SABER bioprinting: a temporal platform for multiday assembly of engineered tissues

Area of Science:

• Biomaterials Science
• Tissue Engineering
• Regenerative Medicine

Background:

• Current bioprinting methods are limited to single fabrication sessions, restricting construct scale, complexity, and maturation.
• Achieving larger, more complex, and biologically mature engineered tissues requires overcoming these temporal limitations.

Purpose of the Study:

• To introduce and validate Sequential Additive Biofabrication Extended over Real-time (SABER), a novel bioprinting strategy.
• To demonstrate multi-day fabrication of soft-hydrogel constructs with continuous perfusion culture, incorporating time as a design variable.

Main Methods:

• Developed SABER, integrating a thermoresponsive methylcellulose-agarose support with a custom perfusion bioreactor.
• Enabled high-fidelity collagen deposition at low temperatures and mechanical stabilization at culture temperatures.
• Facilitated direct through-tissue perfusion for thick constructs.

Main Results:

• Successfully fabricated layered constructs, nested geometries, and suspended internal features over multiple days.
• Demonstrated scalability with a 10-layer, ~1 cm thick construct, exceeding single-session limits.
• Achieved viability and contractility of printed cardiac tissues after one week of perfusion culture, with in situ differentiation of iPS cells.

Conclusions:

• SABER is a proof-of-concept platform for time-resolved, perfused bioprinting of soft hydrogel constructs.
• This approach introduces time as an explicit design variable, enabling fabrication workflows beyond current single-session capabilities.
• Provides a foundation for future advancements in large-scale, temporally complex biofabrication.