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

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 (R) 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 (R) Absorb BDES. After 1 month in-vivo study, histological analyses showed significantly reduced restenosis in the PowerStent (R) 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.