Mechanobiological Mimicry of Helper T Lymphocytes to Evaluate Cell-Biomaterials Crosstalk

The unique properties of immune cells have inspired many efforts in engineering advanced biomaterials capable of mimicking their behaviors. However, an inclusive model capable of mimicking immune cells in different situations remains lacking. Such models can provide invaluable data for understanding immune-biomaterial crosstalk. Inspired by CD4+ T cells, polymeric microparticles with physicochemical properties similar to naïve and active T cells are engineered. A lipid coating is applied to enhance their resemblance and provide a platform for conjugation of desired antibodies. A novel dual gelation approach is used to tune the elastic modulus and flexibility of particles, which also leads to elongated circulation times. Furthermore, the model is enriched with magnetic particles so that magnetotaxis resembles the chemotaxis of cells. Also, interleukin-2, a proliferation booster, and interferon-γ cytokines are loaded into the particles to manipulate the fates of killer T cells and mesenchymal stem cells, respectively. The penetration of these particles into 3D environments is studied to provide in vitro models of immune-biomaterials crosstalk. This biomimicry model enables optimization of design parameters required for engineering more efficient drug carriers and serves as a potent replica for understanding the mechanical behavior of immune cells.