3D Bioprinting of Developmentally Inspired Templates for Whole Bone Organ Engineering.
The ability to print defined patterns of cells and extracellular-matrix components in three dimensions has enabled the engineering of simple biological tissues; however, bioprinting functional solid organs is beyond the capabilities of current biofabrication technologies. An alternative approach would be to bioprint the developmental precursor to an adult organ, using this engineered rudiment as a template for subsequent organogenesis in vivo. This study demonstrates that developmentally inspired hypertrophic cartilage templates can be engineered in vitro using stem cells within a supporting gamma-irradiated alginate bioink incorporating Arg-Gly-Asp adhesion peptides. Furthermore, these soft tissue templates can be reinforced with a network of printed polycaprolactone fibers, resulting in a ≈350 fold increase in construct compressive modulus providing the necessary stiffness to implant such immature cartilaginous rudiments into load bearing locations. As a proof-of-principal, multiple-tool biofabrication is used to engineer a mechanically reinforced cartilaginous template mimicking the geometry of a vertebral body, which in vivo supported the development of a vascularized bone organ containing trabecular-like endochondral bone with a supporting marrow structure. Such developmental engineering approaches could be applied to the biofabrication of other solid organs by bioprinting precursors that have the capacity to mature into their adult counterparts over time in vivo.
Trinity Centre for Bioengineering and Department of Mechanical and Manufacturing Engineering, Trinity College Dublin, The University of Dublin, Dublin 2, Ireland.
Andrew C
AC
Daly
Trinity Centre for Bioengineering and Department of Mechanical and Manufacturing Engineering, Trinity College Dublin, The University of Dublin, Dublin 2, Ireland.
Gráinne M
GM
Cunniffe
Trinity Centre for Bioengineering and Department of Mechanical and Manufacturing Engineering, Trinity College Dublin, The University of Dublin, Dublin 2, Ireland.
Binulal N
BN
Sathy
Departments of Biomedical Engineering and Orthopedic Surgery, and the National Centre for Regenerative Medicine, Case Western Reserve University, Cleveland, OH, USA.
Oju
O
Jeon
Departments of Biomedical Engineering and Orthopedic Surgery, and the National Centre for Regenerative Medicine, Case Western Reserve University, Cleveland, OH, USA.
Eben
E
Alsberg
Trinity Centre for Bioengineering and Department of Mechanical and Manufacturing Engineering, Trinity College Dublin, The University of Dublin, Dublin 2, Ireland. kellyd9@tcd.ie.
Daniel J
DJ
Kelly
D000464:Alginates / Q000737:chemistry*; D000818:Animals; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009842:Oligopeptides / Q000737:chemistry*; D011091:Polyesters / Q000737:chemistry*; D066330:Printing, Three-Dimensional; D013131:Spine; D013552:Swine; D023822:Tissue Engineering
D000464:Alginates; D006603:Hexuronic Acids; D009842:Oligopeptides; D011091:Polyesters; C016240:polycaprolactone; C047981:arginyl-glycyl-aspartic acid; D020723:Glucuronic Acid
3D bioprinting; bone organ; endochondral ossification; organ engineering