Kyle Daniel J T, Oikonomou Antonios, Hill Ernie, Vijayaraghavan Aravind, Bayat Ardeshir
Plastic and Reconstructive Surgery Research, Manchester Institute of Biotechnology, The University of Manchester, Manchester, UK. School of Computer Science, Centre for Mesoscience and Nanotechnology, The University of Manchester, Manchester, UK.
Bioinspir Biomim. 2016 Jul 25;11(4):046009. doi: 10.1088/1748-3190/11/4/046009.
Natural surface topographies are often self-similar with hierarchical features at the micro and nanoscale, which may be mimicked to overcome modern tissue engineering and biomaterial design limitations. Specifically, a cell's microenvironment within the human body contains highly optimised, fractal topographical cues, which directs precise cell behaviour. However, recreating biomimetic, fractal topographies in vitro is not a trivial process and a number of fabrication methods have been proposed but often fail to precisely control the spatial resolution of features at different lengths scales and hence, to provide true biomimetic properties. Here, we propose a method of accurately reproducing the self-similar, micro and nanoscale topography of a human biological tissue into a synthetic polymer through an innovative fabrication process. The biological tissue surface was characterised using atomic force microscopy (AFM) to obtain spatial data in X, Y and Z, which was converted into a grayscale 'digital photomask'. As a result of maskless grayscale optical lithography followed by modified deep reactive ion etching and replica molding, we were able to accurately reproduce the fractal topography of acellular dermal matrix (ADM) into polydimethylsiloxane (PDMS). Characterisation using AFM at three different length scales revealed that the nano and micro-topographical features, in addition to the fractal dimension, of native ADM were reproduced in PDMS. In conclusion, it has been shown that the fractal topography of biological surfaces can be mimicked in synthetic materials using the novel fabrication process outlined, which may be applied to significantly enhance medical device biocompatibility and performance.
天然表面形貌通常具有自相似性，在微观和纳米尺度上具有层次特征，可通过模仿这些特征来克服现代组织工程和生物材料设计的局限性。具体而言，人体细胞的微环境包含高度优化的分形地形线索，这些线索引导着精确的细胞行为。然而，在体外重现仿生分形形貌并非易事，虽然已经提出了多种制造方法，但这些方法往往无法精确控制不同长度尺度特征的空间分辨率，因此无法提供真正的仿生特性。在此，我们提出一种方法，通过创新的制造工艺，将人类生物组织的自相似微观和纳米尺度形貌精确复制到合成聚合物中。使用原子力显微镜（AFM）对生物组织表面进行表征，以获取X、Y和Z方向的空间数据，并将其转换为灰度“数字光掩模”。通过无掩模灰度光刻，随后进行改进的深反应离子蚀刻和复制成型，我们能够将无细胞真皮基质（ADM）的分形形貌精确复制到聚二甲基硅氧烷（PDMS）中。在三个不同长度尺度上使用AFM进行表征，结果表明，除了分形维数外，天然ADM的纳米和微观地形特征也在PDMS中得到了复制。总之，研究表明，利用所述的新型制造工艺，可以在合成材料中模仿生物表面的分形形貌，这可能会显著提高医疗设备的生物相容性和性能。
