (2015) · Dental Materials · doi:10.1016/j.dental.2015.09.018 · Cited by 1,758
Lebeaux, D., Ghigo, J., & Beloin, C. (2014) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.00013-14 · Cited by 1,378
The significance of infection related to orthopedic devices and issues of antibiotic resistance
Campoccia, D., Montanaro, L., & Arciola, C. R. (2005) · Biomaterials · doi:10.1016/j.biomaterials.2005.11.044 · Cited by 1,113
3D Printing of Scaffolds for Tissue Regeneration Applications
Do, A., Khorsand, B., Geary, S. M., & Salem, A. K. (2015) · Advanced Healthcare Materials · doi:10.1002/adhm.201500168 · Cited by 949
Minocycline: Far beyond an Antibiotic
Garrido‐Mesa, N., Zarzuelo, A., & Gálvez, J. (2013) · British Journal of Pharmacology · doi:10.1111/bph.12139 · Cited by 935
Bone biomaterials and interactions with stem cells
Gao, C., Peng, S., Feng, P., & Shuai, C. (2017) · Bone Research · doi:10.1038/boneres.2017.59 · Cited by 748
How microorganisms use hydrophobicity and what does this mean for human needs?
Krasowska, A., & Sigler, K. (2014) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2014.00112 · Cited by 670
New insights into the biology of osteocalcin
Zoch, M. L., Clemens, T. L., & Riddle, R. C. (2015) · Bone · doi:10.1016/j.bone.2015.05.046 · Cited by 612
Mimicking biological functionality with polymers for biomedical applications
Green, J. J., & Elisseeff, J. H. (2016) · Nature · doi:10.1038/nature21005 · Cited by 501
Osteoblast Differentiation and Bone Matrix Formation In Vivo and In Vitro
Blair, H. C., Larrouture, Q. C., Li, Y., Lin, H., Beer-Stoltz, D., Liu, L., Tuan, R. S., Robinson, L. J., Schlesinger, P. H., & Nelson, D. J. (2016) · Tissue Engineering Part B Reviews · doi:10.1089/ten.teb.2016.0454 · Cited by 486
Calcium/calmodulin signaling controls osteoblast growth and differentiation
Zayzafoon, M. (2005) · Journal of Cellular Biochemistry · doi:10.1002/jcb.20675 · Cited by 438
Designing of PLA scaffolds for bone tissue replacement fabricated by ordinary commercial 3D printer
Gregor, A., Filová, E., Novák, M., Kronek, J., Chlup, H., Buzgo, M., Blahnová, V. H., Lukášová, V., Bartoš, M., Nečas, A., et al. (2017) · Journal of Biological Engineering · doi:10.1186/s13036-017-0074-3 · Cited by 407
Nanotechnology in bone tissue engineering
Walmsley, G. G., McArdle, A., Tevlin, R., Momeni, A., Atashroo, D. A., Hu, M. S.-M., Feroze, A. H., Wong, V., Lorenz, H. P., Longaker, M. T., et al. (2015) · Nanomedicine Nanotechnology Biology and Medicine · doi:10.1016/j.nano.2015.02.013 · Cited by 294
Recent advances in nano scaffolds for bone repair
Yi, H., Rehman, F. U., Zhao, C., Liu, B., & He, N. (2016) · Bone Research · doi:10.1038/boneres.2016.50 · Cited by 267
Chitosan Nanoparticles as a Mucoadhesive Drug Delivery System for Ocular Administration
da Silva, M. D. F. R., Calado, R., Marto, J. M., Bettencourt, A., Almeida, A. J., & Gonçalves, L. (2017) · Marine Drugs · doi:10.3390/md15120370 · Cited by 263
Self-citationCollagen–hyaluronic acid scaffolds for adipose tissue engineering
Davidenko, N., Campbell, J. J., Thian, E. S., Watson, C. J., & Cameron, R. E. (2010) · Acta Biomaterialia · doi:10.1016/j.actbio.2010.05.005 · Cited by 259
