Hybrid hydrogels for bioink development and potential use in dental tissue engineering


  • Teodora Prebeg Department of Mechanical and Thermal Process Engineering, Faculty of Chemical Engineering and Technology, University of Zagreb, 10000 Zagreb, Croatia https://orcid.org/0000-0001-6235-278X
  • Željka Perić Kačarević Department of Anatomy Histology, Embryology, Pathology Anatomy and Pathology Histology, Faculty of Dental Medicine and Health, University of Osijek, 31000 Osijek, Croatia https://orcid.org/0000-0002-8250-723X
  • Gordana Matijašić Department of Mechanical and Thermal Process Engineering, Faculty of Chemical Engineering and Technology, University of Zagreb, 10000 Zagreb, Croatia https://orcid.org/0000-0002-8521-2154




hybrid hydrogel, bioink, tissue engineering


One of the emerging problems in medicine and dentistry today is how to replace and regenerate damaged tissue. Currently used implants are inert and need to be replaced after a certain period. Therefore, the aim is to develop a bioactive multicomponent material that can promote tissue regeneration. Hydrogels are the focus of research in this field because of their similarity to the natural extracellular matrix and their good biocompatibility. Nevertheless, hydrogels often have insufficient mechanical properties for handling and implantation. Therefore, methods of hydrogel reinforcement are developed by adding at least one phase to obtain hybrid hydrogels. There are various methods to reinforce hydrogels, such as functionalization, interpenetrating networks, nanogels, nano-engineered ionic covalent entanglement, etc. The obtained hybrid hydrogel can be used to develop a bioink, a biocompatible and biodegradable material mixed with cells that has suitable properties for 3D bioprinting. The 3D bioprinting method is used to obtain scaffolds of the desired shape and size. Hybrid hydrogel-based 3D printed scaffolds have shown great potential in biological assessment to promote the regeneration of a variety of tissues.


S. Ostrovidov et al., “Bioprinting and biomaterials for dental alveolar tissue regeneration,” Front. Bioeng. Biotechnol., vol. 11, no. April, pp. 1–14, 2023, doi: 10.3389/fbioe.2023.991821.

Y. S. Kim, M. Majid, A. J. Melchiorri, and A. G. Mikos, “Applications of decellularized extracellular matrix in bone and cartilage tissue engineering,” Bioeng. Transl. Med., vol. 4, no. 1, pp. 83–95, 2019, doi: 10.1002/btm2.10110.

T. Lu, Y. Li, and T. Chen, “Techniques for fabrication and construction of three-dimensional scaffolds for tissue engineering,” Int. J. Nanomedicine, vol. 8, pp. 337–350, 2013, doi: 10.2147/IJN.S38635.

N. Mohd, M. Razali, M. B. Fauzi, and N. H. Abu Kasim, “In Vitro and In Vivo Biological Assessments of 3D-Bioprinted Scaffolds for Dental Applications,” Int. J. Mol. Sci., vol. 24, no. 16, pp. 12881–12903, 2023, doi: 10.3390/ijms241612881.

Y. Ma, L. Xie, B. Yang, and W. Tian, “Three-dimensional printing biotechnology for the regeneration of the tooth and tooth-supporting tissues,” Biotechnol. Bioeng., vol. 116, no. 2, pp. 452–468, 2019, doi: 10.1002/bit.26882.

R. Levato, T. Jungst, R. G. Scheuring, T. Blunk, J. Groll, and J. Malda, “From Shape to Function: The Next Step in Bioprinting,” Adv. Mater., vol. 32, no. 12, 2020, doi: 10.1002/adma.201906423.

C. Vasile, D. Pamfil, E. Stoleru, and M. Baican, “New developments in medical applications of hybrid hydrogels containing natural polymers,” Molecules, vol. 25, no. 7, pp. 1539–1607, 2020, doi: 10.3390/molecules25071539.

D. Chimene, R. Kaunas, and A. K. Gaharwar, “Hydrogel Bioink Reinforcement for Additive Manufacturing: A Focused Review of Emerging Strategies,” Adv. Mater., vol. 32, no. 1, pp. 1–22, 2020, doi: 10.1002/adma.201902026.

N. A. Peppas and A. S. Hoffman, “Hydrogels,” Biomater. Sci. An Introd. to Mater. Med., no. 1, pp. 153–166, 2020, doi: 10.1016/B978-0-12-816137-1.00014-3.

