Exploiting the preferential phagocytic uptake of nanoparticle-antigen conjugates for the effective treatment of autoimmunity.

Tolerance induction is central to the suppression of autoimmunity. Here, we engineered the preferential uptake of nano-conjugated autoantigens by spleen-resident macrophages to re-introduce self-tolerance and suppress autoimmunity. The brain autoantigen, myelin oligodendrocyte glycoprotein (MOG), was conjugated to 200 or 500 nm silica nanoparticles (SNP) and delivered to the spleen and liver-resident macrophages of experimental autoimmune encephalomyelitis (EAE) mice, used as a model of multiple sclerosis. MOG-SNP conjugates significantly reduced signs of EAE at a very low dose (50 µg) compared to the higher dose (>800 µg) of free-MOG. This was associated with reduced proliferation of splenocytes and pro-inflammatory cytokines secretion, decreased spinal cord inflammation, demyelination and axonal damage. Notably, biodegradable porous SNP showed an enhanced disease suppression assisted by elevated levels of regulatory T cells and programmed-death ligands (PD-L1/2) in splenic and lymph node cells. Our results demonstrate that targeting nano-conjugated autoantigens to tissue-resident macrophages in lymphoid organs can effectively suppress autoimmunity.

Superhydrophilic multifunctional nanotextured titanium dental implants: in vivo short and long-term response in a porcine model.

Current clinical demand in dental implantology is for a multifunctional device with optimum mechanical properties, improved biocompatibility and bioactivity, and having differential interactions with cells and pathogenic agents. This would minimise bacterial infection, biofilm formation and modulate inflammation, leading to a fast and durable osseointegration. The present study intends to establish the multifunctional behaviour of surface modified titanium dental implants that are superhydrophilic, with unique micro-nano or nanoscale topographies, developed by a facile hydrothermal technique. Here, the short and long-term performances of these textured implants are tested in a split mouth design using a porcine model, in pre- and post-loaded states. Quantitative and qualitative analyses of the bone implant interphase are performed through µ-CT and histology. Parameters that evaluate bone mineral density, bone contact volume and bone implant contact reveal enhanced bone apposition with better long-term response for the nano and micro-nano textured surfaces, compared to the commercial microtextured implant. Concurrently, the nanoscale surface features on implants reduced bacterial attachment by nearly 90% in vivo, outperforming the commercial variant. This preclinical evaluation data thus reveal the superiority of nano/micro-nano textured designs for clinical application and substantiate their improved osseointegration and reduced bacterial adhesion, thus proposing a novel dental implant with multifunctional characteristics.