Simple Preparation of Injectable Hydrogels with Phase-Separated Structures That Can Encapsulate Live Cells

Area of Science:

• Biomaterials Science
• Tissue Engineering
• Polymer Chemistry

Background:

• Injectable hydrogels are promising for minimally invasive delivery as artificial extracellular matrix (ECM) materials.
• Conventional hydrogels lack phase-separated structures found in natural ECMs, limiting their biomimicry.
• Natural ECMs feature phase-separated insoluble proteins like collagen and elastin, crucial for structural integrity.

Purpose of the Study:

• To develop injectable hydrogels with phase-separated structures mimicking natural ECM.
• To investigate the effect of inorganic salts on hydrogel phase separation and properties.
• To assess the suitability of these modified hydrogels for cell encapsulation and proliferation.

Main Methods:

• Synthesized injectable hydrogels using mutually cross-linkable tetra-arm poly(ethylene glycol)s.
• Incorporated inorganic salts, specifically potassium sulfate, into the gelling solution.
• Formed phase-separated hydrogel structures in situ upon injection.
• Evaluated hydrogel fracture toughness and encapsulated chondrogenic cell viability and proliferation.

Main Results:

• Achieved in situ formation of phase-separated hydrogel structures by adding potassium sulfate.
• Demonstrated up to an 8-fold increase in hydrogel fracture toughness compared to non-phase-separated counterparts.
• Successfully encapsulated live mouse chondrogenic cells without compromising their proliferative activity.

Conclusions:

• Inorganic salts are a simple yet effective design parameter for creating phase-separated injectable hydrogels.
• Phase-separated injectable hydrogels exhibit enhanced mechanical properties and support cell viability.
• This approach offers a promising strategy for developing advanced artificial ECM materials.