Viscoelastic Oxidized Alginates with Reversible Imine Type Crosslinks: Self-Healing, Injectable, and Bioprintable Hydrogels
Bioprinting techniques allow for the recreation of 3D tissue-like structures. By deposition of hydrogels combined with cells (bioinks) in a spatially controlled way, one can create complex and multiscale structures. Despite this promise, the ability to deposit customizable cell-laden structures for...
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| Format: | Article |
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MDPI AG
2018-11-01
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| Series: | Gels |
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| Online Access: | https://www.mdpi.com/2310-2861/4/4/85 |
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| author | Shahzad Hafeez Huey Wen Ooi Francis L. C. Morgan Carlos Mota Monica Dettin Clemens van Blitterswijk Lorenzo Moroni Matthew B. Baker |
| author_facet | Shahzad Hafeez Huey Wen Ooi Francis L. C. Morgan Carlos Mota Monica Dettin Clemens van Blitterswijk Lorenzo Moroni Matthew B. Baker |
| author_sort | Shahzad Hafeez |
| collection | DOAJ |
| description | Bioprinting techniques allow for the recreation of 3D tissue-like structures. By deposition of hydrogels combined with cells (bioinks) in a spatially controlled way, one can create complex and multiscale structures. Despite this promise, the ability to deposit customizable cell-laden structures for soft tissues is still limited. Traditionally, bioprinting relies on hydrogels comprised of covalent or mostly static crosslinks. Yet, soft tissues and the extracellular matrix (ECM) possess viscoelastic properties, which can be more appropriately mimicked with hydrogels containing reversible crosslinks. In this study, we have investigated aldehyde containing oxidized alginate (ox-alg), combined with different cross-linkers, to develop a small library of viscoelastic, self-healing, and bioprintable hydrogels. By using distinctly different imine-type dynamic covalent chemistries (DCvC), (oxime, semicarbazone, and hydrazone), rational tuning of rheological and mechanical properties was possible. While all materials showed biocompatibility, we observed that the nature of imine type crosslink had a marked influence on hydrogel stiffness, viscoelasticity, self-healing, cell morphology, and printability. The semicarbazone and hydrazone crosslinks were found to be viscoelastic, self-healing, and printable—without the need for additional Ca<sup>2+</sup> crosslinking—while also promoting the adhesion and spreading of fibroblasts. In contrast, the oxime cross-linked gels were found to be mostly elastic and showed neither self-healing, suitable printability, nor fibroblast spreading. The semicarbazone and hydrazone gels hold great potential as dynamic 3D cell culture systems, for therapeutics and cell delivery, and a newer generation of smart bioinks. |
| first_indexed | 2024-04-12T23:06:25Z |
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| institution | Directory Open Access Journal |
| issn | 2310-2861 |
| language | English |
| last_indexed | 2024-04-12T23:06:25Z |
| publishDate | 2018-11-01 |
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| series | Gels |
| spelling | doaj.art-ef635dfd05ed4fe88e9c9535fa2799982022-12-22T03:12:54ZengMDPI AGGels2310-28612018-11-01448510.3390/gels4040085gels4040085Viscoelastic Oxidized Alginates with Reversible Imine Type Crosslinks: Self-Healing, Injectable, and Bioprintable HydrogelsShahzad Hafeez0Huey Wen Ooi1Francis L. C. Morgan2Carlos Mota3Monica Dettin4Clemens van Blitterswijk5Lorenzo Moroni6Matthew B. Baker7Department of Complex Tissue Regeneration, MERLN Institute for Technology Inspired Regenerative Medicine, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The NetherlandsDepartment of Complex Tissue Regeneration, MERLN Institute for Technology Inspired Regenerative Medicine, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The NetherlandsDepartment of Complex Tissue Regeneration, MERLN Institute for Technology Inspired Regenerative Medicine, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The NetherlandsDepartment of Complex Tissue Regeneration, MERLN Institute for Technology