title: Stem cells display a donor dependent response to escalating levels of growth factor release from extracellular matrix-derived scaffolds.
abstract: Numerous growth factor delivery systems have been developed for tissue engineering. However, little is known about how the dose of a specific protein will influence tissue regeneration, or how different patients will respond to altered levels of growth factor presentation. The objective of the present study was to assess stem cell chondrogenesis within extracellular-matrix (ECM)-derived scaffolds loaded with escalating levels of transforming growth factor (TGF)-β3. It was also sought to determine if stem cells display a donor-dependent response to different doses of TGF-β3, from low (5 ng) to high (200 ng), released from such scaffolds. It was found that ECM-derived scaffolds possess the capacity to bind and release increasing amounts of TGF-β3, with between 60% and 75% of this growth factor released into the media over the first 12 days of culture. After seeding these scaffolds with human infrapatellar fat pad-derived stem cells (FPSCs), it was found that cartilage-specific ECM accumulation was greatest for the higher levels of growth factor loading. Importantly, soak-loading cartilage ECM-derived scaffolds with high levels of TGF-β3 always resulted in at least comparable levels of chondrogenesis to controls where this growth factor was continuously added to the culture media. Similar results were observed for FPSCs from all donors, although the absolute level of secreted matrix did vary from donor to donor. Therefore, while no single growth factor release profile will be optimal for all patients, the results of this study suggest that the combination of a highly porous cartilage ECM-derived scaffold coupled with appropriate levels of TGF-β3 can consistently drive chondrogenesis of adult stem cells. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: Trinity Centre for Bioengineering, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.|Department of Mechanical and Manufacturing Engineering, School of Engineering, Trinity College Dublin, Dublin, Ireland.
authors.forename: Henrique V
authors.initials: HV
authors.lastname: Almeida
authors.affiliation: Sports Surgery Clinic, Santry, Dublin, Ireland.
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Mulhall
authors.affiliation: Trinity Centre for Bioengineering, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.|Advanced Materials and Bioengineering Research Centre (AMBER), Trinity College Dublin & Royal College of Surgeons in Ireland, Dublin, Ireland.|Tissue Engineering Research Group, Department of Anatomy, Royal College of Surgeons in Ireland, Dublin, Ireland.
authors.forename: Fergal J
authors.initials: FJ
authors.lastname: O'Brien
authors.affiliation: Trinity Centre for Bioengineering, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.|Department of Mechanical and Manufacturing Engineering, School of Engineering, Trinity College Dublin, Dublin, Ireland.|Advanced Materials and Bioengineering Research Centre (AMBER), Trinity College Dublin & Royal College of Surgeons in Ireland, Dublin, Ireland.|Tissue Engineering Research Group, Department of Anatomy, Royal College of Surgeons in Ireland, Dublin, Ireland.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Kelly
mesh_terms: D000328:Adult; D053687:Adult Stem Cells / Q000166:cytology / Q000378:metabolism*; D000368:Aged; D005109:Extracellular Matrix / Q000737:chemistry*; D005260:Female; D006801:Humans; D008297:Male; D054457:Tissue Scaffolds / Q000737:chemistry*; D053782:Transforming Growth Factor beta3 / Q000378:metabolism*
chemical_list: C509044:TGFB3 protein, human; D053782:Transforming Growth Factor beta3
keywords: TGF-β; cartilage; chondrogenesis; donor variability; extracellular matrix (ECM); growth factor dosage; stem cells