title: Perivascular biodegradable microneedle cuff for reduction of neointima formation after vascular injury.
abstract: Restenosis often occurs at the site of vascular grafting and may become fatal for patients. Restenosis at anastomosis sites is due to neointimal hyperplasia (NH) and difficult to treat with conventional treatments. Such abnormal growth of smooth muscle cells in tunica media of vascular tissue can be reduced by delivering anti-proliferation drugs such as paclitaxel (PTX) to the inner vascular layer. Drug eluting stents (DES) or drug eluting balloon (DEB) have been developed to treat such vascular diseases. However, they are less efficient in drug delivery due to the drug loss to blood stream and inadequate to be applied to re-stenotic area in the presence of stent or anastomosis sites. Recently, we have introduced microneedle cuff (MNC) as perivascular delivery devices to achieve high delivery efficiency to tunica media. In this study, we investigated in vivo microneedle insertion and efficacy in treating NH using a rabbit balloon injury model. Microneedle shape was optimized for reliable insertion into tunica media layer. Uniform distribution of PTX in tunica media delivered by MNC devices was also confirmed. Animal study demonstrated significant NH reduction by MNC treatments and much higher delivery efficiency than flat type devices.
authors.affiliation: School of Mechanical Engineering, Yonsei University, Seoul 120-749, Republic of Korea.
authors.forename: Kang Ju
authors.initials: KJ
authors.lastname: Lee
authors.affiliation: School of Mechanical Engineering, Yonsei University, Seoul 120-749, Republic of Korea.
authors.forename: Seung Hyun
authors.initials: SH
authors.lastname: Park
authors.affiliation: School of Mechanical Engineering, Yonsei University, Seoul 120-749, Republic of Korea.
authors.forename: Ji Yong
authors.initials: JY
authors.lastname: Lee
authors.affiliation: Division of Cardiovascular Surgery, Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea.
authors.forename: Hyun Chel
authors.initials: HC
authors.lastname: Joo
authors.affiliation: Division of Cardiovascular Surgery, Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea.
authors.forename: Eui Hwa
authors.initials: EH
authors.lastname: Jang
authors.affiliation: Division of Cardiovascular Surgery, Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea. Electronic address: ynyoun@yuhs.ac.
authors.forename: Young-Nam
authors.initials: YN
authors.lastname: Youn
authors.affiliation: School of Mechanical Engineering, Yonsei University, Seoul 120-749, Republic of Korea. Electronic address: whryu@yonsei.ac.kr.
authors.forename: WonHyoung
authors.initials: W
authors.lastname: Ryu
mesh_terms: D000818:Animals; D001012:Aorta, Abdominal / Q000187:drug effects / Q000473:pathology*; D004195:Disease Models, Animal; D016503:Drug Delivery Systems / Q000295:instrumentation*; D004867:Equipment Design; D006965:Hyperplasia / Q000473:pathology; D008297:Male; D009339:Needles; D058426:Neointima / Q000188:drug therapy* / Q000473:pathology; D011817:Rabbits; D057772:Vascular System Injuries / Q000150:complications*
keywords: Drug delivery; Grafting surgery; Microneedles; Neointimal hyperplasia; Restenosis