Minocycline Up-regulates Bcl-2 and Protects against Cell Death in Mitochondria
Wang, J., Wei, Q., Wang, C., Hill, W., Hess, D. C., & Dong, Z. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m313629200 · Cited by 242
The nanocomposite nature of bone drives its strength and damage resistance
Tertuliano, O. A., & Greer, J. R. (2016) · Nature Materials · doi:10.1038/nmat4719 · Cited by 227
Barba, A., Díez-Escudero, A., Maazouz, Y., Rappe, K., Español, M., Montúfar, E. B., Bonany, M., Sadowska, J. M., Guillem‐Marti, J., Öhman‐Mägi, C., et al. (2017) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.7b14175 · Cited by 224
Wang, M., Favi, P. M., Cheng, X., Golshan, N. H., Ziemer, K. S., Keidar, M., & Webster, T. J. (2016) · Acta Biomaterialia · doi:10.1016/j.actbio.2016.09.030 · Cited by 219
Zhang, W., Feng, C., Yang, G., Li, G., Ding, X., Wang, S., Yuandong, D., Zhang, Z., Chang, J., Wu, C., et al. (2017) · Biomaterials · doi:10.1016/j.biomaterials.2017.05.005 · Cited by 219
Lu, Y., Li, L., Zhu, Y., Wang, X., Li, M., Lin, Z., Hu, X., Zhang, Y., Yin, Q., Xia, H., et al. (2017) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.7b13750 · Cited by 188
Bone regeneration: Biomaterials as local delivery systems with improved osteoinductive properties
Martín, V., & Bettencourt, A. (2017) · Materials Science and Engineering C · doi:10.1016/j.msec.2017.04.038 · Cited by 169
Self-citationNanoengineered biomaterials for repair and regeneration of orthopedic tissue interfaces
Cross, L., Thakur, A., Jalili, N. A., Detamore, M. S., & Gaharwar, A. K. (2016) · Acta Biomaterialia · doi:10.1016/j.actbio.2016.06.023 · Cited by 141
Viti, F., Landini, M., Mezzelani, A., Petecchia, L., Milanesi, L., & Scaglione, S. (2016) · PLoS ONE · doi:10.1371/journal.pone.0148173 · Cited by 138
Roh, H.-S., Lee, C.-M., Hwang, Y.-H., Kook, M.-S., Yang, S.-W., Lee, D., & Kim, B. (2016) · Materials Science and Engineering C · doi:10.1016/j.msec.2016.12.054 · Cited by 117
Stimulation of 3D osteogenesis by mesenchymal stem cells using a nanovibrational bioreactor
Tsimbouri, P. M., Childs, P. G., Pemberton, G. D., Yang, J., Jayawarna, V., Orapiriyakul, W., Burgess, K., González‐García, C., Blackburn, G. J., Thomas, D., et al. (2017) · Nature Biomedical Engineering · doi:10.1038/s41551-017-0127-4 · Cited by 114
Visscher, L. E., Dang, H. P., Knackstedt, M. A., Hutmacher, D. W., & Tran, P. A. (2018) · Materials Science and Engineering C · doi:10.1016/j.msec.2018.02.008 · Cited by 113
Gomes, P. S., & Fernandes, M. H. (2006) · Archives of Oral Biology · doi:10.1016/j.archoralbio.2006.10.005 · Cited by 106
Self-citationEffect of xylitol, sodium fluoride and triclosan containing mouth rinse on Streptococcus mutans
Subramaniam, P., & Nandan, N. (2011) · Contemporary Clinical Dentistry · doi:10.4103/0976-237x.91790 · Cited by 99
Bakhshandeh, S., Karaji, Z. G., Lietaert, K., Fluit, A. C., Boel, C. H. E., Vogely, H. C., Vermonden, T., Hennink, W. E., Weinans, H., ZADPOOR, A. A., et al. (2017) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.7b04950 · Cited by 98
Bala, Y., & Seeman, E. (2015) · Calcified Tissue International · doi:10.1007/s00223-015-9971-y · Cited by 94
Can Sophorolipids prevent biofilm formation on silicone catheter tubes?
