title: Altering the architecture of tissue engineered hypertrophic cartilaginous grafts facilitates vascularisation and accelerates mineralisation.
abstract: Cartilaginous tissues engineered using mesenchymal stem cells (MSCs) can be leveraged to generate bone in vivo by executing an endochondral program, leading to increased interest in the use of such hypertrophic grafts for the regeneration of osseous defects. During normal skeletogenesis, canals within the developing hypertrophic cartilage play a key role in facilitating endochondral ossification. Inspired by this developmental feature, the objective of this study was to promote endochondral ossification of an engineered cartilaginous construct through modification of scaffold architecture. Our hypothesis was that the introduction of channels into MSC-seeded hydrogels would firstly facilitate the in vitro development of scaled-up hypertrophic cartilaginous tissues, and secondly would accelerate vascularisation and mineralisation of the graft in vivo. MSCs were encapsulated into hydrogels containing either an array of micro-channels, or into non-channelled 'solid' controls, and maintained in culture conditions known to promote a hypertrophic cartilaginous phenotype. Solid constructs accumulated significantly more sGAG and collagen in vitro, while channelled constructs accumulated significantly more calcium. In vivo, the channels acted as conduits for vascularisation and accelerated mineralisation of the engineered graft. Cartilaginous tissue within the channels underwent endochondral ossification, producing lamellar bone surrounding a hematopoietic marrow component. This study highlights the potential of utilising engineering methodologies, inspired by developmental skeletal processes, in order to enhance endochondral bone regeneration strategies.
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: Eamon J
authors.initials: EJ
authors.lastname: Sheehy
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; School of Agriculture and Food Science, University College Dublin, Belfield, Dublin, Ireland.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Vinardell
authors.affiliation: Department of Pathology, School of Dental Science, Trinity College Dublin, Dublin, Ireland.
authors.forename: Mary E
authors.initials: ME
authors.lastname: Toner
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; Advanced Materials and Bioengineering Research Centre (AMBER), Trinity College Dublin, Dublin, Ireland.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Kelly
mesh_terms: D000818:Animals; D002113:Calcification, Physiologic; D002118:Calcium / Q000378:metabolism; D002356:Cartilage / Q000098:blood supply / Q000166:cytology* / Q000502:physiology; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology; D020219:Chondrogenesis; D020100:Hydrogels / Q000737:chemistry; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010012:Osteogenesis; D013552:Swine; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D020100:Hydrogels; D002118:Calcium