Kristiansenalbright3653

The alarming increase of antibiotic-resistant bacteria, causing conventional treatments of bacterial infections to become increasingly inefficient, is one of the biggest threats to global health. Here, we have developed probiotic cellulose, an antibiotic-free biomaterial for the treatment of severe skin infections and chronic wounds. This composite biomaterial was in-depth characterized by Gram stain, scanning electron microscopy (SEM) and confocal fluorescence microscopy. Results demonstrated that probiotic cellulose consists of dense films of cellulose nanofibers, free of cellulose-producing bacteria, completely invaded by live probiotics (Lactobacillus fermentum or Lactobacillus gasseri). Viability assays, including time evolution of pH and reducing capacity against electrochromic polyoxometalate, confirmed that probiotics within the cellulose matrix are not only alive but also metabolically active, a key point for the use of probiotic cellulose as an antibiotic-free antibacterial biomaterial. Antibacterial assays in pathogen-favorable media, a real-life infection scenario, demonstrated that probiotic cellulose strongly reduces the viability of Staphylococcus aureus (SA) and Pseudomonas aeruginosa (PA), the most active pathogens in severe skin infections and chronic wounds. Likewise, probiotic cellulose was also found to be effective to inhibit the proliferation of methicillin-resistant SA (MRSA). The combination of the properties of bacterial cellulose as wound dressing biomaterial and the antibacterial activity of probiotics makes probiotic cellulose an alternative to antibiotics for the treatment of topical infections, including severe and hard-to-heal chronic wounds. In addition, probiotic cellulose was obtained by a one-pot synthetic approach under mild conditions, not requiring the long and expensive chemical treatments to purify the genuine bacterial cellulose.Establishing an adequate vascularization of three-dimensional (3D) bioengineered tissues remains a critical challenge. We previously fabricated a vascular scaffold using the vascular corrosion casting technique, which provides a similar 3D geometry of native kidney vasculature. In this study, we functionalized the collagen vascular scaffold with a controlled release of vascular endothelial growth factor (VEGF vascular scaffold) to further promote vascularization. The VEGF vascular scaffold showed improved angiogenic capability in 2-dimensional (2D) and 3D in vitro settings. Implantation of the VEGF vascular scaffold seeded with human renal cells into a rat kidney demonstrated enhanced implant vascularization and reduced apoptosis of implanted human renal cells. Hybrid renal tubule-like structures composed of implanted human and migrated host renal cells were formed. This work highlights the critical role of early vascularization of the geometrically mimetic vascular scaffold using the VEGF incorporated vascular scaffold in reducing apoptosis of implanted cells as well as the formation of renal tissue structures.Arginase 1 (ARG1) inactivates T cells by degrading L-arginine, severely reducing the immunotherapeutic efficacy. Effectively blocking the ARG1 pathway remains a challenge. L-norvaline is a very cheap and negligible side effects inhibitor of ARG1. However, its blockage efficacy for ARG1 is impeded by its high half-maximal-inhibitory concentration (IC50) requiring high drug loading content of L-norvaline in carriers. Moreover its high water solubility results in bursting and uncontrolled release. Herein we reported an injectable hydrogel strategy via an L-norvaline-based immunomodulating gelator that could effectively block ARG1 pathway. The designed gelator was a diblock copolymer containing L-norvaline-based polypeptide block, which could construct a thermally responsive injectable hydrogel by its self-gelation in tumor microenvironments. The hydrogel not only ensures high drug loading of L-norvaline, but also ensures controlled release of L-norvaline through responsive peptide bond cleavage, thereby solving ine. Selleckchem Prexasertib By further introducing doxorubicin hydrochloride in the hydrogel for inducing immunogenic cell death, the hydrogel showed remarkable immunotherapeutic efficacy towards ablation of primary tumors, suppression of abscopal tumors and inhibition of pulmonary metastasis. Our immunomodulating gelator strategy provides a new concept to efficiently reverse Arginase 1 immunosuppressive environments for amplified immunotherapy.Diabetic wound healing remains a major challenge due to its vulnerability to bacterial infection, as well as the less vascularization and prolonged inflammatory phase. In this study, we developed a hydrogel system for the treatment of chronic infected wounds, which can regulate inflammatory (through the use of antimicrobial peptides) and enhance collagen deposition and angiogenesis (through the addition of platelet-rich plasma (PRP)). Based on the formation of Schiff base linkage, the ODEX/HA-AMP/PRP hydrogel was prepared by mixing oxidized dextran (ODEX), antimicrobial peptide-modified hyaluronic acid (HA-AMP) and PRP under physiological conditions, which exhibited obvious inhibition zones against three pathogenic bacterial strains (E. coli, S. aureus and P. aeruginosa) and slow release ability of antimicrobials and growth factors. Moreover, CCK-8, live/dead fluorescent staining and scratch test confirmed that ODEX/HA-AMP/PRP hydrogel could facilitate the proliferation and migration of L929 fibroblast cells. More importantly, in vivo experiments further demonstrated that the prepared hydrogels could significantly improve wound healing in a diabetic mouse infection by regulating inflammation, accelerating collagen deposition and angiogenesis. In addition, prepared hydrogel showed a significant antibacterial activity against S. aureus and P. aeruginosa, inhibited pro-inflammatory factors (TNF-α, IL-1β and IL-6), enhanced anti-inflammatory factors (TGF-β1) and vascular endothelial growth factor (VEGF) production. The findings of this study suggested that the composite hydrogel with AMP and PRP controlled release ability could be used as a promising candidate for chronic wound healing and infection-related wound healing.