Controlled release of transforming growth factor-β3 from cartilage-extra-cellular-matrix-derived scaffolds to promote chondrogenesis of human-joint-tissue-derived stem cells

[Display omitted] The objective of this study was to develop a scaffold derived from cartilaginous extracellular matrix (ECM) that could be used as a growth factor delivery system to promote chondrogenesis of stem cells. Dehydrothermal crosslinked scaffolds were fabricated using a slurry of homogeni...

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Bibliographic Details
Published in:Acta biomaterialia 2014-10, Vol.10 (10), p.4400-4409
Main Authors: Almeida, Henrique V., Liu, Yurong, Cunniffe, Gráinne M., Mulhall, Kevin J., Matsiko, Amos, Buckley, Conor T., O’Brien, Fergal J., Kelly, Daniel J.
Format: Article
Language:English
Subjects:
Articular cartilage
Biomimetic Materials - chemistry
Biomimetic Materials - pharmacology
Cartilage, Articular - cytology
Cartilage, Articular - metabolism
Chondrogenesis - drug effects
Crosslinking
Delayed-Action Preparations - chemistry
Delayed-Action Preparations - pharmacology
Extracellular matrix
Extracellular Matrix - chemistry
Female
Humans
Hyaluronic Acid - chemistry
Hyaluronic Acid - pharmacology
Joints - cytology
Joints - metabolism
Male
Regeneration - drug effects
Stem cells
Stem Cells - cytology
Stem Cells - metabolism
Tissue engineering
Tissue Scaffolds - chemistry
Transforming Growth Factor beta3 - chemistry
Transforming Growth Factor beta3 - pharmacology
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Summary:[Display omitted] The objective of this study was to develop a scaffold derived from cartilaginous extracellular matrix (ECM) that could be used as a growth factor delivery system to promote chondrogenesis of stem cells. Dehydrothermal crosslinked scaffolds were fabricated using a slurry of homogenized porcine articular cartilage, which was then seeded with human infrapatellar-fat-pad-derived stem cells (FPSCs). It was found that these ECM-derived scaffolds promoted superior chondrogenesis of FPSCs when the constructs were additionally stimulated with transforming growth factor (TGF)-β3. Cell-mediated contraction of the scaffold was observed, which could be limited by the additional use of 1-ethyl-3-3dimethyl aminopropyl carbodiimide (EDAC) crosslinking without suppressing cartilage-specific matrix accumulation within the construct. To further validate the utility of the ECM-derived scaffold, we next compared its chondro-permissive properties to a biomimetic collagen–hyaluronic acid (HA) scaffold optimized for cartilage tissue engineering (TE) applications. The cartilage-ECM-derived scaffold supported at least comparable chondrogenesis to the collagen–HA scaffold, underwent less contraction and retained a greater proportion of synthesized sulfated glycosaminoglycans. Having developed a promising scaffold for TE, with superior chondrogenesis observed in the presence of exogenously supplied TGF-β3, the final phase of the study explored whether this scaffold could be used as a TGF-β3 delivery system to promote chondrogenesis of FPSCs. It was found that the majority of TGF-β3 that was loaded onto the scaffold was released in a controlled manner over the first 10days of culture, with comparable long-term chondrogenesis observed in these TGF-β3-loaded constructs compared to scaffolds where the TGF-β3 was continuously added to the media. The results of this study support the use of cartilage-ECM-derived scaffolds as a growth factor delivery system for use in articular cartilage regeneration.
ISSN:1742-7061
1878-7568
DOI:10.1016/j.actbio.2014.05.030