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The Control of Drug Release and Vascular Endothelialization after Hyaluronic Acid-Coated Paclitaxel Multi-Layer Coating Stent Implantation in Porcine Coronary Restenosis Model

  • Bae, In-Ho (The Cardiovascular Convergence Research Center of Chonnam National University Hospital, Designated by Korea Ministry of Health and Welfare) ;
  • Jeong, Myung Ho (The Cardiovascular Convergence Research Center of Chonnam National University Hospital, Designated by Korea Ministry of Health and Welfare) ;
  • Kim, Ju Han (Korea Cardiovascular Stent Research Institute) ;
  • Park, Yong Hwan (Korea Cardiovascular Stent Research Institute) ;
  • Lim, Kyung Seob (The Cardiovascular Convergence Research Center of Chonnam National University Hospital, Designated by Korea Ministry of Health and Welfare) ;
  • Park, Dae Sung (The Cardiovascular Convergence Research Center of Chonnam National University Hospital, Designated by Korea Ministry of Health and Welfare) ;
  • Shim, Jae Won (The Cardiovascular Convergence Research Center of Chonnam National University Hospital, Designated by Korea Ministry of Health and Welfare) ;
  • Kim, Jung Ha (The Cardiovascular Convergence Research Center of Chonnam National University Hospital, Designated by Korea Ministry of Health and Welfare) ;
  • Ahn, Youngkeun (Korea Cardiovascular Stent Research Institute) ;
  • Hong, Young Joon (Korea Cardiovascular Stent Research Institute) ;
  • Sim, Doo Sun (Korea Cardiovascular Stent Research Institute)
  • Received : 2016.05.20
  • Accepted : 2016.10.07
  • Published : 2017.01.31

Abstract

Background and Objectives: Hyaluronic acid (HA) is highly biocompatible with cells and the extracellular matrix. In contrast to degradation products of a synthetic polymer, degradation products of HA do not acidify the local environment. The aim of this study was to fabricate an HA-coated paclitaxel (PTX)-eluting stent via simple ionic interactions and to evaluate its effects in vitro and in vivo. Materials and Methods: HA and catechol were conjugated by means of an activation agent, and then the stent was immersed in this solution (resulting in a HA-coated stent). After that, PTX was immobilized on the HA-coated stent (resulting in a hyaluronic acid-coated paclitaxel-eluting stent [H-PTX stent]). Study groups were divided into 4 groups: bare metal stent (BMS), HA, H-PTX, and poly (L-lactide)-coated paclitaxel-eluting stent (P-PTX). Stents were randomly implanted in a porcine coronary artery. After 4 weeks, vessels surrounding the stents were isolated and subjected to various analyses. Results: Smoothness of the surface was maintained after expansion of the stent. In contrast to a previous study on a PTX-eluting stent, in this study, the PTX was effectively released up to 14 days (a half amount of PTX in 4 days). The proliferation of smooth muscle cells was successfully inhibited (by $80.5{\pm}12.11%$ at 7 days of culture as compared to the control) by PTX released from the stent. Animal experiments showed that the H-PTX stent does not induce an obvious inflammatory response. Nevertheless, restenosis was clearly decreased in the H-PTX stent group ($9.8{\pm}3.25%$) compared to the bare-metal stent group ($29.7{\pm}8.11%$). Conclusion: A stent was stably coated with PTX via simple ionic interactions with HA. Restenosis was decreased in the H-PTX group. These results suggest that HA, a natural polymer, is suitable for fabrication of drug-eluting stents (without inflammation) as an alternative to a synthetic polymer.

Keywords

Acknowledgement

Supported by : Korean Society of Cardiology

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