D. Chimene, K. K. Lennox, R. R. Kaunas, and A. K. Gaharwar, “Advanced Bioinks for 3D Printing: A Materials Science Perspective,” Ann. Biomed. Eng., vol. 44, no. 6, pp. 2090–2102, 2016, doi: 10.1007/s10439-016-1638-y.

Y. S. Zhang and A. Khademhosseini, “Advances in engineering hydrogels,” Science (80-. )., vol. 356, no. 6337, pp. 139–148, 2017, doi: 10.1126/science.aaf3627.Advances.

J. M. Rosiak and F. Yoshii, “Hydrogels and their medical applications,” Nucl. Instruments Methods Phys. Res. Sect. B Beam Interact. with Mater. Atoms, vol. 151, no. 1–4, pp. 56–64, 1999, doi: 10.1016/S0168-583X(99)00118-4.

L. L. Palmese, R. K. Thapa, M. O. Sullivan, and K. L. Kiick, “Hybrid hydrogels for biomedical applications,” Curr. Opin. Chem. Eng., vol. 24, pp. 143–157, 2019, doi: 10.1016/j.coche.2019.02.010.

P. J. B. Ruben F. Pereira, “3D bioprinting of photocrosslinkable hydrogel constructs,” J. Appl. Polym. Sci., vol. 132, no. 48, pp. 42458–42473, 2015, doi: 10.1002/app.42889.

B. J. Klotz, D. Gawlitta, A. J. W. P. Rosenberg, J. Malda, and P. W. Melchels, “Gelatin-Methacryloyl Hydrogels: Towards Biofabrication-Based Tissue Repair,” vol. 34, no. 5, pp. 394–407, 2018, doi: 10.1016/j.tibtech.2016.01.002.Gelatin-Methacryloyl.

J. W. Nichol, S. T. Koshy, H. Bae, C. M. Hwang, S. Yamanlar, and A. Khademhosseini, “Cell-laden microengineered gelatin methacrylate hydrogels,” Biomaterials, vol. 31, no. 21, pp. 5536–5544, 2010, doi: 10.1016/j.biomaterials.2010.03.064.

S. Bertlein et al., “Thiol–Ene Clickable Gelatin: A Platform Bioink for Multiple 3D Biofabrication Technologies,” Adv. Mater., vol. 29, no. 44, pp. 1–6, 2017, doi: 10.1002/adma.201703404.

X. Zhang, Y. Yang, J. Yao, Z. Shao, and X. Chen, “Strong collagen hydrogels by oxidized dextran modification,” ACS Sustain. Chem. Eng., vol. 2, no. 5, pp. 1318–1324, 2014, doi: 10.1021/sc500154t.

A. Lueckgen, D. S. Garske, A. Ellinghaus, D. J. Mooney, G. N. Duda, and A. Cipitria, “Enzymatically-degradable alginate hydrogels promote cell spreading and in vivo tissue infiltration,” Biomaterials, vol. 217, no. 5, p. 119294, 2019, doi: 10.1016/j.biomaterials.2019.119294.

J. P. Gong, Y. Katsuyama, T. Kurokawa, and Y. Osada, “Double-network hydrogels with extremely high mechanical strength,” Adv. Mater., vol. 15, no. 14, pp. 1155–1158, 2003, doi: 10.1002/adma.200304907.

Q. Chen, L. Zhu, C. Zhao, Q. Wang, and J. Zheng, “A robust, one-pot synthesis of highly mechanical and recoverable double network hydrogels using thermoreversible sol-gel polysaccharide,” Adv. Mater., vol. 25, no. 30, pp. 4171–4176, 2013, doi: 10.1002/adma.201300817.

D. Wu et al., “3D bioprinting of gellan gum and poly (ethylene glycol) diacrylate based hydrogels to produce human-scale constructs with high-fidelity,” Mater. Des., vol. 160, pp. 486–495, 2018, doi: 10.1016/j.matdes.2018.09.040.

H. Li, H. Zheng, Y. J. Tan, S. B. Tor, and K. Zhou, “Development of an Ultrastretchable Double-Network Hydrogel for Flexible Strain Sensors,” ACS Appl. Mater. Interfaces, vol. 13, no. 11, pp. 12814–12823, 2021, doi: 10.1021/acsami.0c19104.

