Multiphasic microgel-in-gel materials to recapitulate cellular mesoenvironments in vitro

Area of Science:

• Biomaterials Science
• Tissue Engineering
• In Vitro Modeling

Background:

• Living tissues exhibit complex heterogeneity in matrix properties and cellular composition.
• Existing in vitro models often lack the cross-scale complexity to fully recapitulate native tissue environments.
• Accurate recapitulation of tissue complexity is crucial for advancing pathobiology and drug development.

Purpose of the Study:

• To develop a novel class of tunable microgel-in-gel materials for creating advanced multiphasic in vitro models.
• To enable precise control over microenvironmental characteristics by independently tuning microgel and bulk gel properties.
• To demonstrate the utility of these engineered tissue models for studying complex diseases, exemplified by vascularized prostate cancer.

Main Methods:

• Fabrication of multifunctional poly(ethylene glycol)-heparin based microgel-in-gel systems.
• Utilized a novel microfluidic approach for high-throughput production of cell-laden microgels.
• Engineered microgels with adjustable diameters, stiffness, degradability, and biomolecular functionalization.
• Independent selection of microgel and bulk gel structures and compositions for cross-scale control.

Main Results:

• Successfully created tunable microgel-in-gel materials with integrated cell-laden microgels within cell-laden hydrogel matrices.
• Developed a microfluidic method for rapid fabrication of microgels with precisely controlled properties.
• Demonstrated the ability to independently tailor microgel and bulk gel features to achieve designed mesoenvironmental characteristics.
• Constructed a reductionistic in vitro model of vascularized prostate cancer tissue to showcase the platform's potential.

Conclusions:

• The developed microgel-in-gel platform offers unprecedented cross-scale control over in vitro tissue models.
• These advanced models provide enhanced fidelity in mimicking native tissue complexity for biological studies.
• This technology opens new avenues for pathobiology research and accelerates drug development through more predictive testing.