Person:

Verbeke, Catia

Materials implanted in the body to program host immune cells are a promising alternative to transplantation of ex vivo–manipulated cells to direct an immune response, but required a surgical procedure. Here we demonstrate that high-aspectratio, mesoporous silica rods (MSRs) injected with a needle spontaneously assemble in vivo to form macroporous structures that provide a 3D cellular microenvironment for host immune cells. In mice, substantial numbers of DCs are recruited to the pores between the scaffold rods. The recruitment of DCs and their subsequent homing to lymph nodes can be modulated by sustained release of inflammatory signals and adjuvants from the scaffold. Moreover, injection of an MSR-based vaccine formulation enhances systemic TH1 and TH2 serum antibody and cytotoxic T cell levels compared to bolus controls. These findings suggest that injectable MSRs may serve as a multifunctional vaccine platform to modulate host immune cell function and provoke adaptive immune responses.

The effectiveness of stem-cell therapies has been hampered by cell death and limited control over fate1. These problems can be partially circumvented by using macroporous biomaterials that improve the survival of transplanted stem cells and provide molecular cues to direct cell phenotype2–4. Stem cell behavior can also be controlled in vitro by manipulating the elasticity of both porous and non-porous materials5–7, yet translation to therapeutic processes in vivo remains elusive. Here, by developing injectable, void-forming hydrogels that decouple pore formation from elasticity, we show that mesenchymal stem cell (MSC) osteogenesis in vitro, and cell deployment in vitro and in vivo, can be controlled by modifying, respectively, the hydrogel's elastic modulus or its chemistry. When the hydrogels were used to transplant MSCs, the hydrogel's elasticity regulated bone regeneration, with optimal bone formation at 60 kPa. Our findings show that biophysical cues can be harnessed to direct therapeutic stem-cell behaviors in situ.