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Open Access Publications from the University of California

Scholarly Works (2 results)

  • Thesis
  • Peer Reviewed
UC San Francisco Electronic Theses and Dissertations (2015)

Current approaches to reducing restenosis do not balance the reduction of vascular smooth muscle cell proliferation with the increase in the healing of the endothelium. Here, I present my study on the synthesis and characterization of a nanotubular coating on Nitinol substrates. I found that the coating demonstrated ‘pro-healing’ properties by increasing primary human aortic endothelial cell spreading, migration and collagen and elastin production. Certain cellular functions such as collagen and elastin production were also found to be affected by changes in nanotube diameter. The coating also reduced the proliferation and mRNA expression of collagen I and MMP2 for primary human aortic smooth muscle cells. I will also demonstrate the synthesis of a nanowell coating on Nitinol stents as well as an additional poly(lactic-co-glycolic acid) coating on top of the nanowells that has the potential for controlling drug release. These findings demonstrate the potential for the coatings to aid in the prevention of restenosis and sets up future explorations of ex vivo and in vivo studies.

    Cover page: Nitinol-based Nanotubular and Nanowell Coatings for the Modulation of Human Vascular Cell Functions
    • Article
    • Peer Reviewed
    UC San Francisco Previously Published Works (2017)
    Resolvin D1 (RvD1) belongs to a family of endogenously derived proresolving lipid mediators that have been shown to attenuate inflammation, activate proresolution signaling, and promote homeostasis and recovery from tissue injury. In this study we present a poly(lactic-co-glycolic acid) (PLGA) based thin-film device composed of layers of varying ratios of lactic and glycolic acid that elutes RvD1 unidirectionally to target tissues. The device demonstrated sustained release in vitro for 56 days with an initial burst of release over 14 days. The asymmetric design of the device released 98% of RvD1 through the layer with the lowest molar ratio of lactic acid to glycolic acid, and the remainder through the opposite side. We validated structural integrity of RvD1 released from the device by mass spectrometry and investigated its bioactivity on human vascular endothelial (EC) and smooth muscle cells (VSMC). RvD1 released from the device attenuated VSMC migration, proliferation, and TNF-α induced NF-κB activation, without evidence of cytotoxicity. Delivery of RvD1 to blood vessels was demonstrated ex vivo in a flow chamber system using perfused rabbit aortas and in vivo in a rat carotid artery model, with the devices applied as an adventitial wrap. Our results demonstrate a novel approach for sustained, local delivery of Resolvin D1 to vascular tissue at therapeutically relevant levels. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 31-41, 2017.
      Cover page: Unidirectional and sustained delivery of the proresolving lipid mediator resolvin D1 from a biodegradable thin film device
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