Development and validation of an automated antimicrobial surveillance system based on indications for antimicrobial administration.

INTRODUCTION: We developed an antimicrobial and patient background surveillance system (APBSS), an automated surveillance system that can calculate surveillance data such as antimicrobial use and detection of antimicrobial resistance for each indication of antimicrobial administration. We evaluated the validity of the APBSS data. METHODS: Eligible patients were hospitalized at the Toyota Kosei Hospital on July 7, 2022. Evaluated surveillance data included antimicrobial administration, indications for antimicrobial administration, and diagnosis. In the APBSS, surveillance data were calculated using the Diagnosis Procedure Combination data and Japan Nosocomial Infections Surveillance laboratory data. Using surveillance data collected by the Point Prevalence Survey (PPS) as a reference standard, the agreement between the results calculated based on the APBSS was evaluated using Cohen's kappa coefficient. Indications for antimicrobial administration and diagnosis were analyzed in patients identified for antimicrobial administration in PPS or APBSS. RESULTS: A total of 582 patients were included in this study, 223 of whom were evaluated for indications for antimicrobial administration and diagnosis. For the indications of antimicrobial administration, the Cohen's kappa coefficient was almost perfect (0.81-1.00) for all items. Cohen's kappa coefficient for the diagnosis of healthcare-associated infections was low. However, in major diseases (pneumonia and intra-abdominal, and symptomatic upper urinary tract infections) among community-acquired infections (CAIs) diagnosis, Cohen's kappa coefficient was substantial (0.61-0.80). CONCLUSIONS: The APBSS can identify indications for antimicrobial administration and major CAIs with high accuracy. Therefore, the APBSS can calculate surveillance data, such as antimicrobial use and detection of antimicrobial resistance, for each of these items.

Enhancing cell adhesion in synthetic hydrogels via physical confinement of peptide-functionalized polymer clusters.

Artificially synthesized poly(ethylene glycol) (PEG)-based hydrogels are extensively utilized as biomaterials for tissue scaffolds and cell culture matrices due to their non-protein adsorbing properties. Although these hydrogels are inherently non-cell-adhesive, advancements in modifying polymer networks with functional peptides have led to PEG hydrogels with diverse functionalities, such as cell adhesion and angiogenesis. However, traditional methods of incorporating additives into hydrogel networks often result in the capping of crosslinking points with heterogeneous substances, potentially impairing mechanical properties and obscuring the causal relationships of biological functions. This study introduces polymer additives designed to resist prolonged elution from hydrogels, providing a novel approach to facilitate cell culture on non-adhesive surfaces. By clustering tetra-branched PEG to form ultra-high molecular weight hyper-branched structures and functionalizing their termini with cell-adhesive peptides, we successfully entrapped these clusters within the hydrogel matrix without compromising mechanical strength. This method has enabled successful cell culture on inherently non-adhesive PEG hydrogel surfaces at high peptide densities, a feat challenging to achieve with conventional means. The approach proposed in this study not only paves the way for new possibilities with polymer additives but also serves as a new design paradigm for cell culturing on non-cell-adhesive hydrogels.

Preclustering Gelatin for Faster-Forming Injectable Hydrogels: A Strategy for Fabricating 3D Hydrogel Scaffolds with Improved Cell Dispersion.

Gelatin-based injectable hydrogels capable of encapsulating cells are pivotal in tissue engineering because they can conform to any geometry and exhibit physical properties similar to those of living tissues. However, the slow gelation process observed in these cell-encapsulating hydrogels often causes an uneven dispersion of cells. This study proposes an approach for achieving fast gelation of unmodified gelatin under physiological conditions through gelatin preclustering. By using tetrafunctional succinimidyl-terminated poly(ethylene glycol) as a clustering agent, the gelation process is successfully expedited fivefold without requiring chemical modifications, effectively addressing the associated challenges of uneven cell distribution.

Network of cyano-p-aramid nanofibres creates ultrastiff and water-rich hydrospongels.

The structure-property paradox of biological tissues, in which water-rich porous structures efficiently transfer mass while remaining highly mechanically stiff, remains unsolved. Although hydrogel/sponge hybridization is the key to understanding this phenomenon, material incompatibility makes this a challenging task. Here we describe hydrogel/sponge hybrids (hydrospongels) that behave as both ultrastiff water-rich gels and reversibly squeezable sponges. The self-organizing network of cyano-p-aramid nanofibres holds approximately 5,000 times more water than its solid content. Hydrospongels, even at a water concentration exceeding 90 wt%, are hard as cartilage with an elastic modulus of 50-80 MPa, and are 10-1,000 times stiffer than typical hydrogels. They endure a compressive strain above 85% through poroelastic relaxation and hydrothermal pressure at 120 °C. This performance is produced by amphiphilic surfaces, high rigidity and an interfibrillar, interaction-driven percolating network of nanofibres. These features can inspire the development of future biofunctional materials.

Injectable phase-separated tetra-armed poly(ethylene glycol) hydrogel scaffold allows sustained release of growth factors to enhance the repair of critical bone defects.

With the rising prevalence of bone-related injuries, it is crucial to improve treatments for fractures and defects. Tissue engineering offers a promising solution in the form of injectable hydrogel scaffolds that can sustain the release of growth factors like bone morphogenetic protein-2 (BMP-2) for bone repair. Recently, we discovered that tetra-PEG hydrogels (Tetra gels) undergo gel-gel phase separation (GGPS) at low polymer content, resulting in hydrophobicity and tissue affinity. In this work, we examined the potential of a newer class of gel, the oligo-tetra-PEG gel (Oligo gel), as a growth factor-releasing scaffold. We investigated the extent of GGPS occurring in the two gels and assessed their ability to sustain BMP-2 release and osteogenic potential in a mouse calvarial defect model. The Oligo gel underwent a greater degree of GGPS than the Tetra gel, exhibiting higher turbidity, hydrophobicity, and pore formation. The Oligo gel demonstrated sustained protein or growth factor release over a 21-day period from protein release kinetics and osteogenic cell differentiation studies. Finally, BMP-2-loaded Oligo gels achieved complete regeneration of critical-sized calvarial defects within 28 days, significantly outperforming Tetra gels. The easy formulation, injectability, and capacity for sustained release makes the Oligo gel a promising candidate therapeutic biomaterial.