Advanced Injectable Human-Derived Microgels for Improved Cell Delivery and Tissue Regeneration

Abstract

The development of effective cell delivery therapies faces challenges regarding cell viability and retention after injection. Hydrogel-based materials, designed to mimic extracellular matrix components for cell protection during injection and to enhance local availability, often rely on animal-derived components that raise immunogenicity concerns. Alternatively, those employing polysaccharides and synthetic polymers may exhibit suboptimal cell adhesive properties. This study showcases the development of injectable human protein-derived cell carrier microgels made from methacryloyl platelet lysates. These microgels sustain cell viability by providing an enriched and cost-effective environment of growth factors and proteins while promoting the outward migration of mesenchymal stem cells through controlled enzyme-mediated degradation. Employing a solvent-free and reproducible method using superhydrophobic surfaces, human-derived microgels are successfully fabricated via light irradiation, with sizes adjustable by varying droplet volume. Additionally, the incorporation of collagenase facilitates enzyme-mediated cell migration without compromising viability. Injectability tests confirm that microgel administration preserves both size and morphology, and their effectiveness in filling irregular defects in a porcine tissue highlights their suitability for therapeutic applications. Ultimately, these microgels can be modified to include magnetic nanoparticles, enabling spatial control and fixation using an external magnetic field, and potential imaging capabilities, positioning them as promising candidates for personalized cell therapies.