Engineering towards functional tissues and organs

Jayasinghe, Suwan N.

doi:10.4161/org.6.3.12901

Cited by 4 publications

(1 citation statement)

References 14 publications

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“…In mammals, this is achieved by air mixing with the blood in the lungs and then being distributed to tissues by means of the vasculature (vascular perfusion). However, improper or poor provision of oxygen to cells within the tissue bulk severely limits the ability of many bioreactors to support tissue culture [5][6][7][8]17,19,20 so that all cells receive proper metabolic and stimulatory support. Compared to cells cultured in 2 dimensions, engineered tissues with 3D structures, biofabricated by means of bioprinting or other methods, can plausibly be tuned to meet specific genetic, cellular, structural, extracellular, and metabolic parameters, and thus have incredible potential to provide tissues for clinical implants, research models, and drug testing platforms.…”

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confidence: 99%

Oxygenation Profiles of Human Blood, Cell Culture Medium, and Water for Perfusion of 3D-Bioprinted Tissues using the FABRICA Bioreactor Platform

Chen

Lashmet

Isidan

et al. 2020

Sci Rep

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Persistent and saturated oxygen distribution from perfusion media (i.e., blood, or cell culture media) to cells within cell-dense, metabolically-active biofabricated tissues is required to keep them viable. Improper or poor oxygen supply to cells within the tissue bulk severely limits the tissue culturing potential of many bioreactors. We added an oxygenator module to our modular FABRICA bioreactor in order to provide stable oxygenation to biofabricated tissues during culture. In this proof of concept study of an oxygenated and perfused bioreactor, we characterized the oxygenation of water, cell culture medium, and human blood in the FABRICA as functions of augmenting vacuum (air inlet) pressure, perfusion (volumetric flow) rate, and tubing/oxygenator components. The mean oxygen levels for water and cell culture media were 27.7 ± 2.1% and 27.6 ± 4.1%, respectively. The mean oxygen level for human blood was 197.0 ± 90.0 mmHg, with near-physiologic levels achieved with low-permeability PharMed tubing alone (128.0 ± 14.0 mmHg). Hematologic values pre-and post-oxygenation, respectively were (median ± IQR): Red blood cell: 6.0 ± 0.5 (10 6 /μL) and 6.5 ± 0.4 (10 6 /μL); Hemoglobin: 17.5 ± 1.2 g/dL and 19.2 ± 3.0 g/dL; and Hematocrit: 56.7 ± 2.4% and 61.4 ± 7.5%. The relative stability of the hematologic parameters indicates that blood function and thus blood cell integrity were maintained throughout oxygenation. Already a versatile research tool, the now oxygenated FABRICA provides easy-to-implement, in vivo-like perfusion and stable oxygenation culture conditions in vitro semi-independently of one another, which means the bioreactor has the potential to serve as a platform for investigating the behavior of 3D tissue models (regardless of biofabrication method), performing drug toxicity-testing, and testing pharmaceutical efficacy/safety. Recent 3D bioprinting/biofabrication advances allow generation of scaffold-free engineered tissue constructs with customizable 3D design and high cell density 1-4. These engineered tissues are comprised of cells in contact with one another and with extracellular matrix (ECM) in dense 3D structures, thus making them similar to natural tissues in vivo with the same requirements of controlled, well-distributed oxygenation, nutrition, mechanical (shear, compressive, and tensile) forces, temperature, pH, etc. 5-15 so that all cells receive proper metabolic and stimulatory support. Compared to cells cultured in 2 dimensions, engineered tissues with 3D structures, biofabricated by means of bioprinting or other methods, can plausibly be tuned to meet specific genetic, cellular, structural, extracellular, and metabolic parameters, and thus have incredible potential to provide tissues for clinical implants, research models, and drug testing platforms. Importantly, given that media (cell culture media or blood), used to perfuse biofabricated tissue cultured in bioreactors, is one constituent providing multiple critical metabolic factors (convective heat, nutrients, shear stress, and oxygen), the...

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confidence: 99%