Division of Chemistry and Chemical Engineering, California Institute of Technology, 1200 E California Blvd, Pasadena CA, 91125, USA.
Division of Chemistry and Chemical Engineering, California Institute of Technology, 1200 E California Blvd, Pasadena CA, 91125, USA; Division of Sustainable Materials, ENEA Centro Ricerche Portici, Piazzale E. Fermi 1, Portici, 80055, Italy.
Acta Biomater. 2022 Jan 15;138:313-326. doi: 10.1016/j.actbio.2021.11.005. Epub 2021 Nov 17.
Treatment of vascular disease, from peripheral ischemia to coronary heart disease (CHD), is poised for transformation with the introduction of transient implants designed to "scaffold" regeneration of blood vessels and ultimately leave nothing behind. Improved materials could expand the use of these devices. Here, we examine one of the leading polymers for bioresorbable scaffolds (BRS), polylactide (PLA), as the matrix of nanocomposites with tungsten disulfide (WS) nanotubes (WSNT), which may provide mechanical reinforcement and enhance radio-opacity. We evaluate in vitro cytotoxicity using vascular cells, flow-induced crystallization and radio-opacity of PLA-WSNT nanocomposites at low WSNT concentration. A small amount of WSNT (0.1 wt%) can effectively promote oriented crystallization of PLA without compromising molecular weight. And radio-opacity improves significantly: as little as 0.5 to 1 wt% WSNT doubles the radio-opacity of PLA-WSNT relative to PLA at 17 keV. The results suggest that a single component, WSNT, has the potential to increase the strength of BRS to enable thinner devices and increase radio-opacity to improve intraoperative visualization. The in vitro toxicity results indicate that PLA-WSNT nanocomposites are worthy of investigation in vivo. Although substantial further preclinical studies are needed, PLA-WSNT nanocomposites may provide a complement of material properties that may improve BRS and expand the range of lesions that can be treated using transient implants. STATEMENT OF SIGNIFICANCE: Bioresorbable Scaffolds (BRSs) support regeneration of arteries without permanent mechanical constraint. Poly-L-lactide (PLLA) is the structural material of the first approved BRS for coronary heart disease (ABSORB BVS), withdrawn due to adverse events in years 1-3. Here, we examine tungsten disulfide (WS) nanotubes (WSNT) in PLA to address two contributors to early complications: (1) reinforce PLLA (enable thinner BRS), and (2) increase radiopacity (provide intraoperative visibility). For BRS, it is significant that WSNT disperse, remain dispersed, reduce friction and improve mechanical properties without additional chemicals or surface modifications. Like WS nanospheres, bare WSNT and PLA-WSNT nanocomposites show low cytotoxicity in vitro. PLA-WSNT show enhanced flow-induced crystallization relative to PLA, motivating future study of the processing behavior and strength of these materials.
血管疾病的治疗,从外周缺血到冠心病 (CHD),随着旨在“支架”血管再生的瞬态植入物的引入,正处于转型之中,最终不会留下任何痕迹。改进的材料可以扩大这些设备的使用范围。在这里,我们研究了生物可吸收支架 (BRS) 的一种领先聚合物聚乳酸 (PLA) 作为二硫化钨 (WS) 纳米管 (WSNT) 的纳米复合材料的基质,WSNT 可能提供机械增强并提高放射密度。我们使用血管细胞评估体外细胞毒性,评估 PLA-WSNT 纳米复合材料在低 WSNT 浓度下的流动诱导结晶和放射密度。少量的 WSNT(0.1wt%)可以有效地促进 PLA 的定向结晶,而不会降低分子量。放射密度显著提高:仅 0.5 至 1wt% WSNT 就可以使 PLA-WSNT 的放射密度相对于 PLA 提高一倍,在 17keV 时提高一倍。结果表明,单个成分 WSNT 有可能提高 BRS 的强度,使设备更薄,并提高放射密度,以改善术中可视化。体外毒性结果表明,PLA-WSNT 纳米复合材料值得进一步进行体内研究。尽管还需要进行大量的临床前研究,但 PLA-WSNT 纳米复合材料可能会提供一系列材料性能的补充,这些性能可能会改善 BRS 并扩大使用瞬态植入物治疗的病变范围。意义声明:生物可吸收支架 (BRS) 支持动脉的再生而不会产生永久的机械约束。聚 L-乳酸 (PLLA) 是第一种用于治疗冠心病 (ABSORB BVS) 的批准的 BRS 的结构材料,由于在 1-3 年内出现不良事件而被撤回。在这里,我们研究了二硫化钨 (WS) 纳米管 (WSNT) 在 PLA 中的应用,以解决两个导致早期并发症的因素:(1)增强 PLLA(使 BRS 更薄),(2)增加放射密度(提供术中可见度)。对于 BRS 而言,重要的是 WSNT 分散、保持分散、降低摩擦并改善机械性能,而无需额外的化学物质或表面改性。与 WS 纳米球一样,裸露的 WSNT 和 PLA-WSNT 纳米复合材料在体外显示出低细胞毒性。PLA-WSNT 显示出比 PLA 更高的流动诱导结晶度,这激发了对这些材料的加工行为和强度的进一步研究。