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.

6-Month Follow-Up of a Novel Biodegradable Drug-Eluting Stent Composed of Poly-L-Lactic Acid and Amorphous Calcium Phosphate Nanoparticles in Porcine Coronary Artery

“…The stent also maintains an adequate stent radial strength with an acceptable stent recoil, limited restenosis formation, positive vessel remodeling and high biocompatibility. These findings are in agreement with our previously published 1-month follow-up data 19 and demonstrate the sustained performance of the stent throughout a longer follow-up period.…”

“…As discussed in our previous report, 19 ACP plays an essential role in the reduced inflammatory response, the favorable biocompatibility and the positive vessel remodeling of the PowerStent ® Absorb stents. Two mechanisms may explain these beneficial effects.…”

“…19 Briefly, the extruded tube of the stent (3.0 mm diameter × 13 mm length × 150 um width) is laser-automated with the stent surface and struts coated with a layer of paclitaxel blended in the biodegradable carrier PLGA (∼20 m thick). 17 21 Paclitaxel is released from the surface coating over the first 30 post implantation days (fast release) and from the stent struts during the course of the stent degradation (slow and low dosage release) which can be up to one year.…”

“…[14][15][16][17][18] Our most recent study in porcine coronary artery also demonstrated that the stent had increased structural stability and excellent antirestenotic property one month post-implantation. 19 In the present study, we further evaluate this novel biodegradable DES with respect to the radial strength, biocompatibility and functionality in a porcine model of coronary artery stenting with 6-month follow-up results available.…”

Antibacterial PHAs coating for titanium implants

“…Synthetic polyesters, poly(lactic acid) (PLA), poly(glycolic acid) (PGA) and their copolymers, polycaprolactone (PCL), poly(lactic-co-glycolic acid) (PLGA) are examples of biodegradable polymers used for DDS [4,5]. Lately, natural polyesters polyhydroxyalkanoates (PHAs) emerged as a vast family of potential candidates as biodegradable polymers for DDS.…”