Stress-Adaptive Biomaterials With Tunable Yielding Architectures Regulate Organoid Morphogenesis

Area of Science:

• Biomaterials Science
• Tissue Engineering
• Biophysics

Background:

• The yield stress of biomaterials, a critical factor in plastic deformation, limits stress development in growing encapsulated tissues.
• While matrix stiffness and viscoelasticity are known to influence cells, the specific role of yield stress has been difficult to ascertain.

Purpose of the Study:

• To engineer a granular hydrogel platform enabling precise, quantitative tuning of biomaterial yield stress.
• To investigate the impact of tunable yield stress on cellular behaviors, including cancer cell migration and neural organoid development.

Main Methods:

• Development of a granular hydrogel using supramolecular host-guest dynamic crosslinkers for tunable yield stress.
• Quantitative measurement and adjustment of matrix yield stress between 12 and 370 Pa, with storage modulus below ~0.1 kPa.
• Application of the hydrogel platform to model non-adhesive cancer migration and early-stage midbrain organoid development.

Main Results:

• The tunable yield stress range was found to effectively promote or inhibit peripheral shedding in a cancer migration model.
• Early development of midbrain organoids demonstrated exquisite sensitivity to matrix yield stress, with specific values influencing neural rosette formation.
• Yield stresses as low as 25 Pa significantly promoted bud-like protrusions and neural rosettes, while 10 Pa variations limited these developmental phenotypes.

Conclusions:

• Biomaterial yield stress is a critical mechanical parameter that can be precisely controlled to influence tissue morphogenesis and organization.
• This tunable yield stress platform offers a novel approach for designing biomaterials for advanced disease modeling and regenerative medicine applications.