Synthetic Matrix Metalloproteinase-Sensitive Hydrogels for the Conduction of Tissue Regeneration: Engineering Cell-Invasion Characteristics
Open accessAbstract
Synthetic hydrogels have been molecularly engineered to mimic the invasive characteristics of native provisional extracellular matrices: a combination of integrin-binding sites and substrates for matrix metalloproteinases (MMP) was required to render the networks degradable and invasive by cells via cell-secreted MMPs. Degradation of gels was engineered starting from a characterization of the degradation kinetics (k(cat) and K(m)) of synthetic MMP substrates in the soluble form and after crosslinking into a 3D hydrogel network. Primary human fibroblasts were demonstrated to proteolytically invade these networks, a process that depended on MMP substrate activity, adhesion ligand concentration, and network crosslinking density. Gels used to deliver recombinant human bone morphogenetic protein-2 to the site of critical defects in rat cranium were completely infiltrated by cells and remodeled into bony tissue within 4 wk at a dose of 5 microg per defect. Bone regeneration was also shown to depend on the proteolytic sensitivity of the matrices. These hydrogels may be useful in tissue engineering and cell biology as alternatives for naturally occurring extracellular matrix-derived materials such as fibrin or collagen.
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The inclusion of MMP-degradable crosslinkers enables more physiological proteolytic ECM remodeling by cancer cells.
“The inclusion of MMP-degradable crosslinkers also enables more physiological proteolytic ECM remodeling by cancer cells (Lutolf et al., 2003).”
From Three-dimensional modelling of ovarian cancer: from cell lines to organoids for discovery and personalized medicine (2022) · cites this paper as Lutolf et al., 2003
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- Authors
- Lutolf, M. P., Lauer-Fields, J. L., Schmoekel, H. G., Metters, A. T., Weber, F. E., Fields, G. B., & Hubbell, J. A.
- Affiliations
- Department of Materials and Institute for Biomedical Engineering, Swiss Federal Institute of Technology and University of Zurich, CH-8044 Zurich, Switzerland; Department of Chemistry and Biochemistry, Florida Atlantic University, Boca Raton, FL 33431-0991; Small Animal Surgery, University of Bern, CH-3012 Bern, Switzerland; and Department of Cranio-Maxillofacial Surgery, University Hospital Zurich, CH-8091 Zurich, Switzerland
- University of Bern (CH)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2003-04-09
- Volume
- 100
- Issue
- 9
- Pages
- 5413-5418
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC154359
- OpenAlex
- W2018818236
- Cited by
- 1,508
- References
- 42
- Citations by year
- 2026: 44 · 2025: 49 · 2024: 44 · 2023: 50 · 2022: 62 · 2021: 63 · 2020: 81 · 2019: 89 · 2018: 86 · 2017: 82 · 2016: 76 · 2015: 81 · 2014: 92 · 2013: 84 · 2012: 92
- FWCI
- 15.48
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
- Funders
- National Cancer Institute (R01CA098799)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Hydrogels: synthesis, properties, applications
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
- Keywords
- synthetic hydrogels, matrix metalloproteinases, cell invasion, extracellular matrix mimics, fibroblast invasion, crosslink density, bone regeneration, tissue regeneration, biomaterials
- MeSH terms
- Animals, Cells, Cultured, Humans, Kinetics, Skull, Fracture Healing, Rats, Sprague-Dawley, Hydrogel, Polyethylene Glycol Dimethacrylate, Matrix Metalloproteinases, Tissue Engineering, Rats
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