Bio‐Orthogonally Crosslinked, Engineered Protein Hydrogels with Tunable Mechanics and Biochemistry for Cell Encapsulation
Open accessAbstract
Covalently‐crosslinked hydrogels are commonly used as 3D matrices for cell culture and transplantation. However, the crosslinking chemistries used to prepare these gels generally cross‐react with functional groups present on the cell surface, potentially leading to cytotoxicity and other undesired effects. Bio‐orthogonal chemistries have been developed that do not react with biologically relevant functional groups, thereby preventing these undesirable side reactions. However, previously developed biomaterials using these chemistries still possess less than ideal properties for cell encapsulation, such as slow gelation kinetics and limited tuning of matrix mechanics and biochemistry. Here, engineered elastin‐like proteins (ELPs) are developed that crosslink via strain‐promoted azide‐alkyne cycloaddition (SPAAC) or Staudinger ligation. The SPAAC‐crosslinked materials form gels within seconds and complete gelation within minutes. These hydrogels support the encapsulation and phenotypic maintenance of human mesenchymal stem cells, human umbilical vein endothelial cells, and murine neural progenitor cells. SPAAC‐ELP gels exhibit independent tuning of stiffness and cell adhesion, with significantly improved cell viability and spreading observed in materials containing a fibronectin‐derived arginine‐glycine‐aspartic acid (RGD) domain. The crosslinking chemistry used permits further material functionalization, even in the presence of cells and serum. These hydrogels are anticipated to be useful in a wide range of applications, including therapeutic cell delivery and bioprinting.
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Recombinant proteins are molecularly well-defined and can be tuned independently for stiffness, viscoelastic behavior, and chemical functionality.
“Recombinant proteins are molecularly well-defined and can be tuned independently for stiffness, viscoelastic behavior, and chemical functionality203–205.”
From Towards organoid culture without Matrigel (2021) · cites this paper as [203]
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Towards organoid culture without Matrigel
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- Authors
- Madl, C. M., Katz, L. M., & Heilshorn, S. C.
- Affiliations
- Stanford University (US)
- Corresponding author
- Heilshorn, Sarah C.
- Venue
- Advanced Functional Materials
- Publisher
- Wiley
- Published
- 2016-03-21
- Volume
- 26
- Issue
- 21
- Pages
- 3612-3620
- ISSN
- 1616-301X (ISSN-L)
- 1616-3028
- PMC
- PMC5019573
- OpenAlex
- W2310756979
- Cited by
- 156
- References
- 62
- Citations by year
- 2026: 5 · 2025: 11 · 2024: 18 · 2023: 10 · 2022: 10 · 2021: 20 · 2020: 30 · 2019: 14 · 2018: 27 · 2017: 11
- FWCI
- 8.45
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Advanced Functional Materials (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases (U19AI116484)
- National Institute of Biomedical Imaging and Bioengineering (R21EB018407, F31EB020502)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Hydrogels: synthesis, properties, applications
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Physical Sciences › Materials Science › Biomaterials › Supramolecular Self-Assembly in Materials
- Keywords
- protein hydrogels, strain-promoted azide-alkyne cycloaddition, Staudinger ligation, cell encapsulation, hydrogel stiffness, cell adhesion, RGD peptide, mesenchymal stem cells, endothelial cells, neural progenitor cells, cell delivery, bioprinting, gelation kinetics
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