A. Klein, P. G. Whitten, K. Resch, and G. Pinter, “Nanocomposite hydrogels: Fracture toughness and energy dissipation mechanisms,” J. Polym. Sci. Part B Polym. Phys., vol. 53, no. 24, pp. 1763–1773, 2015, doi: 10.1002/polb.23912.

M. Molina, M. Asadian-Birjand, J. Balach, J. Bergueiro, E. Miceli, and M. Calderón, “Stimuli-responsive nanogel composites and their application in nanomedicine,” Chem. Soc. Rev., vol. 44, no. 17, pp. 6161–6186, 2015, doi: 10.1039/c5cs00199d.

X. J. L. Xiao, C. Liu, J. Zhu, D. J. Pochan, “Hybrid, elastomeric hydrogels crosslinked by multifunctional block copolymer micelles,” Soft Matter, vol. 6, no. 21, pp. 5293–5297, 2010, doi: 10.1039/C0SM00511H.Hybrid.

K. Rahali et al., “Synthesis and characterization of nanofunctionalized gelatin methacrylate hydrogels,” Int. J. Mol. Sci., vol. 18, no. 12, pp. 2675–2690, 2017, doi: 10.3390/ijms18122675.

D. Chimene, L. Miller, L. M. Cross, M. K. Jaiswal, I. Singh, and A. K. Gaharwar, “Nanoengineered Osteoinductive Bioink for 3D Bioprinting Bone Tissue,” ACS Appl. Mater. Interfaces, vol. 12, no. 14, pp. 15976–15988, 2020, doi: 10.1021/acsami.9b19037.

D. G. Soares, E. A. F. Bordini, W. B. Swanson, C. A. de Souza Costa, and M. C. Bottino, Platform technologies for regenerative endodontics from multifunctional biomaterials to tooth-on-a-chip strategies, vol. 25, no. 8. Springer Berlin Heidelberg, 2021.

M. Altaii, L. Richards, and G. Rossi-Fedele, “Histological assessment of regenerative endodontic treatment in animal studies with different scaffolds: A systematic review,” Dent. Traumatol., vol. 33, no. 4, pp. 235–244, 2017, doi: 10.1111/edt.12338.

M. Rodriguez-Salvador and L. Ruiz-Cantu, “Revealing emerging science and technology research for dentistry applications of 3D bioprinting,” Int. J. Bioprinting, vol. 5, no. 1, pp. 1–8, 2019, doi: 10.18063/ijb.v5i1.170.

C. R. Silva et al., “Injectable and tunable hyaluronic acid hydrogels releasing chemotactic and angiogenic growth factors for endodontic regeneration,” Acta Biomater., vol. 77, pp. 155–171, 2018, doi: 10.1016/j.actbio.2018.07.035.

A. Athirasala et al., “A dentin-derived hydrogel bioink for 3D bioprinting of cell laden scaffolds for regenerative dentistry,” Biofabrication, vol. 10, no. 2, pp. 24101–24112, 2018, doi: 10.1088/1758-5090/aa9b4e.

G. Rasperini et al., “3D-printed Bioresorbable Scaffold for Periodontal Repair,” J. Dent. Res., vol. 94, no. 9, pp. 153S-157S, 2015, doi: 10.1177/0022034515588303.

N. Hassan, T. Krieg, M. Zinser, K. Schröder, and N. Kröger, “An Overview of Scaffolds and Biomaterials for Skin Expansion and Soft Tissue Regeneration : Insights on Zinc and Magnesium as New Potential Key Elements,” vol. 15, no. 19, pp. 3854–3890, 2023.

J. Han, W. Jeong, M. K. Kim, S. H. Nam, E. K. Park, and H. W. Kang, “Demineralized dentin matrix particle-based bio-ink for patient-specific shaped 3d dental tissue regeneration,” Polymers (Basel)., vol. 13, no. 8, 2021, doi: 10.3390/polym13081294.




How to Cite

Prebeg, T., Perić Kačarević, Željka, & Matijašić , G. (2023). Hybrid hydrogels for bioink development and potential use in dental tissue engineering . International Journal of Dental Biomaterials Research, 1, 22–29. https://doi.org/10.56939/DBR23122p




Most read articles by the same author(s)