title: Controlled release of transforming growth factor-β3 from cartilage-extra-cellular-matrix-derived scaffolds to promote chondrogenesis of human-joint-tissue-derived stem cells.
abstract: 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.
authors.affiliation: Trinity Centre for Bioengineering, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland; Department of Mechanical and Manufacturing Engineering, School of Engineering, Trinity College Dublin, Dublin 2, Ireland.
authors.forename: Henrique V
authors.initials: HV
authors.lastname: Almeida
authors.affiliation: Trinity Centre for Bioengineering, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland; Department of Mechanical and Manufacturing Engineering, School of Engineering, Trinity College Dublin, Dublin 2, Ireland.
authors.forename: Yurong
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Trinity Centre for Bioengineering, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland; Department of Mechanical and Manufacturing Engineering, School of Engineering, Trinity College Dublin, Dublin 2, Ireland.
authors.forename: Gráinne M
authors.initials: GM
authors.lastname: Cunniffe
authors.affiliation: Sports Surgery Clinic, Santry, Dublin 9, 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 2, Ireland; Tissue Engineering Research Group, Department of Anatomy, Royal College of Surgeons in Ireland, Dublin 2, Ireland; Advanced Materials and Bioengineering Research Centre (AMBER), Trinity College Dublin & RCSI, Dublin 2, Ireland.
authors.forename: Amos
authors.initials: A
authors.lastname: Matsiko
authors.affiliation: Trinity Centre for Bioengineering, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland; Department of Mechanical and Manufacturing Engineering, School of Engineering, Trinity College Dublin, Dublin 2, Ireland.
authors.forename: Conor T
authors.initials: CT
authors.lastname: Buckley
authors.affiliation: Trinity Centre for Bioengineering, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland; Tissue Engineering Research Group, Department of Anatomy, Royal College of Surgeons in Ireland, Dublin 2, Ireland; Advanced Materials and Bioengineering Research Centre (AMBER), Trinity College Dublin & RCSI, Dublin 2, 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 2, Ireland; Department of Mechanical and Manufacturing Engineering, School of Engineering, Trinity College Dublin, Dublin 2, Ireland; Advanced Materials and Bioengineering Research Centre (AMBER), Trinity College Dublin & RCSI, Dublin 2, Ireland. Electronic address: kellyd9@tcd.ie.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Kelly
mesh_terms: D040761:Biomimetic Materials / Q000737:chemistry / Q000494:pharmacology; D002358:Cartilage, Articular / Q000166:cytology / Q000378:metabolism; D020219:Chondrogenesis / Q000187:drug effects*; D003692:Delayed-Action Preparations / Q000737:chemistry / Q000494:pharmacology; D005109:Extracellular Matrix / Q000737:chemistry*; D005260:Female; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry / Q000494:pharmacology; D007596:Joints / Q000166:cytology / Q000378:metabolism*; D008297:Male; D012038:Regeneration / Q000187:drug effects; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D054457:Tissue Scaffolds / Q000737:chemistry*; D053782:Transforming Growth Factor beta3 / Q000737:chemistry / Q000494:pharmacology
chemical_list: D003692:Delayed-Action Preparations; C509044:TGFB3 protein, human; D053782:Transforming Growth Factor beta3; D006820:Hyaluronic Acid
keywords: Articular cartilage; Crosslinking; Extracellular matrix; Stem cells; Tissue engineering