Gelatin/Hyaluronic Acid Photocrosslinked Double Network Hydrogel with Nano-Hydroxyapatite Composite for Potential Application in Bone Repair
Abstract
:1. Introduction
2. Results and Discussion
2.1. Preparation of GelMA/HAMA/nHap Composite Hydrogels
2.2. Characterization of GelMA/HAMA/nHap Composite Hydrogels
2.3. Compressive Strength of GelMA/HAMA/nHap Composite Hydrogels
2.4. The Swelling Ratio of GelMA/HAMA/nHap Composite Hydrogels
2.5. In Vitro Cytocompatibility of GelMA/HAMA/nHap Composite Hydrogels
3. Conclusions
4. Materials and Methods
4.1. Materials
4.2. Preparation of GelMA/HAMA/nHap Composite Hydrogels
4.2.1. Preparation of the Precursor Solutions of the Hydrogels
4.2.2. Rheological Testing of the Precursor Solutions of the Hydrogels
4.2.3. Preparation of the Hydrogels
4.3. Characterization of GelMA/HAMA/nHap Composite Hydrogels
4.4. Compressive Strength Testing
4.5. Evaluation of the Swelling Ratio
4.6. In Vitro Cytocompatibility Studies
4.6.1. Effects of the Composite Hydrogels on Proliferation Behavior of BMSCs
4.6.2. Effects of the Composite Hydrogels on the Viability of BMSCs
4.7. Statistical Analysis
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Turnbull, G.; Clarke, J.; Picard, F.; Riches, P.; Jia, L.; Han, F.; Li, B.; Shu, W. 3D bioactive composite scaffolds for bone tissue engineering. Bioact. Mater. 2018, 3, 278–314. [Google Scholar] [CrossRef]
- Montoya, C.; Du, Y.; Gianforcaro, A.L.; Orrego, S.; Yang, M.; Lelkes, P.I. On the road to smart biomaterials for bone research: Definitions, concepts, advances, and outlook. Bone Res. 2021, 9, 12. [Google Scholar] [CrossRef]
- Armiento, A.R.; Hatt, L.P.; Rosenberg, G.S.; Thompson, K.; Stoddart, M.J. Functional biomaterials for bone regeneration: A lesson in complex biology. Adv. Funct. Mater. 2020, 30, 1909874. [Google Scholar] [CrossRef]
- Collins, M.N.; Ren, G.; Young, K.; Pina, S.; Reis, R.L.; Oliveira, J.M. Scaffold fabrication technologies and structure/function properties in bone tissue engineering. Adv. Funct. Mater. 2021, 31, 2010609. [Google Scholar] [CrossRef]
- Xie, C.; Ye, J.; Liang, R.; Yao, X.; Wu, X.; Koh, Y.; Wei, W.; Zhang, X.; Ouyang, H. Advanced strategies of biomimetic tissue-engineered grafts for bone regeneration. Adv. Healthc. Mater. 2021, 10, 2100408. [Google Scholar] [CrossRef] [PubMed]
- Vermeulen, S.; Birgani, Z.T.; Habibovic, P. Biomaterial-induced pathway modulation for bone regeneration. Biomaterials 2022, 283, 121431. [Google Scholar] [CrossRef]
- Ho, A.S. Hydrogels for biomedical applications. Adv. Drug Deliv. Rev. 2012, 64, 18–23. [Google Scholar]
- Drury, J.L.; Mooney, D.J. Hydrogels for tissue engineering: Scaffold design variables and applications. Biomaterials 2003, 24, 4337–4351. [Google Scholar] [CrossRef]
- Xue, X.; Hu, Y.; Deng, Y.; Su, J. Recent advances in design of functional biocompatible hydrogels for bone tissue engineering. Adv. Funct. Mater. 2021, 31, 2009432. [Google Scholar] [CrossRef]
- Aldana, A.A.; Houben, S.; Moroni, L.; Baker, M.B.; Pitet, L.M. Trends in double networks as bioprintable and injectable hydrogel scaffolds for tissue regeneration. ACS Biomater. Sci. Eng. 2021, 7, 4077–4101. [Google Scholar] [CrossRef]
- Dragan, E.S. Design and applications of interpenetrating polymer network hydrogels. a review. Chem. Eng. J. 2014, 243, 572–590. [Google Scholar] [CrossRef]
- Ren, Y.; Zhang, Y.; Zhang, H.; Wang, Y.; Liu, L.; Zhang, Q. A Gelatin-hyaluronic acid double cross-linked hydrogel for regulating the growth and dual dimensional cartilage differentiation of bone marrow mesenchymal stem cells. J. Biomed. Nanotechnol. 2021, 17, 1044–1057. [Google Scholar] [CrossRef]
