Cited by 717Hydrogels: synthesis, properties, applications3D Printing in Biomedical ResearchCellular Mechanics and Interactions

Designing degradable hydrogels for orthogonal control of cell microenvironments

Open access
Kharkar, Prathamesh M., Kiick, Kristi L., Kloxin, April M.·2013·Chem. Soc. Rev.

Abstract

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.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1039/c3cs60040h

Cites

378 of 378 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • 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]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

2 retracted

Flagged first, then by citations

Research works printed but not linked: 12

  1. Zhao J., in Chitosan-based hydrogels: functions and applications, ed. K. Yao, J. Li, F. Yao and Y. Yin, CRC Press, 2012.
  2. McGann C. and Kiick K., in Engineering Biomaterials for Regenerative Medicine: Novel Technologies for Clinical Applications, ed. S. K. Bhatia, Springer, 2011.
  3. Cash B. D. Lacy B. E. Gastroenterol. Hepatol. 2006 2 736 749 PMC5358085 28325992
  4. Michalek J., Hobzova R., Pradny M. and Duskova M., in Biomedical Applications of Hydrogels Handbook, ed. R. M. Ottenbrite, K. Park and T. Okano, Springer, New York, 2010, pp. 303–315.
  5. Fairbanks B. D. Schwartz M. P. Halevi A. E. Nuttelman C. R. Bowman C. N. Anseth K. S. Adv. Mater. 2009 21 5005 5010 25377720 PMC4226179
  6. Malkoch M. Vestberg R. Gupta N. Mespouille L. Dubois P. Mason A. F. Hedrick J. L. Liao Q. Frank C. W. Kingsbury K. Hawker C. J. Chem. Commun. 2006 2774 17009459
  7. Jewett J. C. Bertozzi C. R. Chem. Soc. Rev. 2010 39 1272 1279 20349533 PMC2865253
  8. Fairbanks B. D. Schwartz M. P. Halevi A. E. Nuttelman C. R. Bowman C. N. Anseth K. S. Adv. Mater. 2009 21 5005 5010 25377720 PMC4226179
  9. Anderson S. B. Lin C. C. Kuntzler D. V. Anseth K. S. Biomaterials 2011 32 3564 3574 21334063 PMC3085912
  10. Nuttelman C. R., Kloxin A. M. and Anseth K. S., in Tissue Eng, ed. J. P. Fisher, Springer-Verlag Berlin, Berlin, 2006, vol. 585, pp. 135–149.
  11. Patterson J. Siew R. Herring S. W. Lin A. S. Guldberg R. Stayton P. S. Biomaterials 2010 31 6772 6781 20573393 PMC2907529
  12. Fairbanks B. D. Singh S. P. Bowman C. N. Anseth K. S. Macromolecules 2011 44 2444 2450 21512614 PMC3079292

Cited by

Sorted by citations

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.
Published
2013-04-22
Volume
42
Issue
17
Pages
7335-7372
ISSN
  • 0306-0012 (ISSN-L)
  • 1460-4744
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
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 ›

Are you an author, or do you see a problem with this page? Request a review