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Customizable, engineered substrates for rapid screening of cellular cues.

Eline Huethorst1, Marie Fa Cutiongco, Fraser A Campbell

  • 1Division of Biomedical Engineering, School of Engineering, University of Glasgow, Glasgow, G12 8LT, United Kingdom. Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, G12 8QQ, United Kingdom.

Biofabrication
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Summary

This study introduces a novel multiwell array platform for high-throughput screening of biophysical cues, accelerating the discovery of cell response mechanisms for biomedical applications.

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Area of Science:

  • Biomaterials Science
  • Cell Biology
  • Tissue Engineering

Background:

  • Biophysical cues significantly influence cell behavior, making them crucial for in vitro and translational biomedical research.
  • Existing high-throughput platforms for studying biophysical cues have limitations in throughput, material diversity, cue segregation, and dynamic response assessment.

Purpose of the Study:

  • To develop and validate a customizable multiwell array platform for high-throughput screening of diverse biophysical cues.
  • To demonstrate the platform's utility in examining the effects of topographical and rigidity cues on cardiomyocyte, chondrocyte, and osteoblast function.

Main Methods:

  • Engineered a multiwell array (3x8) with customizable patterned substrates integrated into a 96-well format.
  • Tested arrays presenting topographical cues (grooves, nanopillars) and rigidity cues (high aspect ratio pillars) to influence specific cell types.
  • Assessed cell responses using live microscopy, quantitative polymerase chain reaction (qPCR), and immunofluorescence.

Main Results:

  • Grooved substrates (5 microm) minimized variations in cardiomyocyte contractile function.
  • Nanopillars (127 nm height, 100 nm diameter, 300 nm pitch) enhanced matrix deposition and chondrogenesis in chondrocytes.
  • High aspect ratio pillars (16 kPa shear modulus) improved osteogenic gene expression in osteoblasts compared to stiff plastic.

Conclusions:

  • The developed multiwell array platform offers enhanced throughput and versatility for systematically screening biophysical cues.
  • This platform facilitates the discovery of specific topographical and rigidity cues that modulate cell function for various biomedical applications.