The effects of crosslinking of scaffolds engineered from cartilage ECM on the chondrogenic differentiation of MSCs
Open accessAbstract
Scaffolds fabricated from cartilage extracellular matrix provide a chondroinductive environment that stimulates cartilaginous matrix synthesis in a variety of cell types. A limitation of these cartilage-derived matrix (CDM) scaffolds is that they contract during in vitro culture, which unpredictably alters their shape. The current study examined the hypothesis that collagen crosslinking techniques could inhibit cell-mediated contraction of CDM scaffolds. We analyzed the effects of dehydrothermal (DHT) treatment, ultraviolet light irradiation (UV), and the chemical crosslinker carbodiimide (CAR) on scaffold contraction and chondrogenic differentiation of adult human bone marrow-derived stem cells (MSCs). Both physical and chemical crosslinking treatments retained the original scaffold dimensions. DHT and UV treatments produced significantly higher glycosaminoglycan and collagen contents than CAR crosslinked and non-crosslinked constructs. Crosslinking treatments influenced the composition of newly synthesized matrix, and DHT treatment best matched the composition of native cartilage. DHT, UV, and non-crosslinked CDM films supported cell attachment, while CAR crosslinking inhibited cell adhesion. These results affirm that collagen crosslinking treatments can prevent cell-mediated contraction of CDM scaffolds. Interestingly, crosslinking treatments influence chondrogenic differentiation. These effects seem to be mediated by modifications to cell-matrix interactions between MSCs and the CDM; however, further work is necessary to elucidate the specific mechanisms involved in this process.
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Cross-linking agents have been successfully employed to enhance enzymatic resistance, matrix decomposition, and ultimately improve biomechanical strength in various tissues and organs.
“Cross-linking agents have been successfully employed to enhance enzymatic resistance, matrix decomposition, and ultimately improve biomechanical strength in various tissues and organs [[171], [172], [173]].”
From Liver tissue engineering using decellularized scaffolds: Current progress, challenges, and opportunities (2024) · cites this paper as [171]
The Introduction says crosslinking treatments influence scaffold mechanical strength and resistance to enzymatic degradation, supporting those parts of the claim. It does not say they enhance matrix decomposition; resistance to degradation points in the opposite direction. The Discussion also says this study did not quantitatively assess mechanical properties, so it does not establish improved biomechanical strength across various tissues and organs. (LLM, conf=0.85)
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- Authors
- Rowland, C. R., Lennon, D. P., Caplan, A. I., & Guilak, F.
- Affiliations
- Duke Medical Center (US)
- Case Western Reserve University (US)
- Corresponding author
- Guilak, Farshid
- Venue
- Biomaterials
- Publisher
- Elsevier BV
- Published
- 2013-07
- Volume
- 34
- Issue
- 23
- Pages
- 5802-5812
- ISSN
- 0142-9612 (ISSN-L)
- PMC
- PMC3660461
- OpenAlex
- W2021219047
- Cited by
- 190
- References
- 70
- Citations by year
- 2026: 6 · 2025: 4 · 2024: 10 · 2023: 14 · 2022: 14 · 2021: 18 · 2020: 14 · 2019: 23 · 2018: 18 · 2017: 12 · 2016: 16 · 2015: 22 · 2014: 14 · 2013: 3
- FWCI
- 16.69
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Biomaterials (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (AG 15768, R01AG015768)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR 50245, AR48182, AR-48852, P01AR050245, R01AR048852, P01AR053622, AR53622, R01AR048182)
- Topics
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Hydrogels: synthesis, properties, applications
- Health Sciences › Medicine › Rheumatology › Osteoarthritis Treatment and Mechanisms
- Keywords
- collagen cross-linking, chondrogenic differentiation, mesenchymal stem cells, dehydrothermal treatment, UV irradiation, carbodiimide crosslinking, cell adhesion, cell-matrix interactions, glycosaminoglycans, collagen, cartilage tissue engineering
- MeSH terms
- Adult, Animals, Cartilage, Cell Adhesion, Cell Differentiation, Collagen, Cross-Linking Reagents, DNA, Extracellular Matrix, Female, Glycosaminoglycans, Humans, Immunohistochemistry, Porosity, Chondrogenesis, Tissue Engineering, Sus scrofa, Green Fluorescent Proteins, Transforming Growth Factor beta3, Tissue Scaffolds, Mesenchymal Stem Cells
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