Two-stage degradation and novel functional endothelium characteristics of a 3-D printed bioresorbable scaffold

Abstract

Bioresorbable scaffolds have emerged as a new generation of vascular implants for the treatment of atherosclerosis, and designed to provide a temporary scaffold that is subsequently absorbed by blood vessels over time. Presently, there is insufficient data on the biological and mechanical responses of blood vessels accompanied by bioresorbable scaffolds (BRS) degradation. Therefore, it is necessary to investigate the inflexion point of degradation, the response of blood vessels, and the pathophysiological process of vascular, as results of such studies will be of great value for the design of next generation of BRS. In this study, abdominal aortas of SD rats were received 3-D printed poly- l -actide vascular scaffolds (PLS) for various durations up to 12 months. The response of PLS implanted aorta went through two distinct processes: (1) the neointima with desirable barrier function was obtained in 1 month, accompanied with slow degradation, inflammation, and intimal hyperplasia; (2) significant degradation occurred from 6 months, accompanied with decreasing inflammation and intimal hyperplasia, while the extracellular matrix recovered to normal vessels which indicate the positive remodeling. These in vivo results indicate that 6 months is a key turning point. This “two-stage degradation and vascular characteristics” is proposed to elucidate the long-term effects of PLS on vascular repair and demonstrated the potential of PLS in promoting endothelium function and positive remodeling, which highlights the benefits of PLS and shed some light in the future researches, such as drug combination coatings design.

Crosstalk between arterial components and bioresorbable, 3-D printed poly-l-lactic acid scaffolds

“…Based on the procedure followed in our previous study, 23 surface images were obtained at 1 and 6 months. The scaffold surface was rougher and more granular at 1 month and cruder at 6 months in the rat abdominal aorta, compared to the rabbit carotid artery (In Fig.…”

“…PLSs (∅ 2.0 × 12 mm, strut thickness 150 μm) manufactured using a proprietary 3-D printing technology 23,27 were kindly gifted by Beijing Ahmet Company; the detailed printing and testing processes were shown in our recently published paper. 21 Sprague-Dawley (SD) rats and New Zealand rabbits were purchased from the Animal Experimental Center of Daping Hospital and studies on animals were approved by the Animal Experiment Ethics Committee and Authority for Animal Protection of Chongqing University.…”

“…[20][21][22] In our previous study, we utilized 3-D printed PLLA endovascular scaffolds developed by Beijing Advanced Medical Technologies (AMT) that exhibited good mechanical properties when compared to those from Xinsorb, BVS, and DESolve, and better endothelial recovery when compared to that of BMSs in rats. 23 In addition, the results of a previous study involving the use of a 3-D printed AMsorb™ BRS (AMT) in porcine animals showed that complete reendothelialization could be achieved within 90 days with no thrombus formation. 24 Furthermore, the first AMsorb™ clinical trial is going on in China (Approval No.…”

The endothelium permeability after bioresorbable scaffolds implantation caused by the heterogeneous expression of tight junction proteins

“…Stent implantation objects commonly used for research include human, rat, rabbit, monkey, dog and so on. After PLLA scaffolds were implanted into the abdominal aorta of rats, vascular repair involved two processes, “0–6 months” (characterized by inflammation, neointimal hyperplasia, and endothelial re-functionalization) and “after 6 months” (characterized by scaffold degradation and positive vascular remodeling) [ 32 ]. After PLLA scaffolds were implanted into the coronary artery of pigs, some scaffold struts were still visible after 3 years, and the complete scaffold struts could not be observed by optical coherence tomography until 4 years later [ 41 ].…”

“…Each time point after scaffolds implantation/balloon injury, with 1 ​mL of solution containing 2% Evans blue dye (Solarbio, CAS: 314-13-6) via tail vein injection by standard procedures as previously described [ 32 ]. The arteries containing the scaffold were harvested 1 ​h after the dyeing cycle, and the heart was perfused with 0.9% heparinized saline.…”