title: Engineering zonal cartilaginous tissue by modulating oxygen levels and mechanical cues through the depth of infrapatellar fat pad stem cell laden hydrogels.
abstract: Engineering tissues with a structure and spatial composition mimicking those of native articular cartilage (AC) remains a challenge. This study examined if infrapatellar fat pad-derived stem cells (FPSCs) can be used to engineer cartilage grafts with a bulk composition and a spatial distribution of matrix similar to the native tissue. In an attempt to mimic the oxygen gradients and mechanical environment within AC, FPSC-laden hydrogels (either 2 mm or 4 mm in height) were confined to half of their thickness and/or subjected to dynamic compression (DC). Confining FPSC-laden hydrogels was predicted to accentuate the gradient in oxygen tension through the depth of the constructs (higher in the top and lower in the bottom), leading to enhanced glycosaminoglycan (GAG) and collagen synthesis in 2 mm high tissues. When subjected to DC alone, both GAG and collagen accumulation increased within 2 mm high unconfined constructs. Furthermore, the dynamic modulus of constructs increased from 0.96 MPa to 1.45 MPa following the application of DC. There was no synergistic benefit of coupling confinement and DC on overall levels of matrix accumulation; however in all constructs, irrespective of their height, the combination of these boundary conditions led to the development of engineered tissues that spatially best resembled native AC. The superficial region of these constructs mimicked that of native tissue, staining weakly for GAG, strongly for type II collagen, and in 4 mm high tissues more intensely for proteoglycan 4 (lubricin). This study demonstrated that FPSCs respond to joint-like environmental conditions by producing cartilage tissues mimicking native AC. 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: Lu
authors.initials: L
authors.lastname: Luo
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: Adam R
authors.initials: AR
authors.lastname: O'Reilly
authors.affiliation: Institute of Bioengineering, School of Engineering and Materials Science, Queen Mary University of London, London, UK.
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Thorpe
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: Conor T
authors.initials: CT
authors.lastname: Buckley
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.|Department of Anatomy, Royal College of Surgeons in Ireland, Dublin, Ireland.|Advanced Materials and Bioengineering Research Centre (AMBER), Royal College of Surgeons in Ireland and Trinity College Dublin, Dublin, Ireland.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Kelly
mesh_terms: D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D002356:Cartilage / Q000166:cytology / Q000378:metabolism*; D019245:Compressive Strength; D020100:Hydrogels / Q000737:chemistry / Q000494:pharmacology; D010100:Oxygen / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D013314:Stress, Mechanical; D013552:Swine; D023822:Tissue Engineering
chemical_list: D020100:Hydrogels; D010100:Oxygen
keywords: cartilage tissue engineering; confinement; dynamic compression; mechanical environment; oxygen; proteoglycan 4