Inspired Regenerative Medicine, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The NetherlandsDepartment of Industrial Engineering, University of Padua, 35131 Padua, ItalyDepartment of Complex Tissue Regeneration, MERLN Institute for Technology Inspired Regenerative Medicine, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The NetherlandsDepartment of Complex Tissue Regeneration, MERLN Institute for Technology Inspired Regenerative Medicine, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The NetherlandsDepartment of Complex Tissue Regeneration, MERLN Institute for Technology Inspired Regenerative Medicine, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The NetherlandsBioprinting techniques allow for the recreation of 3D tissue-like structures. By deposition of hydrogels combined with cells (bioinks) in a spatially controlled way, one can create complex and multiscale structures. Despite this promise, the ability to deposit customizable cell-laden structures for soft tissues is still limited. Traditionally, bioprinting relies on hydrogels comprised of covalent or mostly static crosslinks. Yet, soft tissues and the extracellular matrix (ECM) possess viscoelastic properties, which can be more appropriately mimicked with hydrogels containing reversible crosslinks. In this study, we have investigated aldehyde containing oxidized alginate (ox-alg), combined with different cross-linkers, to develop a small library of viscoelastic, self-healing, and bioprintable hydrogels. By using distinctly different imine-type dynamic covalent chemistries (DCvC), (oxime, semicarbazone, and hydrazone), rational tuning of rheological and mechanical properties was possible. While all materials showed biocompatibility, we observed that the nature of imine type crosslink had a marked influence on hydrogel stiffness, viscoelasticity, self-healing, cell morphology, and printability. The semicarbazone and hydrazone crosslinks were found to be viscoelastic, self-healing, and printable—without the need for additional Ca<sup>2+</sup> crosslinking—while also promoting the adhesion and spreading of fibroblasts. In contrast, the oxime cross-linked gels were found to be mostly elastic and showed neither self-healing, suitable printability, nor fibroblast spreading. The semicarbazone and hydrazone gels hold great potential as dynamic 3D cell culture systems, for therapeutics and cell delivery, and a newer generation of smart bioinks.https://www.mdpi.com/2310-2861/4/4/85dynamic hydrogeldynamic covalent chemistry (DCvC)reversible bondsbioprinting (BP)oxidized alginate (ox-alg)tissue engineeringviscoelastichydrazonesemicarbazoneoxime |
| spellingShingle | Shahzad Hafeez Huey Wen Ooi Francis L. C. Morgan Carlos Mota Monica Dettin Clemens van Blitterswijk Lorenzo Moroni Matthew B. Baker Viscoelastic Oxidized Alginates with Reversible Imine Type Crosslinks: Self-Healing, Injectable, and Bioprintable Hydrogels Gels dynamic hydrogel dynamic covalent chemistry (DCvC) reversible bonds bioprinting (BP) oxidized alginate (ox-alg) tissue engineering viscoelastic hydrazone semicarbazone oxime |
| title | Viscoelastic Oxidized Alginates with Reversible Imine Type Crosslinks: Self-Healing, Injectable, and Bioprintable Hydrogels |
| title_full | Viscoelastic Oxidized Alginates with Reversible Imine Type Crosslinks: Self-Healing, Injectable, and Bioprintable Hydrogels |
| title_fullStr | Viscoelastic Oxidized Alginates with Reversible Imine Type Crosslinks: Self-Healing, Injectable, and Bioprintable Hydrogels |
| title_full_unstemmed | Viscoelastic Oxidized Alginates with Reversible Imine Type Crosslinks: Self-Healing, Injectable, and Bioprintable Hydrogels |
| title_short | Viscoelastic Oxidized Alginates with Reversible Imine Type Crosslinks: Self-Healing, Injectable, and Bioprintable Hydrogels |
| title_sort | viscoelastic oxidized alginates with reversible imine type crosslinks self healing injectable and bioprintable hydrogels |
| topic | dynamic hydrogel dynamic covalent chemistry (DCvC) reversible bonds bioprinting (BP) oxidized alginate (ox-alg) tissue engineering viscoelastic hydrazone semicarbazone oxime |
| url | https://www.mdpi.com/2310-2861/4/4/85 |
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