Pontes, C. M., Alves, M. M., Santos, C. F., Ribeiro, M. H. L., Gonçalves, L., Bettencourt, A., & Ribeiro, I. (2016) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2016.09.074 · Cited by 92
Self-citationKargozar, S., Hashemian, S. J., Soleimani, M., Milan, P. B., Askari, M., Khalaj, V., Samadikuchaksaraei, A., Hamzehlou, S., Katebi, A. R., Latifi, N., et al. (2017) · Materials Science and Engineering C · doi:10.1016/j.msec.2017.02.097 · Cited by 87
In vitro characterization of 3D printed scaffolds aimed at bone tissue regeneration
Boga, J. C., Miguel, S. P., de Melo‐Diogo, D., Mendonça, A., Louro, R. O., & Correia, I. J. (2018) · Colloids and Surfaces B Biointerfaces · doi:10.1016/j.colsurfb.2018.02.038 · Cited by 84
Joly, P., Duda, G. N., Schöne, M., Welzel, P. B., Freudenberg, U., Werner, C., & Petersen, A. (2013) · PLoS ONE · doi:10.1371/journal.pone.0073545 · Cited by 82
Control of Nanoparticle Release Kinetics from 3D Printed Hydrogel Scaffolds
Baumann, B., Jüngst, T., Stichler, S., Feineis, S., Wiltschka, O., Kuhlmann, M., Lindén, M., & Gröll, J. (2017) · Angewandte Chemie International Edition · doi:10.1002/anie.201700153 · Cited by 74
Ritz, U., Gerke, R., Götz, H., Stein, S., & Rommens, P. M. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18122569 · Cited by 72
Carvalho, Â., Cangueiro, L., Oliveira, V., Vilar, R., Fernandes, M. H., & Monteiro, F. J. (2017) · Applied Surface Science · doi:10.1016/j.apsusc.2017.11.206 · Cited by 64
Self-citationLarrañaga, A., Aldazábal, P., Martín, F., & Sarasua, J.-R. (2014) · Polymer Degradation and Stability · doi:10.1016/j.polymdegradstab.2014.08.021 · Cited by 62
Tilakaratne, A., & Soory, M. (2014) · The Open Dentistry Journal · doi:10.2174/1874210601408010109 · Cited by 59
Cell-induced response by tetracyclines on human bone marrow colonized hydroxyapatite and Bonelike®
Gomes, P. S., Santos, J. D., & Fernandes, M. H. (2008) · Acta Biomaterialia · doi:10.1016/j.actbio.2007.12.006 · Cited by 57
Self-citationMarques, C. F., Olhero, S. M., Torres, P. M. C., Abrantes, J. C. C., Fateixa, S., Nogueira, H. I. S., Ribeiro, I., Bettencourt, A., Sousa, A., Granja, P. L., et al. (2018) · Materials Science and Engineering C · doi:10.1016/j.msec.2018.09.050 · Cited by 56
Self-citationQuan, H., He, Y., Sun, J., Yang, W., Luo, W., Dou, C., Kang, F., Zhao, C., He, J., Yang, X., et al. (2018) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.8b09879 · Cited by 55
Three-Dimensional Printing of Carbamazepine Sustained-Release Scaffold
Lim, S. H., Chia, S. M. Y., Kang, L., & Yap, K. Y. (2016) · Journal of Pharmaceutical Sciences · doi:10.1016/j.xphs.2016.04.031 · Cited by 54
Ferreira, M., Rzhepishevska, O. I., Grenho, L., Malheiros, D., Gonçalves, L., Almeida, A. J., Jordão, L., Ribeiro, I., Ramstedt, M., Gomes, P. S., et al. (2017) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2017.08.089 · Cited by 48
Self-citationSantos, C. F., Gomes, P. S., Duarte, J. A., Franke, R.-P., Almeida, M. M., Costa, M. E. V., & Fernandes, M. H. (2012) · Journal of The Royal Society Interface · doi:10.1098/rsif.2012.0487 · Cited by 48
Self-citationKim, S. E., Yun, Y.-P., Shim, K.-S., Kim, H. J., Park, K., & Song, H. (2016) · Biomedical Materials · doi:10.1088/1748-6041/11/5/055005 · Cited by 48
Surface modification of poly (lactic acid) with an improved alkali-acid hydrolysis method
Guo, C., Xiang, M., & Dong, Y. (2014) · Materials Letters · doi:10.1016/j.matlet.2014.10.099 · Cited by 46
Kim, J. I., & Kim, C. S. (2018) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.7b19182 · Cited by 33
Matos, A. C., Ribeiro, I., Guedes, R. C., Pinto, R. V., Vaz, M. A. P., Gonçalves, L., Almeida, A. J., & Bettencourt, A. (2015) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2015.03.035 · Cited by 32
Self-citationShen, Y., Ma, Y., Gao, M., Lai, Y., Wang, G., Yu, Q., Cui, F., & Liu, X. (2013) · ACS Applied Materials & Interfaces · doi:10.1021/am400973a · Cited by 30
Protective Effect of Minocycline Against Cisplatin-induced Ototoxicity
Lee, C.-K., Shin, J., & Cho, Y. (2011) · Clinical and Experimental Otorhinolaryngology · doi:10.3342/ceo.2011.4.2.77 · Cited by 26
