title: 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.
abstract: 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 +/- 410.49% 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.
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Lan
authors.forename: Yongnan
authors.initials: Y
authors.lastname: Lyu
authors.forename: Jianmin
authors.initials: J
authors.lastname: Xiao
authors.forename: Xiaoxin
authors.initials: X
authors.lastname: Zheng
authors.forename: Suyuan
authors.initials: S
authors.lastname: He
authors.forename: Gaoke
authors.initials: G
authors.lastname: Feng
authors.forename: Yipei
authors.initials: Y
authors.lastname: Zhang
authors.forename: Shihang
authors.initials: S
authors.lastname: Wang
authors.forename: Edward
authors.initials: E
authors.lastname: Kislauskis
authors.forename: Jiuhao
authors.initials: J
authors.lastname: Chen
authors.forename: Stephen
authors.initials: S
authors.lastname: McCarthy
authors.forename: Roger
authors.initials: R
authors.lastname: Laham
authors.forename: Xuejun
authors.initials: X
authors.lastname: Jiang
authors.forename: Tim
authors.initials: T
authors.lastname: Wu
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry*; D002130:Calcium Phosphates / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D003324:Coronary Artery Disease / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy*; D003331:Coronary Vessels / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D054855:Drug-Eluting Stents; D005260:Female; D019344:Lactic Acid / Q000737:chemistry*; D008297:Male; D008422:Materials Testing; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D017239:Paclitaxel / Q000494:pharmacology; D011091:Polyesters; D011108:Polymers / Q000737:chemistry*; D011859:Radiography; D013552:Swine; D013556:Swine, Miniature
chemical_list: D001672:Biocompatible Materials; D002130:Calcium Phosphates; D011091:Polyesters; D011108:Polymers; C519480:amorphous calcium phosphate; D019344:Lactic Acid; C033616:poly(lactide); D017239:Paclitaxel