Traditional treatments for bone injuries have significant limitations. While over one million allogenic and autologous bone grafting procedures are performed each year, significant incidences of medical complications - often involving modest viability, poor integration, or an immune response - still occur. Therefore, the flexibility provided by an in vitro cultured, engineered tissue provides an excellent avenue to repair and replace damaged bone tissue. This approach involves seeding and growing a cell source on a scaffold and implanting the cell-laden construct into the injury site. However, the culture of large volume engineered tissues - and particularly cell viability, expansion, proliferation, and differentiation in these large tissues - is limited by current culture techniques. To address this concern, TR&D1 aims to develop a 3D printed (3DP) bioreactor as a dynamic culture system to control cellular microenvironment and therefore promote cell viability, expansion, proliferation, and differentiation within large engineered constructs. To this end, we have recently developed a tubular perfusion system (TPS) bioreactor that enables the expansion of human mesenchymal stem cells, the differentiation of these cells into osteoblasts, and the subsequent formation of boney tissue. Based on our earlier TPS bioreactor, we will use 3D printing to fabricate specialized bioreactor chambers with variable architecture, controlled flow environments, and spatially located cell populations; thus, we can ensure adequate availability of nutrients and oxygen for the expansion of stem cells within these large constructs. Furthermore, 3D printing control of the spatial location of cell populations will allow us to determine interactions between multiple cell populations, such as mesenchymal stem cells and endothelial cells. Finally, we will utilize the strategies developed in the in vitro 3D bioreactor chambers to fabricate removable, biodegradable scaffolds of engineered bone tissues that are suitable for in vivo application. The results of these studies will deliver a 3DP bioreactor system that can support the growth of large engineered tissues, while also providing a set of tools to develop other, similarly designed, tissue specific bioreactor systems.
Traditional treatments for bone injuries have significant limitations and while bone tissue engineering provides a pathway to overcome these limitations, the culture of large volume engineered tissues are limited by current culture techniques. To address this concern, we aim to develop a 3D printed bioreactor within a dynamic culture system to control the cellular microenvironment so as to promote cell viability, expansion, proliferation, and differentiation within large engineered constructs. The results of these studies will deliver a 3DP bioreactor system that can support the growth of large engineered tissues, while also providing a set of tools to develop other, similarly designed, tissue specific bioreactor systems.
|Patel, Divya B; Luthers, Christopher R; Lerman, Max J et al. (2018) Enhanced extracellular vesicle production and ethanol-mediated vascularization bioactivity via a 3D-printed scaffold-perfusion bioreactor system. Acta Biomater :|
|Kim, Soon Hee; Yeon, Yeung Kyu; Lee, Jung Min et al. (2018) Publisher Correction: Precisely printable and biocompatible silk fibroin bioink for digital light processing 3D printing. Nat Commun 9:2350|
|Bittner, Sean M; Guo, Jason L; Melchiorri, Anthony et al. (2018) Three-dimensional Printing of Multilayered Tissue Engineering Scaffolds. Mater Today (Kidlington) 21:861-874|
|Santoro, Marco; Navarro, Javier; Fisher, John P (2018) Micro- and Macrobioprinting: Current Trends in Tissue Modeling and Organ Fabrication. Small Methods 2:|
|Chim, Letitia K; Mikos, Antonios G (2018) Biomechanical forces in tissue engineered tumor models. Curr Opin Biomed Eng 6:42-50|
|Gao, Teng; Gillispie, Gregory J; Copus, Joshua S et al. (2018) Optimization of gelatin-alginate composite bioink printability using rheological parameters: a systematic approach. Biofabrication 10:034106|
|Tang, Qinggong; Piard, Charlotte; Lin, Jonathan et al. (2018) Imaging stem cell distribution, growth, migration, and differentiation in 3-D scaffolds for bone tissue engineering using mesoscopic fluorescence tomography. Biotechnol Bioeng 115:257-265|
|Smoak, Mollie M; Pearce, Hannah A; Mikos, Antonios G (2018) Microfluidic devices for disease modeling in muscle tissue. Biomaterials :|
|Guo, Ting; Ringel, Julia P; Lim, Casey G et al. (2018) Three dimensional extrusion printing induces polymer molecule alignment and cell organization within engineered cartilage. J Biomed Mater Res A 106:2190-2199|
|Guo, Ting; Noshin, Maeesha; Baker, Hannah B et al. (2018) 3D printed biofunctionalized scaffolds for microfracture repair of cartilage defects. Biomaterials 185:219-231|
Showing the most recent 10 out of 21 publications