Biomedical Materials Group, Institute of Pharmacy , Martin Luther University Halle-Wittenberg , Heinrich Damerow Strasse 4 , 06120 Halle (Saale) , Germany.
Interdisciplinary Center of Material Research , Martin Luther University Halle-Wittenberg , Heinrich Damerow Strasse 4 , 06120 Halle (Saale) , Germany.
ACS Appl Mater Interfaces. 2018 Mar 14;10(10):8507-8518. doi: 10.1021/acsami.7b19022. Epub 2018 Feb 28.
Control of the biomaterial properties through stimuli-responsive polymeric platforms has become an essential technique in recent biomedical applications. A multilayer system of thiolated chitosan (t-Chi) and thiolated chondroitin sulfate (t-CS), consisting of five double layers ([t-Chi/t-CS]), was fabricated here by applying a layer-by-layer coating strategy. To represent a novel class of chemically tunable nanostructures, the ability to cross-link pendant thiol groups was tested by a rise from pH 4 during layer formation to pH 9.3 and a more powerful chemical stimulus by using chloramine-T (ChT). Following both treatments, the resulting multilayers showed stimuli-dependent behavior, as demonstrated by their content of free thiols, wettability, surface charge, elastic modulus, roughness, topography, thickness, and binding of fibronectin. Studies with human dermal fibroblasts further demonstrated the favorable potential of the ChT-responsive multilayers as a cell-adhesive surface compared to pH-induced cross-linking. Because the [t-Chi/t-CS] multilayer system is responsive to stimuli such as the pH and redox environment, multilayer systems with disulfide bond formation may help to tailor their interaction with cells, film degradation, and controlled release of bioactive substances like growth factors in a stimuli-responsive manner useful in future wound healing and tissue engineering applications.
通过刺激响应性聚合物平台来控制生物材料特性已成为最近生物医学应用中的一项重要技术。本文通过层层涂层策略制备了由五层[巯基化壳聚糖（t-Chi）/巯基化硫酸软骨素（t-CS）]组成的硫醇化壳聚糖（t-Chi）和硫醇化硫酸软骨素（t-CS）的多层体系。为了代表一类新型的化学可调纳米结构，通过在层形成过程中从 pH4 升高到 pH9.3 以及使用氯胺-T（ChT）进行更强大的化学刺激来测试连接悬垂硫醇基团的能力。两种处理后，所得多层膜表现出刺激响应行为，如自由硫醇含量、润湿性、表面电荷、弹性模量、粗糙度、形貌、厚度以及纤连蛋白结合等。与 pH 诱导交联相比，用人类真皮成纤维细胞进行的研究进一步证明了 ChT 响应性多层膜作为细胞黏附表面的良好潜力。由于[t-Chi/t-CS]多层体系对 pH 和氧化还原环境等刺激敏感，因此具有二硫键形成的多层体系可能有助于以刺激响应的方式调节其与细胞的相互作用、薄膜降解以及生物活性物质（如生长因子）的控制释放，这在未来的伤口愈合和组织工程应用中非常有用。
