Tuning the Morphological Properties of Granular Hydrogels to Control Lymphatic Capillary Formation

Area of Science:

• Biomaterials Science
• Tissue Engineering
• Regenerative Medicine

Background:

• Granular hydrogels mimic the extracellular matrix, supporting tissue regeneration.
• Controlling hydrogel properties is crucial for guiding cellular behavior and tissue development.

Purpose of the Study:

• To investigate how granular hydrogel properties, specifically morphology and packing, affect lymphatic tube formation.
• To determine the key factors governing lymphatic capillary development within engineered hydrogels.

Main Methods:

• Fabrication of norbornene-modified hyaluronic acid (NorHA) microgels using pipetting or vortexing.
• Assembly of microgels into granular hydrogels under loose and tight packing conditions.
• Analysis of gel morphology, rheological properties, and lymphatic capillary formation via gene and protein expression.

Main Results:

• Lymphatic capillary formation was observed exclusively in tightly packed granular hydrogels.
• Gel morphology (pore size and topology) was more critical for lymphatic formation than bulk stiffness.
• Vortexed (V180s) gels showed earlier lymphatic gene and protein expression, while pipetted gels exhibited enhanced capillary connectivity and linearity.

Conclusions:

• Lymphatic tube formation in granular hydrogels is primarily governed by pore size and gel topology, not mechanical stiffness.
• Optimizing granular hydrogel morphology is essential for advancing lymphatic tissue engineering strategies.
• These findings provide insights for designing biomaterials to promote lymphatic regeneration.