Dynamic Bioreactors with Integrated Microfabricated Devices for Mechanobiological Screening

Area of Science:

• Tissue Engineering
• Biomaterials Science
• Mechanobiology

Background:

• Biomechanical stimulation is crucial for engineered tissue development but optimizing protocols is challenging due to multifactorial microenvironmental influences.
• Traditional bioreactors lack the throughput for combinatorial testing, while microfabricated systems often compromise uniformity and robustness.

Purpose of the Study:

• To develop a high-throughput platform for combinatorial testing of mechanobiological parameters in engineered tissues.
• To enable systematic investigation of cell responses to combined mechanical stimuli, biomaterial properties, and biochemical factors.

Main Methods:

• A hybrid approach using microfabricated polydimethylsiloxane (PDMS) inserts within a standard dynamic bioreactor.
• Each insert accommodates 35 cell-seeded microscale hydrogels, allowing simultaneous cyclic tensile strain application.
• Up to eight inserts can be used concurrently, enabling testing of up to 280 microtissues per experiment.

Main Results:

• Uniformity of applied tensile strains across microtissues was experimentally validated.
• Proof-of-principle experiments revealed combinatorial effects of dynamic strain, stiffness, and TGF-β1 on myofibroblast differentiation.
• Identified both known and novel interaction effects, informing tissue engineering strategies.

Conclusions:

• The developed platform significantly enhances throughput for mechanobiological studies in tissue engineering.
• This system provides a robust and versatile tool for systematically probing combinations of parameters to optimize cell fate and engineered tissue function.
• The platform has broad applicability for advancing the field of tissue engineering and regenerative medicine.