Nanofunctionalized Microparticles for Glucose Delivery in Three-Dimensional Cell Assemblies

Area of Science:

• Biomaterials Engineering
• Cell Biology
• Tissue Engineering

Background:

• Three-dimensional (3D) cell spheroids mimic native tissue microenvironments but face nutrient diffusion limitations, leading to necrosis.
• Large spheroids suffer from insufficient oxygen and nutrient penetration, restricting their application.

Purpose of the Study:

• To develop a novel strategy using nanoparticle-coated microparticles to enhance nutrient diffusion and cell viability in 3D spheroids.
• To create a localized nutrient delivery system within human mesenchymal stem cell (hMSC) spheroids.

Main Methods:

• Poly(lactic-co-glycolic acid) (PLGA) microparticles were coated with mesoporous silica nanoparticles (MSNs) via electrostatic interactions.
• MSN-coated PLGA microparticles were incorporated into hMSC spheroids to form nanofunctionalized microparticle spheroids.
• Glucose release kinetics and the impact on spheroid aggregation and cell viability were evaluated over 14 days.

Main Results:

• The MSN coating on PLGA microparticles demonstrated stability during incubation.
• MSN-coated PLGA microparticles facilitated the formation of homogeneous hMSC spheroids with good cell viability.
• Local glucose delivery from MSNs within spheroids significantly enhanced cell viability under hypoxic conditions.

Conclusions:

• The developed nanofunctionalized microparticle system provides a versatile platform for localized small molecule delivery in 3D cell cultures.
• This approach effectively improves cell viability in spheroids by addressing nutrient diffusion challenges.
• The strategy holds promise for advancing applications in tissue engineering and regenerative medicine.