Mechanical Mapping of Bioprinted Hydrogel Models by Brillouin Microscopy

Three-dimensional (3D) bioprinting has revolutionised the field of biofabrication by delivering precise, cost-effective and a relatively simple way of engineering in vitro living systems in high volume for use in tissue regeneration, biological modelling, drug testing and cell-based diagnostics. The complexity of modern bioprinted systems requires quality control assessment to ensure the resulting product meets the desired criteria of structural design, micromechanical performance and long-term durability. Brillouin microscopy could be an excellent solution for micromechanical assessment of the bioprinted models during or post-fabrication since this technology is non-destructive, label-free and is capable of microscale 3D imaging. In this work, we demonstrate the application of Brillouin microscopy to 3D imaging of hydrogel microstructures created through drop-on-demand bioprinting. In addition, we show that this technology can resolve variations between mechanical properties of the gels with slightly different polymer fractions. This work confirms that Brillouin microscopy can be seen as a characterisation technology complementary to bioprinting, and in the future can be combined within the printer design to achieve simultaneous real-time fabrication and micromechanical characterisation of in vitro biological systems.

[1]  H. Clausen‐Schaumann,et al.  Precision 3D‐Printed Cell Scaffolds Mimicking Native Tissue Composition and Mechanics , 2020, Advanced healthcare materials.

[2]  C. P. Winlove,et al.  Viscoelastic properties of biopolymer hydrogels determined by Brillouin spectroscopy: A probe of tissue micromechanics , 2020, Science Advances.

[3]  Liliang Ouyang,et al.  Expanding and optimizing 3D bioprinting capabilities using complementary network bioinks , 2020, Science Advances.

[4]  H. Ramon,et al.  The Influence of Swelling on Elastic Properties of Polyacrylamide Hydrogels , 2020, Frontiers in Materials.

[5]  A. Gaipov,et al.  Development and validation of hybrid Brillouin-Raman spectroscopy for non-contact assessment of mechano-chemical properties of urine proteins as biomarkers of kidney diseases , 2020, BMC Nephrology.

[6]  R. Prevedel,et al.  Recent progress and current opinions in Brillouin microscopy for life science applications , 2020, Biophysical Reviews.

[7]  Yingying Wang,et al.  Background-free fibre optic Brillouin probe for remote mapping of micromechanics. , 2020, Biomedical optics express.

[8]  Ibrahim T. Ozbolat,et al.  The bioprinting roadmap , 2020, Biofabrication.

[9]  I. Kabakova,et al.  Brillouin imaging for studies of micromechanics in biology and biomedicine: from current state-of-the-art to future clinical translation , 2020, Journal of Physics: Photonics.

[10]  C. P. Winlove,et al.  Brillouin-derived viscoelastic parameters of hydrogel tissue models , 2019, 1912.08292.

[11]  Robert Prevedel,et al.  Brillouin microscopy: an emerging tool for mechanobiology , 2019, Nature Methods.

[12]  Damien Loterie,et al.  Volumetric Bioprinting of Complex Living‐Tissue Constructs within Seconds , 2019, Advanced materials.

[13]  Gi Hoon Yang,et al.  4D Bioprinting: Technological Advances in Biofabrication. , 2019, Macromolecular bioscience.

[14]  A. Torricelli,et al.  Accuracy and precision of tissue optical properties and hemodynamic parameters estimated by the BabyLux device: a hybrid time-resolved near-infrared and diffuse correlation spectroscopy neuro-monitor. , 2019, Biomedical optics express.

[15]  Jianzhong Fu,et al.  3D printing of complex GelMA-based scaffolds with nanoclay , 2019, Biofabrication.

[16]  M. Badea,et al.  Influence of Matrigel on Single- and Multiple-Spheroid Cultures in Breast Cancer Research , 2019, SLAS discovery : advancing life sciences R & D.

[17]  D. Fioretto,et al.  Brillouin-Raman mapping of natural fibers with spectral moment analysis , 2019, Biomedical optics express.

[18]  Daniele Fioretto,et al.  Brillouin Light Scattering: Applications in Biomedical Sciences , 2019, Chemical reviews.

[19]  Alice Berthelot,et al.  High-Frequency Mechanical Properties of Tumors Measured by Brillouin Light Scattering. , 2019, Physical review letters.

[20]  Malcolm Xing,et al.  3D bioprinting for biomedical devices and tissue engineering: A review of recent trends and advances , 2018, Bioactive materials.

[21]  Thomas Bley,et al.  Additive Biotech-Chances, challenges, and recent applications of additive manufacturing technologies in biotechnology. , 2017, New biotechnology.

[22]  Amir Sanati-Nezhad,et al.  Manufacturing of hydrogel biomaterials with controlled mechanical properties for tissue engineering applications. , 2017, Acta biomaterialia.

[23]  Vladimir Mironov,et al.  Bioprinting of a functional vascularized mouse thyroid gland construct , 2017, Biofabrication.

[24]  Zhaokai Meng,et al.  Assessment of Local Heterogeneity in Mechanical Properties of Nanostructured Hydrogel Networks. , 2017, ACS nano.

[25]  Alexandra L Rutz,et al.  A bioprosthetic ovary created using 3D printed microporous scaffolds restores ovarian function in sterilized mice , 2017, Nature Communications.

[26]  Wai Yee Yeong,et al.  Investigation of cell viability and morphology in 3D bio-printed alginate constructs with tunable stiffness. , 2017, Journal of biomedical materials research. Part A.

[27]  S. Speziale,et al.  Single-crystal elasticity of SrCO3 by Brillouin spectroscopy , 2017 .

[28]  Qian Wang,et al.  Influence of Surface Topographical Cues on the Differentiation of Mesenchymal Stem Cells in Vitro. , 2016, ACS biomaterials science & engineering.

[29]  A. J. Putnam,et al.  Extracellular matrix elasticity and topography: material-based cues that affect cell function via conserved mechanisms. , 2015, Journal of biomedical materials research. Part A.

[30]  A. Wan,et al.  Modulation of chondrocyte functions and stiffness-dependent cartilage repair using an injectable enzymatically crosslinked hydrogel with tunable mechanical properties. , 2014, Biomaterials.

[31]  Kristi S. Anseth,et al.  Mechanical Properties and Degradation of Chain and Step-Polymerized Photodegradable Hydrogels , 2013, Macromolecules.

[32]  A. Engler,et al.  Preparation of Hydrogel Substrates with Tunable Mechanical Properties , 2010, Current protocols in cell biology.

[33]  C. Murphy,et al.  The elastic modulus of Matrigel as determined by atomic force microscopy. , 2009, Journal of structural biology.

[34]  Chien-Chih Chen,et al.  Letters. Elasticity of single-crystal calcite and rhodochrosite by Brillouin spectroscopy , 2001 .

[35]  G. Scarcelli,et al.  Noninvasive Imaging: Brillouin Confocal Microscopy. , 2018, Advances in experimental medicine and biology.

[36]  Dujing Wang,et al.  Mechanical properties of PNIPAM based hydrogels: A review. , 2017, Materials science & engineering. C, Materials for biological applications.

[37]  S. Yun,et al.  Confocal Brillouin microscopy for three-dimensional mechanical imaging. , 2007, Nature photonics.

[38]  Supplementary Note 1: Longitudinal Modulus , 2022 .