- Wang, Y.; Chen, Y.; Zheng, J.; Liu, L.; Zhang, Q. Three-dimensional printing self-healing dynamic/photocrosslinking gelatin-hyaluronic acid double-network hydrogel for tissue engineering. ACS Omega 2022, 7, 12076–12088. [Google Scholar] [CrossRef]
- Zhang, H.; Huang, H.; Hao, G.; Zhang, Y.; Ding, H.; Fan, Z.; Sun, L. 3D Printing hydrogel scaffolds with nanohydroxyapatite gradient to effectively repair osteochondral defects in rats. Adv. Funct. Mater. 2021, 31, 2006697. [Google Scholar] [CrossRef]
- Pina, S.; Oliveira, J.M.; Reis, R.L. Natural-based Nanocomposites for bone tissue engineering and regenerative medicine: A review. Adv. Mater. 2015, 27, 1143–1169. [Google Scholar] [CrossRef]
- Wu, X.; Zhang, T.; Ho, B.; Suvarnapathaki, S.; Lantigua, D.; McCarthy, C.; Wu, B.; Camci-Unal, G. Mineralized hydrogels induce bone regeneration in critical size cranial defects. Adv. Healthc. Mater. 2021, 10, 2001101. [Google Scholar] [CrossRef] [PubMed]
- Heid, S.; Boccaccini, A.R. Advancing bioinks for 3D bioprinting using reactive fillers: A review. Acta Biomater. 2020, 113, 1–22. [Google Scholar] [CrossRef] [PubMed]
- Naleway, S.E.; Porter, M.M.; McKittrick, J.; Meyers, M.A. Structural design elements in biological materials: Application to bioinspiration. Adv. Mater. 2015, 27, 5455–5476. [Google Scholar] [CrossRef] [PubMed]
- Asim, S.; Tabish, T.A.; Liaqat, U.; Ozbolat, I.T.; Rizwan, M. Advances in gelatin bioinks to optimize bioprinted cell functions. Adv. Healthc. Mater. 2023, 12, 2203148. [Google Scholar] [CrossRef]
- Kurian, A.G.; Singh, R.K.; Patel, K.D.; Lee, J.-H.; Kim, H.-W. Multifunctional GelMA platforms with nanomaterials for advanced tissue therapeutics. Bioact. Mater. 2022, 8, 267–295. [Google Scholar] [CrossRef]
- Zhai, P.; Peng, X.; Li, B.; Liu, Y.; Sun, H.; Li, X. The application of hyaluronic acid in bone regeneration. Int. J. Biol. Macromol. 2020, 151, 1224–1239. [Google Scholar] [CrossRef]
- Grieco, M.; Ursini, O.; Palama, I.E.; Gigli, G.; Moroni, L.; Cortese, B. HYDRHA: Hydrogels of hyaluronic acid. New biomedical approaches in cancer, neurodegenerative diseases, and tissue engineering. Mater. Today Bio 2022, 17, 100453. [Google Scholar] [CrossRef] [PubMed]
- Van Den Bulcke, A.I.; Bogdanov, B.; De Rooze, N.; Schacht, E.H.; Cornelissen, M.; Berghmans, H. Structural and rheological properties of methacrylamide modiffed gelatin hydrogels. Biomacromolecules 2000, 1, 31–38. [Google Scholar] [CrossRef] [PubMed]
- Yue, K.; Satiage, G.T.-D.; Alvarez, M.M.; Tamayol, A.; Annabi, N.; Khademhosseini, A. Synthesis, properties, and biomedical applications of gelatin methacryloyl (GelMA) hydrogels. Biomaterials 2015, 73, 254–271. [Google Scholar] [CrossRef]
- Chimene, D.; Kaunas, R.; Gaharwar, A.K. Hydrogel bioink reinforcement for additive manufacturing: A focused review of emerging strategies. Adv. Mater. 2020, 32, 1902026. [Google Scholar] [CrossRef]
- Tong, L.; Pu, X.; Liu, Q.; Li, X.; Chen, M.; Wang, P.; Zou, Y.; Lu, G.; Liang, J.; Fan, Y.; et al. Nanostructured 3D-printed hybrid scaffold accelerates bone regeneration by photointegrating nanohydroxyapatite. Adv. Sci. 2023, 10, 2300038. [Google Scholar] [CrossRef] [PubMed]
- Gregory, T.; Benhal, P.; Scutte, A.; Quashie, D., Jr.; Harrison, K.; Cargill, C.; Grandison, S.; Savitsky, M.J.; Ramakrishnan, S.; Ali, J. Rheological characterization of cell-laden alginate-gelatin hydrogels for 3D biofabrication. J. Mech. Behav. Biomed. Mater. 2022, 136, 105474. [Google Scholar] [CrossRef]
- Li, Y.; Xiao, L.; Wei, D.; Liu, S.; Zhang, Z.; Lian, R.; Wang, L.; Chen, Y.; Jiang, J.; Xiao, Y.; et al. Injectable biomimetic hydrogel guided functional bone regeneration by adapting material degradation to tissue healing. Adv. Funct. Mater. 2023, 33, 2213047. [Google Scholar] [CrossRef]
