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Open Access Publications from the University of California

Scholarly Works (4 results)

  • Thesis
  • Peer Reviewed
UC Berkeley Electronic Theses and Dissertations (2016)

Biodegradable polymers have potential as a scaffold material for making small diameter artery bypass grafts. To resist thrombosis, maintain biocompatibility and enhance the remodeling of the grafts, it is crucial to modify polymer scaffolds so that the grafts have anti-thrombogenic capacity and allow cell infiltration. In this study, two methods of aminolysis on electrospun poly-lactide-co-caprolactone (PLCL) nanofibers vascular graft are compared: plasma treatment method and Fmoc-PEG-diamine insertion method. Both methods successfully inserted amino groups on the polymer graft for heparin conjugation. However, plasma treatment resulted in significantly higher initial heparin density and higher heparin stability under simulated physiological conditions on PLCL nanofibers than Fmoc-PEG-diamine treatment. In addition, mechanical testing demonstrated that the plasma treatment method maintained PLCL nanofiber tensile strength after heparin conjugation while Fmoc-PEG-diamine insertion method compromised the mechanical property due to partial fiber melting and structure disruption. Subcutaneous implantation of the grafts in a rat model showed that heparin coating with both methods promoted cell infiltration. This study provides a rationale to optimize the biomolecule conjugation on electrospun PLCL scaffolds, and will have applications in tissue engineering vascular grafts and other tissues.

    Cover page: In situ vascular graft generation and drug delivery system modeled by stromal cell- derived factor 1a and polylactide-co-caprolactone
    • Article
    • Peer Reviewed
    UCLA Previously Published Works (2021)
    The remodeling of vascular grafts is critical for blood vessel regeneration. However, most scaffold materials have limited cell infiltration. In this study, we designed and fabricated a scaffold that incorporates a fast-degrading polymer polydioxanone (PDO) into the microfibrous structure by means of electrospinning technology. Blending PDO with base polymer decreases the density of electrospun microfibers yet did not compromise the mechanical and structural properties of the scaffold, and effectively enhanced cell infiltration. We then used this technique to fabricate a tubular scaffold with heparin conjugated to the surface to suppress thrombosis, and the construct was implanted into the carotid artery as a vascular graft in animal studies. This graft significantly promoted cell infiltration, and the biochemical cues such as immobilized stromal cell-derived factor-1α further enhanced cell recruitment and the long-term patency of the grafts. This work provides an approach to optimize the microfeatures of vascular grafts, and will have broad applications in scaffold design and fabrication for regenerative engineering.
      Cover page: Engineering the Composition of Microfibers to Enhance the Remodeling of a Cell-Free Vascular Graft
      • Article
      • Peer Reviewed
      UC Berkeley Previously Published Works (2018)
      RNA-based fluorescent (RBF) biosensors have been applied to detect a variety of metabolites in vitro and in live cells. They are designed by combining the ligand sensing domain of natural riboswitches with in vitro selected fluorogenic aptamers. Different biosensor topologies have been developed to accommodate the diversity of riboswitch structures. Here we show that circular permutation of the riboswitch ligand sensing domain also gives functional biosensors, using the SAM-I riboswitch as our model. We reveal that this design can enhance fluorescence turn-on and ligand binding affinity compared to the non-permuted topology.
        • Article
        • Peer Reviewed
        UC Berkeley Previously Published Works (2015)
        Cyclic dinucleotides are an expanding class of signaling molecules that control many aspects of bacterial physiology. A synthase for cyclic AMP-GMP (cAG, also referenced as 3'-5', 3'-5' cGAMP) called DncV is associated with hyperinfectivity of Vibrio cholerae but has not been found in many bacteria, raising questions about the prevalence and function of cAG signaling. We have discovered that the environmental bacterium Geobacter sulfurreducens produces cAG and uses a subset of GEMM-I class riboswitches (GEMM-Ib, Genes for the Environment, Membranes, and Motility) as specific receptors for cAG. GEMM-Ib riboswitches regulate genes associated with extracellular electron transfer; thus cAG signaling may control aspects of bacterial electrophysiology. These findings expand the role of cAG beyond organisms that harbor DncV and beyond pathogenesis to microbial geochemistry, which is important to environmental remediation and microbial fuel cell development. Finally, we have developed an RNA-based fluorescent biosensor for live-cell imaging of cAG. This selective, genetically encodable biosensor will be useful to probe the biochemistry and cell biology of cAG signaling in diverse bacteria.
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