Gel structure has an impact on pericellular and extracellular matrix deposition, which subsequently alters metabolic activities in chondrocyte-laden PEG hydrogels
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While designing poly(ethylene glycol) hydrogels with high moduli suitable for in situ placement is attractive for cartilage regeneration, the impact of a tighter crosslinked structure on the organization and deposition of the matrix is not fully understood. The objectives of this study were to characterize the composition and spatial organization of new matrix as a function of gel crosslinking and study its impact on chondrocytes in terms of anabolic and catabolic gene expression and catabolic activity. Bovine articular chondrocytes were encapsulated in hydrogels with three crosslinking densities (compressive moduli 60, 320 and 590 kPa) and cultured for 25 days. Glycosaminoglycan production increased with culture time and was greatest in the gels with lowest crosslinking. Collagens II and VI, aggrecan, link protein and decorin were localized to pericellular regions in all gels, but their presence decreased with increasing gel crosslinking. Collagen II and aggrecan expression were initially up-regulated in gels with higher crosslinking, but increased similarly up to day 15. Matrix metalloproteinase (MMP)-1 and MMP-13 expression were elevated (∼25-fold) in gels with higher crosslinking throughout the study, while MMP-3 was unaffected by gel crosslinking. The presence of aggrecan and collagen degradation products confirmed MMP activity. These findings indicate that chondrocytes synthesized the major cartilage components within PEG hydrogels, however, gel structure had a significant impact on the composition and spatial organization of the new tissue and on how chondrocytes responded to their environment, particularly with respect to their catabolic expression.
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Softer hydrogels have shown more promise for enhancing cell survival and extracellular matrix elaboration due to larger mesh size.
“The softer hydrogels have also shown more promise with enhancing cell survival and extracellular matrix elaboration due to the larger mesh size, making them even more attractive.60–64”
From Student award winner in the undergraduate category for the society of biomaterials 9th World Biomaterials Congress, Chengdu, China, June 1–5, 2012: The effects of substrate stiffness on the <i>in vitro</i> activation of macrophages and <i>in vivo</i> host response to poly(ethylene glycol)‐based hydrogels (2012) · cites this paper as [63]
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Self-citation
- Authors
- Nicodemus, G. D., Skaalure, S. C., & Bryant, S. J.
- Affiliations
- University of Colorado Boulder (US)
- Corresponding author
- Bryant, S.J.
- Venue
- Acta Biomaterialia
- Publisher
- Elsevier BV
- Published
- 2011-02
- Volume
- 7
- Issue
- 2
- Pages
- 492-504
- ISSN
- 1742-7061 (ISSN-L)
- PMC
- PMC3014397
- OpenAlex
- W2001786080
- Cited by
- 98
- References
- 63
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 2 · 2023: 8 · 2022: 3 · 2021: 6 · 2020: 8 · 2019: 6 · 2018: 8 · 2017: 8 · 2016: 10 · 2015: 7 · 2014: 7 · 2013: 8 · 2012: 7
- FWCI
- 2.69
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Acta Biomaterialia (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute of Dental and Craniofacial Research (K22DE016608)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Hydrogels: synthesis, properties, applications
- Health Sciences › Medicine › Rheumatology › Osteoarthritis Treatment and Mechanisms
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Keywords
- poly(ethylene glycol) hydrogels, chondrocytes, cartilage regeneration, pericellular matrix, extracellular matrix deposition, glycosaminoglycan production, type II collagen, aggrecan, MMP-1, MMP-13, MMP-3, catabolic gene expression, compressive modulus
- MeSH terms
- Animals, Cattle, Cross-Linking Reagents, Extracellular Matrix, Gene Expression Regulation, Glycosaminoglycans, Immunohistochemistry, Methacrylates, Peptide Fragments, Polyethylene Glycols, Proteoglycans, Solubility, Extracellular Matrix Proteins, Chondrocytes, Hydrogels
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