3D Printed Vascular Networks Enhance Viability in High-Volume Perfusion Bioreactor.
There is a significant clinical need for engineered bone graft substitutes that can quickly, effectively, and safely repair large segmental bone defects. One emerging field of interest involves the growth of engineered bone tissue in vitro within bioreactors, the most promising of which are perfusion bioreactors. Using bioreactor systems, tissue engineered bone constructs can be fabricated in vitro. However, these engineered constructs lack inherent vasculature and once implanted, quickly develop a necrotic core, where no nutrient exchange occurs. Here, we utilized COMSOL modeling to predict oxygen diffusion gradients throughout aggregated alginate constructs, which allowed for the computer-aided design of printable vascular networks, compatible with any large tissue engineered construct cultured in a perfusion bioreactor. We investigated the effect of 3D printed macroscale vascular networks with various porosities on the viability of human mesenchymal stem cells in vitro, using both gas-permeable, and non-gas permeable bioreactor growth chamber walls. Through the use of 3D printed vascular structures in conjunction with a tubular perfusion system bioreactor, cell viability was found to increase by as much as 50% in the core of these constructs, with in silico modeling predicting construct viability at steady state.
Fischell Department of Bioengineering, University of Maryland, 2330D Jeong H. Kim Engineering Building, College Park, MD, 20742, USA.
Owen
O
Ball
Fischell Department of Bioengineering, University of Maryland, 2330D Jeong H. Kim Engineering Building, College Park, MD, 20742, USA.
Bao-Ngoc B
BB
Nguyen
Fischell Department of Bioengineering, University of Maryland, 2330D Jeong H. Kim Engineering Building, College Park, MD, 20742, USA.
Jesse K
JK
Placone
Fischell Department of Bioengineering, University of Maryland, 2330D Jeong H. Kim Engineering Building, College Park, MD, 20742, USA. jpfisher@umd.edu.
John P
JP
Fisher
D019149:Bioreactors; D001808:Blood Vessels; D018786:Bone Substitutes / Q000737:chemistry*; D002470:Cell Survival; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D066330:Printing, Three-Dimensional; D023822:Tissue Engineering / Q000379:methods*
D018786:Bone Substitutes
3D printed; Bioreactor; Computer-aided design; Modeling; Perfusion; Vascular; hMSCs