ArticleProceedings of the National Academy of Sciences of the United States of America2009
Two-component protein-engineered physical hydrogels for cell encapsulation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 124 papers.
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Who cites it
124 citing papers in PubMed.
- Microscale Mechanical Cues in Hydrogels: Engineering Strategies to Modulate Cell Fates in Three Dimensions.Cell biomaterials · 2026Article
- Engineering complexity into protein-based biomaterials for biomedical applications.Nature reviews. Materials · 2026Article
- An Overview of 3D Bioprinting Impact on Cell Viability: From Damage Assessment to Protection Solutions.Journal of functional biomaterials · 2025Review
- Molecular Engineering of Recombinant Protein Hydrogels: Programmable Design and Biomedical Applications.Gels (Basel, Switzerland) · 2025Review
- Highly Extensible Physically Crosslinked Hydrogels for High-Speed 3D Bioprinting.Advanced healthcare materials · 2025Article
- Engineered Protein Hydrogels as Biomimetic Cellular Scaffolds.Advanced materials (Deerfield Beach, Fla.) · 2024Review
- Emerging 2D Nanomaterials-Integrated Hydrogels: Advancements in Designing Theragenerative Materials for Bone Regeneration and Disease Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Review
- Biomimetic Non-ergodic Aging by Dynamic-to-covalent Transitions in Physical Hydrogels.ACS applied materials & interfaces · 2024Article
- Advancements in Regenerative Hydrogels in Skin Wound Treatment: A Comprehensive Review.International journal of molecular sciences · 2024Review
- Custom-engineered hydrogels for delivery of human iPSC-derived neurons into the injured cervical spinal cord.Biomaterials · 2024Article
- De novo design of modular protein hydrogels with programmable intra- and extracellular viscoelasticity.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Cancer cell response to extrinsic and intrinsic mechanical cue: opportunities for tumor apoptosis strategies.Regenerative biomaterials · 2024Review
- Natural and Engineered Isoforms of the Inflammasome Adaptor ASC Form Noncovalent, pH-Responsive Hydrogels.Biomacromolecules · 2023Article
- Chemical and Biological Engineering Strategies to Make and Modify Next-Generation Hydrogel Biomaterials.Matter · 2023Article
- Protein-Based Hydrogels and Their Biomedical Applications.Molecules (Basel, Switzerland) · 2023Review
- Self-healing hydrogel as an injectable implant: translation in brain diseases.Journal of biomedical science · 2023Review
- Accelerating aging with dynamic biomaterials: Recapitulating aged tissue phenotypes in engineered platforms.iScience · 2023Review
- Hydrogel-based microenvironment engineering of haematopoietic stem cells.Cellular and molecular life sciences : CMLS · 2023Review
- Directed assembly of genetically engineered eukaryotic cells into living functional materials via ultrahigh-affinity protein interactions.Science advances · 2022Article
- Clickable Polysaccharides for Biomedical Applications: A Comprehensive Review.Progress in polymer science · 2022Article
64 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Current protocols to encapsulate cells within physical hydrogels require substantial changes in environmental conditions (pH, temperature, or ionic strength) to initiate gelation. These conditions can be detrimental to cells and are often difficult to reproduce, therefore complicating their use in clinical settings. We report the development of a two-component, molecular-recognition gelation strategy that enables cell encapsulation without environmental triggers. Instead, the two components, which contain multiple repeats of WW and proline-rich peptide domains, undergo a sol-gel phase transition upon simple mixing and hetero-assembly of the peptide domains. We term these materials mixing-induced, two-component hydrogels. Our results demonstrate use of the WW and proline-rich domains in protein-engineered materials and expand the library of peptides successfully designed into engineered proteins. Because both of these association domains are normally found intracellularly, their molecular recognition is not disrupted by the presence of additional biomolecules in the extracellular milieu, thereby enabling reproducible encapsulation of multiple cell types, including PC-12 neuronal-like cells, human umbilical vein endothelial cells, and murine adult neural stem cells. Precise variations in the molecular-level design of the two components including (i) the frequency of repeated association domains per chain and (ii) the association energy between domains enable tailoring of the hydrogel viscoelasticity to achieve plateau shear moduli ranging from approximately 9 to 50 Pa. Because of the transient physical crosslinks that form between association domains, these hydrogels are shear-thinning, injectable, and self-healing. Neural stem cells encapsulated in the hydrogels form stable three-dimensional cultures that continue to self-renew, differentiate, and sprout extended neurites.
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