Copyright © 2014 American Scientific Publishers All rights reserved Printed in the United States of America Article Journal of Biomedical Nanotechnology Vol. 10, 1194–1204, 2014 www.aspbs.com/jbn Novel Biodegradable Drug-Eluting Stent Composed of Poly-L-Lactic Acid and Amorphous Calcium Phosphate Nanoparticles Demonstrates Improved Structural and Functional Performance for Coronary Artery Disease Zhiyuan Lan 1 2† PhD, Yongnan Lyu 3† MD, Jianmin Xiao 4† MD, Xiaoxin Zheng 3 MD, Suyuan He 3 MD, Gaoke Feng 3 MD, Yipei Zhang 2 MS, Shihang Wang 2 MS, Edward Kislauskis 2 PhD, Jiuhao Chen 4 MD, Stephen McCarthy 1 PhD, Roger Laham 5 MD, Xuejun Jiang 3 ∗ MD, PhD, and Tim Wu 1 2 ∗ MD 1 Department of Plastic Engineering, University of Massachusetts Lowell, Lowell, MA, 01854, USA 2 VasoTech, Inc., Lowell, 600 Suffolk St, Lowell, MA 01854, USA 3 Cardiovascular Division, Renmin Hospital of Wuhan University, Wuhan 430060, China 4 Cardiovascular Division,Taiping Renmin Hospital, Dongguan 523905, P. R. C. 5 Beth Israel Deaconess Medical Center, Department of Cardiology, Harvard Medical School, Boston, MA 02120, USA Bioabsorbable drug-eluting stents (BDES) offer multiple advantages over a permanent bare metal stent (BMS) for coronary artery disease (CAD). However, current BDES remains two major issues: inferior radial strength and biocompatibility. PowerStent ® Absorb BDES, fabricated by co-formulating amorphous calcium phosphate (ACP) nanoparticles with poly- L-lactic acid (PLLA/ACP, 98/2, w/w) and 2% Paclitaxel (PAX, w/w) was designed to address these issues. Two cohorts of 6 miniature pigs were each implanted with PLLA/PAX (control, 2% PAX, w/w) or PowerStent ® Absorb BDES. After 1 month in-vivo study, histological analyses showed significantly reduced restenosis in the PowerStent ® Absorb BDES cohort relative to the control cohort (4449 ± 1049% vs. 64.47 ± 16.2%, p< 005). Stent recoil (21.57 ± 5.36% vs. 33.81 ± 11.49, P< 005) and inflammation (3.01 ± 0.62 vs. 4.07 ± 0.86, P< 001) were also obviously decreased. From in-vitro studies, PLLA/ACP/PAX stent tube maintained significantly greater radial strength than control group during 6 months in-vitro degradation (PLLA/ACP/PAX vs. PLLA/PAX: before hydrolysis: 82.4 ± 1.9 N vs.74.8 ± 3.8 N; 6 weeks: 73.9 ± 1.8 N vs. 68.0 ± 5.3 N; 3 months: 73.5 ± 3.4 N vs.67.2 ± 3.8 N; 6 months: 56.3 ± 8.1 N vs. 57.5 ± 4.9 N). Moreover, ACP facilitated the hydrolytic degradation of PLLA compared with control one (62.6% vs. 49.8%), meanwhile, it also increased the crystallinity of PLLA (58.4% vs. 50.7%) at 6 months. From SEM observations, ACP created nanometer pores that enlarge gradually to a micrometer scale as degradation proceeds. The changes of the porosity may result in greatly promoting re-endothelialization. KEYWORDS: Biodegradable Drug-Eluting Stent (BDES), Amorphous Calcium Phosphate (ACP) Nanoparticles, Poly-L-Lactic Acid (PLLA), Porcine Coronary Artery Implantation, Radial Strength, Degradation, Biocompatibility. INTRODUCTION Coronary drug-eluting stents (DES) have been widely used in the treatment of coronary artery disease. At a clinical level, coronary arterial stents provide critical scaffolding ∗ Authors to whom correspondence should be addressed. Emails: tiangenwu@yahoo.com, xjjiang@whu.edu.cn † These three authors equally contributed to this work. Received: 5 November 2013 Accepted: 24 December 2013 support for up to six months post-procedure. Despite the prevalence of metal DES, there are significant drawbacks including the need for costly, long-term anti-platelet ther- apy, and retention of a permanent metal artifact in the vessel. 1–3 With the release of positive data from Abbott’s ABSORB trial, 4 a clinical consensus is building in favor of the commercialization of bioabsorbable drug-eluting stents (BDES). The key mechanical traits for candidate BDES materials and designs are predictable bio-degradation, 1194 J. Biomed. Nanotechnol. 2014, Vol. 10, No. 7 1550-7033/2014/10/1194/011 doi:10.1166/jbn.2014.1868