Urinary tract infections (UTIs) are a major public health problem affecting millions of individuals each year. Recurrent UTIs are managed by long-term antibiotic use, making the alarming rise of antibiotic resistance a substantial threat to future UTI treatment. Extended antibiotic regimens may also have adverse effects on the microbiome. Here, we report the use of a supramolecular vaccine to provide long-term protection against uropathogenic Escherichia coli , which cause 80% of uncomplicated UTIs. We designed mucus-penetrating peptide-polymer nanofibers to enable sublingual (under the tongue) vaccine delivery and elicit antibody responses systemically and in the urogenital tract. In a mouse model of UTI, we demonstrate equivalent efficacy to high-dose oral antibiotics but with significantly less perturbation of the gut microbiome. We also formulate our vaccine as a rapid-dissolving sublingual tablet that raises response in mice and rabbits. Our approach represents a promising alternative to antibiotics for the treatment and prevention of UTIs.
Microporous annealed particle scaffolds (MAPS) are a new class of granular materials generated through the interlinking of tunable microgels, which produce an interconnected network of void space. These microgel building blocks can be designed with different mechanical or bio‐active parameters to facilitate cell infiltration and modulate host response. Previously, changing the chirality of the microgel crosslinking peptides from L‐ to D‐amino acids led to significant tissue regeneration and functional recovery in D‐MAPS‐treated cutaneous wounds. In this study, the immunomodulatory effect of D‐MAPS in a subcutaneous implantation model is investigated. How macrophages are the key antigen‐presenting cells to uptake and present these biomaterials to the adaptive immune system is uncovered. A robust linker‐specific IgG2b/IgG1 response to D‐MAPS is detected as early as 14 days post‐implantation. The fine balance between pro‐regenerative and pro‐inflammatory macrophage phenotypes is observed in D‐MAPS as an indicator for regenerative scaffolds. The work offers valuable insights into the temporal cellular response to synthetic porous scaffolds and establishes a foundation for further optimization of immunomodulatory pro‐regenerative outcomes.
Microporous annealed particle scaffolds (MAPS) are a new class of granular materials generated through the interlinking of tunable microgels, which produce an interconnected network of void space. These microgel building blocks can be designed with different mechanical or bio-active parameters to facilitate cell infiltration and modulate host response. Previously, changing the chirality of the microgel crosslinking peptides from L- to D-amino acids led to significant tissue regeneration and functional recovery in D-MAPS-treated cutaneous wounds. In this study, we investigated the immunomodulatory effect of D-MAPS in a subcutaneous implantation model. We uncovered how macrophages are the key antigen-presenting cells to uptake and present these biomaterials to the adaptive immune system. A robust linker-specific IgG2b/IgG1 response to D-MAPS was detected as early as 14 days post-implantation. The fine balance between pro-regenerative and pro-inflammatory macrophage phenotypes was observed in D-MAPS as an indicator for regenerative scaffolds. Our work offers valuable insights into the temporal cellular response to synthetic porous scaffolds and establishes a foundation for further optimization of immunomodulatory pro-regenerative outcomes.
The quality and yield of the monoclonal antibodies produced in a cGMP environment is heavily influenced by the bioprocess-related parameters which impact the cell growth and metabolism of the mammalian cell cultures. This research report describes a study conducted to examine the effects of varying temperature and RPM set points on viable cell density and viability of NS0 cultures. All cultures were grown in 250 mL shake flasks (working vol. 100 mL). To separately analyze the effects of temperature and agitation rate on NS0 cell metabolism, flask stage cultures were evaluated in triplicates at two cultivation temperatures (36 °C and 38 °C) and two agitation rates (120 RPM and 160 RPM) while controls were maintained at 37 °C and 140 RPM for both the conditions using an incubator. Flasks were sampled every 24 h and analyzed for viable cell density and % viability. Additional data was collected on pH, pO2, pCO2, osmolality, glucose, lactate, glutamate and glutamine levels in the culture. It was observed that variations in temperature has the greatest effect on viable cell density and viability and varying agitation rates had minimal effect on growth of cultures. A temperature set point of 38 °C is detrimental to the culture growth. The control set points proved to be optimal for this process.
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