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Sacrificial capillary pumps to engineer multiscalar biological forms.

Subramanian Sundaram1,2,3, Joshua H Lee4,5, Isabel M Bjørge4,5,6

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Engineered sacrificial capillary pumps (ESCAPE) enable multiscalar tissue fabrication in hydrogels, creating complex vascular structures from microvasculature to millimeter scales previously inaccessible.

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Area of Science:

  • Biomaterials Science
  • Tissue Engineering
  • Regenerative Medicine

Background:

  • Natural tissues exhibit complex multiscalar architectures regulating biological functions.
  • Current bioprinting and photoablation methods face limitations in achieving both large-scale constructs and subcellular resolution.
  • Fabricating multiscalar biological motifs, like vascular trees, in soft hydrogels remains a significant challenge.

Purpose of the Study:

  • To develop a novel method for fabricating multiscalar structures in soft natural hydrogels.
  • To overcome the limitations of existing additive and subtractive biomanufacturing techniques.
  • To enable the creation of complex tissue architectures, including vascular networks, with high fidelity across multiple length scales.

Main Methods:

  • Utilized gallium-based engineered sacrificial capillary pumps for evacuation (ESCAPE) during moulding.
  • Decoupled biomaterial choice from geometric construction process.
  • Employed non-biocompatible tools for initial geometry creation within soft hydrogels.

Main Results:

  • Successfully generated multiscalar structures in soft natural hydrogels, achieving cellular-scale (<10 µm) and millimeter-scale features.
  • Fabricated branched, cell-laden vascular trees in collagen, with diameters ranging from 300-µm arterioles down to microvasculature.
  • Demonstrated micropatterning of vascular wall inner surfaces with topographical cues for cell orientation and engineering of fine structures like vascular malformations.

Conclusions:

  • ESCAPE moulding provides a versatile platform for fabricating complex multiscalar forms in soft biomaterials.
  • This technique overcomes previous technological barriers in tissue engineering, enabling previously inaccessible in vitro tissue architectures.
  • Paves the way for advanced tissue models and regenerative medicine applications requiring intricate, multiscalar designs.