Microstructured click hydrogels for cell contact guidance in 3D
The topography of the extracellular matrix (ECM) is a major biophysical regulator of cell behavior. While this has inspired the design of cell-instructive biomaterials, the ability to present topographic cues to cells in a true 3D setting remains challenging, particularly in ECM-like hydrogels made...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-04-01
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| Series: | Materials Today Bio |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2590006423000649 |
| _version_ | 1797854313225125888 |
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| author | Mariana I. Neves Sílvia J. Bidarra Mariana V. Magalhães Ana L. Torres Lorenzo Moroni Cristina C. Barrias |
| author_facet | Mariana I. Neves Sílvia J. Bidarra Mariana V. Magalhães Ana L. Torres Lorenzo Moroni Cristina C. Barrias |
| author_sort | Mariana I. Neves |
| collection | DOAJ |
| description | The topography of the extracellular matrix (ECM) is a major biophysical regulator of cell behavior. While this has inspired the design of cell-instructive biomaterials, the ability to present topographic cues to cells in a true 3D setting remains challenging, particularly in ECM-like hydrogels made from a single polymer. Herein, we report the design of microstructured alginate hydrogels for injectable cell delivery and show their ability to orchestrate morphogenesis via cellular contact guidance in 3D. Alginate was grafted with hydrophobic cyclooctyne groups (ALG-K), yielding amphiphilic derivatives with self-associative potential and ionic crosslinking ability. This allowed the formation of microstructured ALG-KH hydrogels, triggered by the spontaneous segregation between hydrophobic/hydrophilic regions of the polymer that generated 3D networks with stiffer microdomains within a softer lattice. The azide-reactivity of cyclooctynes also allowed ALG-K functionalization with bioactive peptides via cytocompatible strain-promoted azide-alkyne cycloaddition (SPAAC). Hydrogel-embedded mesenchymal stem cells (MSCs) were able to integrate spatial information and to mechano-sense the 3D topography, which regulated cell shape and stress fiber organization. MSCs clusters initially formed on microstructured regions could then act as seeds for neo-tissue formation, inducing cells to produce their own ECM and self-organize into multicellular structures throughout the hydrogel. By combining 3D topography, click functionalization, and injectability, using a single polymer, ALG-K hydrogels provide a unique cell delivery platform for tissue regeneration. |
| first_indexed | 2024-04-09T20:03:57Z |
| format | Article |
| id | doaj.art-18edb1975891429986786bab18bad213 |
| institution | Directory Open Access Journal |
| issn | 2590-0064 |
| language | English |
| last_indexed | 2024-04-09T20:03:57Z |
| publishDate | 2023-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Materials Today Bio |
| spelling | doaj.art-18edb1975891429986786bab18bad2132023-04-02T06:15:03ZengElsevierMaterials Today Bio2590-00642023-04-0119100604Microstructured click hydrogels for cell contact guidance in 3DMariana I. Neves0Sílvia J. Bidarra1Mariana V. Magalhães2Ana L. Torres3Lorenzo Moroni4Cristina C. Barrias5i3S – Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal; INEB – Instituto de Engenharia Biomédica, Universidade do Porto, Portugal; FEUP – Faculdade de Engenharia, Universidade do Porto, Portugali3S – Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal; INEB – Instituto de Engenharia Biomédica, Universidade do Porto, Portugali3S – Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugali3S – Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal; INEB – Instituto de Engenharia Biomédica, Universidade do Porto, PortugalDepartment of Complex Tissue Regeneration, MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, Maastricht, Netherlands; CNR NANOTEC - Institute of Nanotechnology, Università del Salento, Lecce, Italyi3S – Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal; INEB – Instituto de Engenharia Biomédica, Universidade do Porto, Portugal; ICBAS – Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Portugal; Corresponding author. i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135, Porto, Portugal.The topography of the extracellular matrix (ECM) is a major biophysical regulator of cell behavior. While this has inspired the design of cell-instructive biomaterials, the ability to present topographic cues to cells in a true 3D setting remains challenging, particularly in ECM-like hydrogels made from a single polymer. Herein, we report the design of microstructured alginate hydrogels for injectable cell delivery and show their ability to orchestrate morphogenesis via cellular contact guidance in 3D. Alginate was grafted with hydrophobic cyclooctyne groups (ALG-K), yielding amphiphilic derivatives with self-associative potential and ionic crosslinking ability. This allowed the formation of microstructured ALG-KH hydrogels, triggered by the spontaneous segregation between hydrophobic/hydrophilic regions of the polymer that generated 3D networks with stiffer microdomains within a softer lattice. The azide-reactivity of cyclooctynes also allowed ALG-K functionalization with bioactive peptides via cytocompatible strain-promoted azide-alkyne cycloaddition (SPAAC). Hydrogel-embedded mesenchymal stem cells (MSCs) were able to integrate spatial information and to mechano-sense the 3D topography, which regulated cell shape and stress fiber organization. MSCs clusters initially formed on microstructured regions could then act as seeds for neo-tissue formation, inducing cells to produce their own ECM and self-organize into multicellular structures throughout the hydrogel. By combining 3D topography, click functionalization, and injectability, using a single polymer, ALG-K hydrogels provide a unique cell delivery platform for tissue regeneration.http://www.sciencedirect.com/science/article/pii/S2590006423000649Physical cuesCell instructiveProtein sequestrationCell therapyTissue engineeringRegenerative medicine |
| spellingShingle | Mariana I. Neves Sílvia J. Bidarra Mariana V. Magalhães Ana L. Torres Lorenzo Moroni Cristina C. Barrias Microstructured click hydrogels for cell contact guidance in 3D Materials Today Bio Physical cues Cell instructive Protein sequestration Cell therapy Tissue engineering Regenerative medicine |
| title | Microstructured click hydrogels for cell contact guidance in 3D |
| title_full | Microstructured click hydrogels for cell contact guidance in 3D |
| title_fullStr | Microstructured click hydrogels for cell contact guidance in 3D |
| title_full_unstemmed | Microstructured click hydrogels for cell contact guidance in 3D |
| title_short | Microstructured click hydrogels for cell contact guidance in 3D |
| title_sort | microstructured click hydrogels for cell contact guidance in 3d |
| topic | Physical cues Cell instructive Protein sequestration Cell therapy Tissue engineering Regenerative medicine |
| url | http://www.sciencedirect.com/science/article/pii/S2590006423000649 |
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