Biology subjects

Jones, L. S.

Publications and source records attributed to Jones, L. S..

2 recordsLinked to original sources

bioRxiv2025

Volumetric 3D Printing and Melt-Electrowriting to Fabricate Implantable Reinforced Cardiac Tissue Patches

Cardiac patches for repairing myocardial defects require mechanically stable materials that prevent bleeding and can be implanted via suturing. The current clinical standard, bovine pericardial patches (BPPs), serve this purpose but do not degrade or integrate with the myocardium, limiting their long-term effectiveness. Therefore, we have developed the Reinforced engineered Cardiac tissue Patch (RCPatch). This multimaterial patch consists of a stiffness-tuned, cardiomyocyte-infiltrated 3D metamaterial and a suturable, hydrogel-infiltrated mesh to reduce permeability and bleeding. We first designed and computationally optimized anisotropic metamaterials using a generative modelling approach and fabricated them from biodegradable poly({varepsilon}-caprolactone) (PCL) via volumetric 3D printing (VP). The metamaterial supported the infiltration of cardiomyocytes, which maintained cell viability and contractility in vitro. In a second step, we enhanced implantability and reduced blood permeability through the patch by combining a melt-electrowritten (MEW) mesh with a fibrin hydrogel. Finally, in an acute large animal trial, the RCPatch was used on an induced myocardial defect, where it withstood intraventricular blood pressure and enabled partial hemodynamic recovery. Our findings establish a scalable framework for fabricating cardiac tissue patches that integrate mechanical reinforcement with biological function, offering a surgically implantable, and potentially regenerative solution for intraventricular myocardial repair. Table of Contents (ToC) O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=179 SRC="FIGDIR/small/642643v1_ufig1.gif" ALT="Figure 1"> View larger version (64K): org.highwire.dtl.DTLVardef@66293dorg.highwire.dtl.DTLVardef@11d9122org.highwire.dtl.DTLVardef@235d16org.highwire.dtl.DTLVardef@1b46911_HPS_FORMAT_FIGEXP M_FIG C_FIG This study presents an implantable intraventricular cardiac patch (RCPatch) combining volumetric 3D-printed metamaterials with melt-electrowritten (MEW) meshes. The design integrates tunable stiff structures with soft, cell-laden hydrogels. The RCPatch withstood suturing, intraventricular pressure, and cardiac contraction in an acute large animal myocardial defect model. The patch prevented bleeding and enabled partial hemodynamic recovery, demonstrating its potential for myocardial repair.

bioengineering↗

bioRxiv2022

Genomic surveillance of carbapenem-resistant Klebsiella in Wales reveals persistent spread of K. pneumoniae ST307 and adaptive evolution of pOXA-48-like plasmids

Rising rates of multi-drug resistant Klebsiella infections necessitate a comprehensive understanding of the major strains and plasmids driving spread of resistance elements. Here we analysed 540 Klebsiella isolates recovered from patients across Wales between 2007 and 2020 using combined short- and long-read sequencing approaches. We identified resistant clones that have spread within and between hospitals including the high-risk strain, sequence type (ST) 307, which acquired the blaOXA-244 carbapenemase gene on a pOXA-48-like plasmid. We found evidence that this strain, which caused an acute outbreak largely centred on a single hospital in 2019, had been circulating undetected across South Wales for several years prior to the outbreak. In addition to clonal transmission, our analyses revealed evidence for substantial plasmid spread, mostly notably involving blaKPC-2 and blaOXA-48-like (including blaOXA-244) carbapenemase genes that were found among many species and strain backgrounds. Two thirds (20/30) of the blaKPC-2 genes were carried on the Tn4401a transposon and associated with IncF plasmids. These were mostly recovered from patients in North Wales, reflecting an outward expansion of the plasmid-driven outbreak of blaKPC-2-producing Enterobacteriaceae in North-West England. 92.1% (105/114) of isolates with a blaOXA-48-like carbapenemase carried the gene on a pOXA-48-like plasmid. While this plasmid family is highly conserved, our analyses revealed novel accessory variation including integrations of additional resistance genes. We also identified multiple independent deletions involving the tra gene cluster among pOXA-48-like plasmids in the ST307 outbreak lineage. These resulted in loss of conjugative ability and signal adaptation of the plasmids to carriage by the host strain. Altogether, our study provides the first high resolution view of the diversity, transmission and evolutionary dynamics of major resistant clones and plasmids of Klebsiella in Wales and forms an important basis for ongoing surveillance efforts. Data SummaryAll raw short read sequence data and hybrid assemblies are available in the European Nucleotide Archive (ENA) under project accession PRJEB48990.

microbiology↗