<p>Complex and robust tissue self-organization requires defined initial conditions and dynamic boundaries—neighbouring tissues and extracellular matrix that actively evolve to guide morphogenesis. A major challenge in tissue engineering is identifying material properties that are compatible with controlling initial culture conditions while mimicking dynamic tissue boundaries. Here we describe a highly tunable granular biomaterial, MAGIC matrix, that supports both long-term bioprinting and gold-standard tissue self-organization. We identify that significant stress relaxation at the long timescales and large deformation magnitudes relevant to self-organization is required for optimal morphogenesis. We apply optimized MAGIC matrices toward precise extrusion bioprinting of saturated cell suspensions directly into three-dimensional culture. Carefully controlling initial conditions for tissue growth yields dramatic increases in organoid reproducibility and complexity across multiple tissue types, enabling high-throughput generation of organoid arrays and perfusable three-dimensional microphysiological systems. Our results identify key biomaterial parameters for optimal organoid morphogenesis and lay the foundation for fabricating more complex and reproducible self-organized tissues.</p>

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Stress-relaxing granular bioprinting materials enable complex and uniform organoid self-organization

  • Austin J. Graham,
  • Michelle W. L. Khoo,
  • Vasudha Srivastava,
  • Sara Viragova,
  • Honesty Kim,
  • Kavita Parekh,
  • Kelsey M. Hennick,
  • Malia Bird,
  • Nadine Goldhammer,
  • Jie Zeng Yu,
  • Grace Hu,
  • Natasha T. Brinkley,
  • Lucas Pardo,
  • Jasmine S. Amaya,
  • Cameron D. Morley,
  • Nishant Chadha,
  • Paul Lebel,
  • Sanjay Kumar,
  • Jennifer M. Rosenbluth,
  • Tomasz J. Nowakowski,
  • Ovijit Chaudhuri,
  • Ophir Klein,
  • Rafael Gómez-Sjöberg,
  • Zev J. Gartner

摘要

Complex and robust tissue self-organization requires defined initial conditions and dynamic boundaries—neighbouring tissues and extracellular matrix that actively evolve to guide morphogenesis. A major challenge in tissue engineering is identifying material properties that are compatible with controlling initial culture conditions while mimicking dynamic tissue boundaries. Here we describe a highly tunable granular biomaterial, MAGIC matrix, that supports both long-term bioprinting and gold-standard tissue self-organization. We identify that significant stress relaxation at the long timescales and large deformation magnitudes relevant to self-organization is required for optimal morphogenesis. We apply optimized MAGIC matrices toward precise extrusion bioprinting of saturated cell suspensions directly into three-dimensional culture. Carefully controlling initial conditions for tissue growth yields dramatic increases in organoid reproducibility and complexity across multiple tissue types, enabling high-throughput generation of organoid arrays and perfusable three-dimensional microphysiological systems. Our results identify key biomaterial parameters for optimal organoid morphogenesis and lay the foundation for fabricating more complex and reproducible self-organized tissues.