- Wilson, S.A.; Cross, L.M.; Peak, C.W.; Gaharwar, A.K. Shear-thinning and thermo-reversible nanoengineered inks for 3D bioprinting. ACS Appl. Mater. Interfaces 2017, 9, 43449–43458. [Google Scholar] [CrossRef]
- Hou, M.; Wang, X.; Yue, O.; Zheng, M.; Zhang, H.; Liu, X. Development of a multifunctional injectable temperature-sensitive gelatin-based adhesive double-network hydrogel. Biomater. Adv. 2022, 134, 112556. [Google Scholar] [CrossRef]
- Ouyang, L.; Highley, C.B.; Rodell, C.B.; Sun, W.; Burdick, J.A. 3D printing of shear-thinning hyaluronic acid hydrogels with secondary cross-Linking. ACS Biomater. Sci. Eng. 2016, 2, 1743–1751. [Google Scholar] [CrossRef] [PubMed]
- Liu, L.; Zhang, L.; Ren, B.; Wang, F. Preparation and characterization of collagen-hydroxyapatite composite used for bone tissue engineering scaffold. Artif. Cell Blood Sub. 2003, 31, 435–448. [Google Scholar] [CrossRef] [PubMed]
- Tang, S.; Dong, Z.; Ke, X.; Luo, J.; Li, J. Advances in biomineralization-inspired materials for hard tissue repair. Int. J. Oral Sci. 2021, 13, 42. [Google Scholar] [CrossRef]
- Ren, Y.; Zhang, H.; Qin, W.; Du, B.; Liu, L.; Yang, J. A collagen mimetic peptide-modified hyaluronic acid hydrogel system with enzymatically mediated degradation for mesenchymal stem cell differentiation. Mat. Sci. Eng. C-Mater. 2020, 108, 110276. [Google Scholar] [CrossRef] [PubMed]
- Jabbari, E. Hydrogels for cell delivery. Gels 2018, 4, 58. [Google Scholar] [CrossRef]
- Ren, Y.; Zhang, H.; Wang, Y.; Du, B.; Yang, J.; Liu, L.; Zhang, Q. Hyaluronic Acid Hydrogel with Adjustable Stiffness for Mesenchymal Stem Cell 3D Culture via Related Molecular Mechanisms to Maintain Stemness and Induce Cartilage Differentiation. ACS Appl. Bio Mater. 2021, 4, 2601–2613. [Google Scholar] [CrossRef]
- Wu, D.T.; Jeffreys, N.; Diba, M.; Mooney, D.J. Viscoelastic Biomaterials for Tissue Regeneration. Tissue Eng. Part C-Methods 2022, 28, 289–300. [Google Scholar] [CrossRef]
- Bertsch, P.; Diba, M.; Mooney, D.J.; Leeuwenburgh, S.C.G. Self-healing injectable hydrogels for tissue regeneration. Chem. Rev. 2023, 123, 834–873. [Google Scholar] [CrossRef]
Sample | C (%) | O (%) | N (%) | Ca (%) | P (%) |
---|---|---|---|---|---|
10%GelMA/2%HAMA | 64.33 | 23.55 | 10.83 | 0.14 | 1.16 |
10%GelMA/2%HAMA/0.5%nHap | 68.02 | 22.42 | 8.96 | 0.26 | 0.35 |
10%GelMA/2%HAMA/1%nHap | 61.11 | 25.38 | 11.93 | 0.67 | 0.92 |
Hydrogel Formulations | Notations |
---|---|
2%HAMA, 98%PBS | 2%HAMA |
10%GelMA, 90%PBS | 10%GelMA |
10%GelMA, 2%HAMA, 88%PBS | 10%GelMA/2%HAMA |
10%GelMA, 2%HAMA, 0.5%nHap, 87.5%PBS | 10%GelMA/2%HAMA/0.5%nHap |
10%GelMA, 2%HAMA, 1%nHap, 87%PBS | 10%GelMA/2%HAMA/1%nHap |
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Zheng, J.; Wang, Y.; Wang, Y.; Duan, R.; Liu, L. Gelatin/Hyaluronic Acid Photocrosslinked Double Network Hydrogel with Nano-Hydroxyapatite Composite for Potential Application in Bone Repair. Gels 2023, 9, 742. https://doi.org/10.3390/gels9090742
Zheng J, Wang Y, Wang Y, Duan R, Liu L. Gelatin/Hyaluronic Acid Photocrosslinked Double Network Hydrogel with Nano-Hydroxyapatite Composite for Potential Application in Bone Repair. Gels. 2023; 9(9):742. https://doi.org/10.3390/gels9090742
Chicago/Turabian StyleZheng, Jianuo, Yunping Wang, Yuwen Wang, Ruiping Duan, and Lingrong Liu. 2023. "Gelatin/Hyaluronic Acid Photocrosslinked Double Network Hydrogel with Nano-Hydroxyapatite Composite for Potential Application in Bone Repair" Gels 9, no. 9: 742. https://doi.org/10.3390/gels9090742