RESUMO
Hydrogels are widely used for tissue engineering applications to support cellular growth, yet the tightly woven structure often restricts cell infiltration and expansion. Consequently, granular hydrogels with microporous architectures have emerged as a new class of biomaterial. Particularly, the development of microporous annealed particle (MAP) hydrogel scaffolds has shown improved stability and integration with host tissue. However, the predominant use of spherically shaped particles limits scaffold porosity, potentially limiting the level of cell infiltration. Here, a novel microporous annealed crescent-shaped particle (MAC) scaffold that is predicted to have improved porosity and pore interconnectivity in silico is presented. With microfluidic fabrication, tunable cavity sizes that optimize interstitial void space features are achieved. In vitro, cells incorporated into MAC scaffolds form extensive 3D multicellular networks. In vivo, the injectable MAC scaffold significantly enhances cell infiltration compared to spherical MAP scaffolds, resulting in increased numbers of myofibroblasts and leukocytes present within the gel without relying on external biomolecular chemoattractants. The results shed light on the critical role of particle shape in cell recruitment, laying the foundation for MAC scaffolds as a next-generation granular hydrogel for diverse tissue engineering applications.
RESUMO
New vaccine platforms that activate humoral immunity and generate neutralizing antibodies are required to combat emerging pathogens, including influenza virus. A slurry of antigen-loaded hydrogel microparticles that anneal to form a porous scaffold with high surface area for antigen uptake by infiltrating immune cells as the biomaterial degrades is demonstrated to enhance humoral immunity. Antigen-loaded-microgels elicited a robust cellular humoral immune response, with increased CD4+ T follicular helper (Tfh) cells and prolonged germinal center (GC) B cells comparable to the commonly used adjuvant, aluminum hydroxide (Alum). Increasing the weight fraction of polymer material led to increased material stiffness and antigen-specific antibody titers superior to Alum. Vaccinating mice with inactivated influenza virus loaded into this more highly cross-linked formulation elicited a strong antibody response and provided protection against a high dose viral challenge. By tuning physical and chemical properties, adjuvanticity can be enhanced leading to humoral immunity and protection against a pathogen, leveraging two different types of antigenic material: individual protein antigen and inactivated virus. The flexibility of the platform may enable design of new vaccines to enhance innate and adaptive immune cell programming to generate and tune high affinity antibodies, a promising approach to generate long-lasting immunity.