Designing degradable hydrogels for orthogonal control of cell microenvironments
Open accessAbstract
Degradable and cell-compatible hydrogels can be designed to mimic the physical and biochemical characteristics of native extracellular matrices and provide tunability of degradation rates and related properties under physiological conditions. Hence, such hydrogels are finding widespread application in many bioengineering fields, including controlled bioactive molecule delivery, cell encapsulation for controlled three-dimensional culture, and tissue engineering. Cellular processes, such as adhesion, proliferation, spreading, migration, and differentiation, can be controlled within degradable, cell-compatible hydrogels with temporal tuning of biochemical or biophysical cues, such as growth factor presentation or hydrogel stiffness. However, thoughtful selection of hydrogel base materials, formation chemistries, and degradable moieties is necessary to achieve the appropriate level of property control and desired cellular response. In this review, hydrogel design considerations and materials for hydrogel preparation, ranging from natural polymers to synthetic polymers, are overviewed. Recent advances in chemical and physical methods to crosslink hydrogels are highlighted, as well as recent developments in controlling hydrogel degradation rates and modes of degradation. Special attention is given to spatial or temporal presentation of various biochemical and biophysical cues to modulate cell response in static (i.e., non-degradable) or dynamic (i.e., degradable) microenvironments. This review provides insight into the design of new cell-compatible, degradable hydrogels to understand and modulate cellular processes for various biomedical applications.
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Synthetic hydrogels may degrade into cytotoxic by-products or require cytotoxic initiators, limiting the types of polymers that can be used in cell culture.
“Further, synthetic hydrogels may degrade into cytotoxic by-products184 or require cytotoxic initiators185, limiting the types of polymers that can be used in cell culture186.”
From Towards organoid culture without Matrigel (2021) · cites this paper as [186]
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- Authors
- Kharkar, P. M., Kiick, K. L., & Kloxin, A. M.
- Affiliations
- University of Delaware (US)
- Delaware Biotechnology Institute (US)
- Corresponding author
- Kiick, Kristi L.
- Kloxin, April M.
- Venue
- Chem. Soc. Rev.
- Publisher
- Royal Society of Chemistry (RSC)
- Published
- 2013-04-22
- Volume
- 42
- Issue
- 17
- Pages
- 7335-7372
- ISSN
- 0306-0012 (ISSN-L)
- 1460-4744
- PMC
- PMC3762890
- OpenAlex
- W2036827000
- Cited by
- 717
- References
- 378
- Citations by year
- 2026: 39 · 2025: 49 · 2024: 56 · 2023: 63 · 2022: 53 · 2021: 64 · 2020: 66 · 2019: 59 · 2018: 64 · 2017: 56 · 2016: 56 · 2015: 48 · 2014: 35 · 2013: 8
- FWCI
- 3.05
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc
- Locations
- Chemical Society Reviews (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Funders
- National Science Foundation (CAREER)
- National Aeronautics and Space Administration
- University of Delaware Research Foundation
- University of Delaware
- California Institute of Technology
- University of Georgia
- National Institutes of Health (8p20gm103541-10)
- U.S. Public Health Service (P2012A01377)
- University of Massachusetts Amherst
- National Defense Science and Engineering Graduate
- National Institute on Deafness and Other Communication Disorders (R01-DC011377A, R01DC011377)
- National Institute of General Medical Sciences (P20-GM103541)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Hydrogels: synthesis, properties, applications
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Keywords
- biodegradable hydrogels, cell microenvironment, hydrogel design, hydrogel degradation, hydrogel crosslinking, extracellular matrix mimics, growth factor presentation, hydrogel stiffness, cell encapsulation, 3D cell culture, bioactive compound delivery, natural polymers, synthetic polymers, cell adhesion and migration, tissue engineering
- MeSH terms
- Biocompatible Materials, Humans, Polymers, Extracellular Matrix Proteins, Hydrogels, Tissue Engineering, Cellular Microenvironment
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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