Wang Zuyong, Du Zheren, Chan Jerry Kok Yen, Teoh Swee Hin, Thian Eng San, Hong Minghui
Department of Mechanical Engineering, National University of Singapore, 9 Engineering Drive 1, Singapore 117576, Singapore.
Department of Electrical and Computer Engineering, National University of Singapore, 2 Engineering Drive 3, Singapore 117576, Singapore.
ACS Biomater Sci Eng. 2015 Dec 14;1(12):1239-1249. doi: 10.1021/acsbiomaterials.5b00455. Epub 2015 Nov 11.
Tissue architecture plays critical roles in the physiological functions of blood vessels. Surface-patterned films are promising to replicate cellular alignment as in the native vessels. However, for vascular tissue engineering (TE) applications, the current surface-patterned films lack structural support for the myoendothelial communications between tunica media and intima. Herein, we report the development of direct microperforation using a femtosecond laser on surface-patterned films for the native-like architecture reconstruction of blood vessels. Poly(ε-caprolactone) (PCL) thin films were surface-patterned with anisotropic microridges/grooves. Direct femtosecond laser ablation further resulted in microscale through-holes for the PCL films, without invasive thermal damage to the ridges/grooves on the nonprocessed surface. Laser fluence and pulse number were observed to significantly influence the microperforation on both hole quality and dimension. The PCL films after direct femtosecond laser microperforation exhibited improved flexible properties, without sacrificing the yield stress. Meanwhile, direct femtosecond laser microperforation resulted in PCL films with hydrophilic permeability to transport nutritional/signaling biomolecules and allowed for heterocellular protrusion ingrowth into the through-holes for physical myoendothelial contacts. Small-diameter vascular TE scaffolds based on the as-fabricated PCL films could enable a hybrid vascular wall construction with aligned stromal multilayers and a confluent endothelium similar to those of the native vascular tissue. These results showed that direct femtosecond laser microperforation could be a reliable approach for producing biomimetic films with through-holes. The developed vascular TE scaffolds with microridges/grooves and through-holes have the potential to offer structural support for vascular architecture reconstruction with the native-like stromal and endothelial components.
组织结构在血管的生理功能中起着关键作用。表面图案化薄膜有望复制天然血管中的细胞排列。然而,对于血管组织工程(TE)应用而言,当前的表面图案化薄膜缺乏对中膜和内膜之间肌内皮通讯的结构支持。在此,我们报道了使用飞秒激光在表面图案化薄膜上进行直接微穿孔,以实现血管的天然样结构重建。聚(ε-己内酯)(PCL)薄膜表面被图案化为具有各向异性的微脊/微槽。飞秒激光直接烧蚀进一步在PCL薄膜上形成了微米级的通孔,而对未处理表面上的脊/槽没有造成侵入性热损伤。观察到激光能量密度和脉冲数对微穿孔的孔质量和尺寸均有显著影响。飞秒激光直接微穿孔后的PCL薄膜表现出改善的柔韧性,同时不牺牲屈服应力。与此同时,飞秒激光直接微穿孔使PCL薄膜具有亲水性通透性,可运输营养/信号生物分子,并允许异细胞突起向内生长到通孔中,以实现物理性的肌内皮接触。基于所制备的PCL薄膜的小直径血管TE支架能够构建具有排列的基质多层结构和汇合内皮的混合血管壁,类似于天然血管组织。这些结果表明,飞秒激光直接微穿孔可能是一种制备具有通孔的仿生薄膜的可靠方法。所开发的具有微脊/微槽和通孔的血管TE支架有潜力为具有天然样基质和内皮成分的血管结构重建提供结构支持。