Stability of a biodegradable microcarrier surface: physically adsorbed versus chemically linked shells.

Area of Science:

• Biomaterials Science
• Tissue Engineering
• Cellular Therapy

Background:

• Mesenchymal stem cells (MSCs) are vital for tissue engineering and cellular therapy.
• Microcarriers (MCs) in bioreactors offer a scalable method for MSC expansion.
• Existing polyester-based MCs often use non-degradable stabilizers and have loosely adsorbed shells, raising concerns about stability in culture media.

Purpose of the Study:

• To develop and evaluate in vivo bioresorbable, dextran-covered polylactide-based MCs with enhanced shell stability.
• To investigate the impact of click-chemistry linkage on shell integrity against surfactants and proteins.

Main Methods:

• Formulation of polylactide core MCs with dextran shells using emulsion/organic solvent evaporation (E/E).
• Synthesis of dextran derivatives with alkyne or ammonium groups.
• Comparison of physically adsorbed (non-clicked) vs. covalently linked (clicked) dextran shells via in situ CuAAC click-chemistry.
• Stability testing using nanoparticles and MCs in the presence of sodium dodecyl sulfate (SDS) and cell culture medium.

Main Results:

• Non-clicked dextran shells completely desorbed in SDS and culture medium.
• Clicked dextran shells exhibited significantly reduced desorption under the same conditions.
• Fluorescently labeled clicked MCs demonstrated superior shell stability compared to non-clicked MCs in the presence of surfactants.

Conclusions:

• Covalently linking dextran shells to polylactide cores via click-chemistry greatly improves their stability.
• Clicked MCs offer better control over surface chemistry, which is critical for scalable MSC expansion in bioreactors.
• This advancement addresses limitations of current MCs, paving the way for more robust cellular therapies.