Marycz, K., Pązik, R., Zawisza, K., Wiglusz, K., Marędziak, M., Sobierajska, P., & Wiglusz, R. J. (2016) · Materials Science and Engineering C · doi:10.1016/j.msec.2016.06.051 · Cited by 23
Surface characterization and osteoblast-like Cells culture on collagen modified PLDLA scaffolds
Más, B. A., Cattani, S. M. M., Rangel, R. D. C. C., Ribeiro, G. D. A., da Cruz, N. C., Leite, F. L., Nascente, P. A. P., & Duek, E. A. D. R. (2014) · Materials Research · doi:10.1590/1516-1439.269414 · Cited by 22
Silva, T., Grenho, L., Barros, J., Silva, J. C., Pinto, R. V., Matos, A. C., Colaço, B., Fernandes, M. H., Bettencourt, A., & Gomes, P. S. (2017) · Biomedical Materials · doi:10.1088/1748-605x/aa68b8 · Cited by 16
Self-citationCosta‐Rodrigues, J., Silva, A., Santos, C. F., Almeida, M. M., Costa, M. E. V., & Fernandes, M. H. (2014) · Journal of Biomedical Nanotechnology · doi:10.1166/jbn.2014.1873 · Cited by 14
Self-citation
Flagged first, then by citations
Research works printed but not linked: 6
- Sung Eun, 2016, Biomed. Mater., 11
- Bae, 2018, Biomed. Res. Int., 12
- Tiago, 2017, Biomed. Mater., 12
- Oliveira, 2013, Adv. Mater. Sci. Eng., 14
- Xiao-Chen, 2011, Biomed. Mater., 6
- Dong, 2018, J. Biomed. Mater. Res. A, 1
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Current applications of poly(lactic acid) composites in tissue engineering and drug delivery
Liu, S., Qin, S., He, M., Zhou, D., Qin, Q., & Wang, H. (2020) · Composites Part B: Engineering · doi:10.1016/j.compositesb.2020.108238 · Cited by 533
Zhu, G., Zhang, T., Chen, M., Yao, K., Huang, X., Zhang, B., Li, Y., Liu, J., Wang, Y., & Zhao, Z. (2021) · Bioactive Materials · doi:10.1016/j.bioactmat.2021.03.043 · Cited by 516
Multifunctional antimicrobial materials: From rational design to biomedical applications
Duan, S., Wu, R., Xiong, Y., Ren, H., Lei, C., Zhao, Y., Zhang, X., & Xu, F. (2021) · Progress in Materials Science · doi:10.1016/j.pmatsci.2021.100887 · Cited by 260
Biomaterials and nanomedicine for bone regeneration: Progress and future prospects
Zhou, J. M., Zhang, Z., Joseph, J., Zhang, X., Ferdows, B. E., Patel, D. N., Chen, W., Banfi, G., Molinaro, R., Cosco, D., et al. (2021) · Exploration · doi:10.1002/exp.20210011 · Cited by 254
Metadata
- Authors
- Martin, V., Ribeiro, I. A., Alves, M. M., Gonçalves, L., Claudio, R. A., Grenho, L., Fernandes, M. H., Gomes, P., Santos, C. F., & Bettencourt, A. F.
- Affiliations
- University of Lisbon (PT)
- Universidade do Porto (PT)
- Corresponding author
- Santos, Catarina F.
- Bettencourt, Ana F.
- ORCID
- Venue
- Materials Science and Engineering: C
- Publisher
- Elsevier BV
- Published
- 2019-08
- Volume
- 101
- Pages
- 15-26
- ISSN
- 0928-4931 (ISSN-L)
- OpenAlex
- W2923561240
- Cited by
- 181
- References
- 59
- Citations by year
- 2026: 8 · 2025: 16 · 2024: 32 · 2023: 25 · 2022: 26 · 2021: 39 · 2020: 30 · 2019: 4
- FWCI
- 8.71
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Materials Science and Engineering C (publishedVersion)
- PubMed (publishedVersion)
- Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) (submittedVersion)
- Funders
- Fundação para a Ciência e a Tecnologia (SFRH/BPD/76646/2011, UID/QUI/00100/2013, PT2020 UID/QUI/50006/2013, UID/DTP/04138/2014)
- Ministério da Educação e Ciência
- European Commission (POCI/01/0145/FEDER/007265)
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › Bone Tissue Engineering Materials
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Physical Sciences › Engineering › Industrial and Manufacturing Engineering › Additive Manufacturing and 3D Printing Technologies
- Keywords
- 3D-printed scaffolds, polylactic acid, collagen, minocycline, bone regeneration, bone grafting, osteogenic differentiation, mesenchymal stem cells, antibacterial activity, biofilm inhibition, Staphylococcus aureus, antibiotic release, local drug delivery
- MeSH terms
- Adsorption, Anti-Bacterial Agents, Bone Regeneration, Collagen, Gene Expression Regulation, Humans, Microbial Sensitivity Tests, Minocycline, Osteogenesis, Polyesters, Staphylococcus aureus, Osseointegration, Durapatite, Biofilms, Tissue Engineering, Nanoparticles, Tissue Scaffolds, Mesenchymal Stem Cells, Drug Liberation, Printing, Three-Dimensional
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