Titanium implants have been widely used in bone tissue engineering for decades. However, orthopedic implant-associated infections increase the risk of implant failure and even lead to amputation in severe cases. Although TiO2 has photocatalytic activity to produce reactive oxygen species (ROS), the recombination of generated electrons and holes limits its antibacterial ability. Here, we describe a graphdiyne (GDY) composite TiO2 nanofiber that combats implant infections through enhanced photocatalysis and prolonged antibacterial ability. In addition, GDY-modified TiO2 nanofibers exert superior biocompatibility and osteoinductive abilities for cell adhesion and differentiation, thus contributing to the bone tissue regeneration process in drug-resistant bacteria-induced implant infection.
Sensory neurons promote profound
suppressive effects on neutrophils
during Streptococcus pyogenes infection and contribute
to the pathogenesis of necrotizing infection (“flesh-eating
disease”). Thus, the development of new antibacterial agents
for necrotizing infection is promising because of the clear streptococcal
neuro-immune communication. Herein, based on the immune escape membrane
exterior and competitive membrane functions of the glioma cell membrane,
a novel nano neuro-immune blocker capsule was designed to prevent
neuronal activation and improve neutrophil immune responses for necrotizing
infection. These nano neuro-immune blockers could neutralize streptolysin
S, suppress neuron pain conduction and calcitonin gene-related peptide
release, and recruit neutrophils to the infection site, providing
a strong therapeutic effect against necrotizing infection. Furthermore,
nano neuro-immune blockers could serve as an effective inflammatory
regulator and antibacterial agent via photothermal effects under near-infrared
irradiation. In the Streptococcus pyogenes-induced
necrotizing fasciitis mouse model, nano neuro-immune blockers showed
significant therapeutic efficacy by ameliorating sensitivity to pain
and promoting the antibacterial effect of neutrophils.
The immune response of a biomaterial determines its osteoinductive effect. Although the mechanisms by which some immune cells promote regeneration have been revealed, the biomaterial-induced immune response is a dynamic process involving multiple cells. Currently, it is challenging to accurately regulate the innate and adaptive immune responses to promote osteoinduction in biomaterials. Herein, we investigated the roles of macrophages and dendritic cells (DCs) during the osteoinduction of biphasic calcium phosphate (BCP) scaffolds. We found that osteoinductive BCP directed M2 macrophage polarization and inhibited DC maturation, resulting in low T cell response and efficient osteogenesis. Accordingly, a dual-targeting nano-in-micro scaffold (BCP loaded with gold nanocage, BCP-GNC) was designed to regulate the immune responses of macrophages and DCs. Through a dual-wavelength photosensitive switch, BCP-GNC releases interleukin-4 in the early stage of osteoinduction to target M2 macrophages and then releases dexamethasone in the later stage to target immature DCs, creating a desirable inflammatory environment for osteogenesis. This study demonstrates that biomaterials developed to have specific regulatory capacities for immune cells can be used to control the early inflammatory responses of implanted materials and induce osteogenesis.
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