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3D Bio-printing Of Living Structures With Built-In Chemical Sensors.

COPENHAGEN, Denmark, October 1, 2018 -- European scientists have developed a technology that enables non-invasive monitoring of oxygen metabolism in cells that are 3D-bio-printed into complex living structures.

This has implications for studies of cell growth and interactions e.g. under tissue-like conditions, as well as for the design of 3D printed constructs facilitating higher productivity of microalgae in biofilms or better oxygen supply for stem cells used in bone and tissue reconstruction efforts.

The international team of researchers led by Michael Kuhl of the University of Copenhagen used oxygen sensitive nanoparticles to make a gel material that can be used for 3D printing of complex, biofilm and tissue like structures harboring living cells as well as built-in chemical sensors.

3D printing is a widespread technique for producing object in plastic, metal, and other abiotic materials.

Living cells can be 3D printed in biocompatible gel materials (bio-inks) and such 3D bio-printing is a rapidly developing field, e.g., in biomedical studies, where stem cells are cultivated in 3D printed constructs mimicking the complex structure of tissue and bones.

Such attempts lack on line monitoring of the metabolic activity of cells growing in bio-printed constructs, though the measurements largely rely on destructive sampling.

"We have developed a patent pending solution to this problem," Kuhl said.

The group developed a functionalized bio-ink by implementing luminescent oxygen sensitive nanoparticles into the print matrix.

When blue light excites the nanoparticles, they emit red luminescent light in proportion to the local oxygen concentration--the more oxygen the less red luminescence.

The distribution of red luminescence and thus oxygen across bio-printed living structures can be imaged with a camera system.

This allows for on-line, non-invasive monitoring of oxygen distribution and dynamics that can be mapped to the growth and distribution of cells in the 3D bio-printed constructs without the need for destructive sampling.

The addition of nanoparticles doesn't change the mechanical properties of the bio-ink, e.g., to avoid cell stress and death during the printing process.

Furthermore, the nanoparticles do not inhibit or interfere with the cells. The method shows good biocompatibility and can be used with microalgae as well as sensitive human cell lines.

The study demonstrates how bio-inks functionalized with sensor nanoparticles can be calibrated and used, for example for monitoring algal photosynthesis and respiration as well as stem cell respiration in bioprinted structures with one or several cell types.

The breakthrough in 3D bio-printing makes it possible to monitor the oxygen metabolism and micro-environment of cells on line, and non-invasively in intact 3D printed living structures.

A key challenge in growing stem cells in larger tissue- or bone-like structures is to ensure a sufficient oxygen supply for the cells. The new method makes it possible to visualize the oxygen conditions in 3D bioprinted structures, which, e.g., enables rapid testing and optimization of stem cell growth in differently designed constructs.

The team is very interested in exploring new collaborations and applications of their developments.

3D bio-printing with functionalized bio-inks can be applied in many other research fields than biomedicine.

"It is extremely inspiring to combine such advanced materials science and sensor technology with my research in microbiology and biophotonics, where we now employ 3D bio-printing to study microbial interactions and photobiology," Kuhl said.

Researchers at the Technical University of Dresden participated in the study.

Citation: Erik Trampe et al., Functionalized Bio-ink with Optical Sensor Nanoparticles for O2 Imaging in 3D-Bio-printed Constructs. Advanced Functional Materials, 2018; 1804411 DOI: 10.1002/adfm.201804411


Contact: Michael Kuhl,
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Publication:Stem Cell Research News
Date:Oct 8, 2018
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