壳聚糖基柔性导电抗菌敷料的构建及其在电刺激促进慢性伤口愈合中的应用

Chronic wounds and the accompanied infections have become one of the major threats to public health. Electrical stimulation (ES) has emerged as a useful tool to promote the healing of chronic wounds. However, for the current ES strategy, ES is applied by electrodes placed around the wound, making it difficult to stimulate the entire wound region. In addition, application of ES alone cannot effectively treat infected wounds. To overcome these limitations, we plan to develop a new ES strategy using chitosan-based conductive and anti-bacterial flexible dressing. Compared with the conventional electrode-based ES strategy, the conductive and flexible dressing would closely fit and fully cover the wound, and the applied ES through the dressing can stimulate the whole wound region to accelerate the healing. The applied electrical signals may also act synergistically with the anti-bacterial agents in the dressing to disrupt the pathological bacteria in the biofilm formed on the wound. In this project, we will investigate the effect of the structures and content of the incorporated conductive polymers and anti-bacterial agents on the physicochemical properties of the dressing. The structure and composition of the dressing as well as the ES parameters will be optimized according to the in vitro cellular and bacterial evaluation. Furthermore, in vivo assay will be conducted to test the effectiveness of the ES strategy on the chitosan-based conductive and anti-bacterial flexible dressing, paving the way to develop a new ES therapy for chronic wounds.

慢性伤口及其伴随的感染已成为一个亟待解决的严重的公共卫生问题。电刺激能有效促进慢性伤口愈合，但目前的电刺激治疗方案主要通过放置于伤口附近的电极施加电刺激，电信号难以覆盖整个伤口区域，且难以有效治疗伤口感染。针对上述不足，我们拟设计一套基于壳聚糖基柔性导电抗菌敷料的电刺激方案，与传统的电极刺激方案相比，导电的柔性敷料能与伤口紧密贴合，使通过敷料传导的电信号能刺激整个伤口区域，加速伤口愈合。此外，施加的电信号有望与敷料中的抗菌组分协同作用以治疗伤口感染。在本项目中，我们将研究引入的导电聚合物与抗菌组分对敷料性能的影响，并通过体外细胞、细菌评价优化敷料的设计及电刺激方案。在此基础上，采用动物实验验证此方案对感染性慢性伤口的治疗效果，为开发针对慢性伤口的新型治疗手段提供理论和实验基础。

慢性伤口及其伴随的感染已成为一个亟待解决的严重的公共卫生问题。电刺激能有效促进慢性伤口愈合，但目前的电刺激治疗方案主要通过放置于伤口附近的电极施加电刺激，电信号难以覆盖整个伤口区域，且难以有效治疗伤口感染。针对上述不足，我们设计合成了一系列基于壳聚糖的柔性导电抗菌水凝胶，并将其作为电刺激的载体，对慢性伤口进行电刺激。与传统的电极刺激方案相比，导电水凝胶不仅能作为敷料使用，紧密贴合伤口进行保护，还能通过水凝胶传导电信号刺激整个伤口区域，加速伤口愈合。外部施加的电信号还能与敷料中的抗菌组分协同作用以治疗伤口感染。我们系统研究了各组分对水凝胶敷料力学性能、导电性能、生物相容性和抗菌性能的影响，并通过体外细胞的活性和增殖实验、体外抗菌实验等优化水凝胶的设计及电刺激方案。我们发现优化后的电刺激方案能显著促进成纤维细胞和内皮细胞的增殖与迁移，同时电刺激与抗菌导电敷料会产生协同抗菌作用。之后，利用糖尿病大鼠模型，验证了电刺激与柔性导电抗菌敷料联用，能有效治疗感染性慢性伤口。在此基础上，我们对研发的导电水凝胶体系进行拓展，设计合成了以具有壳聚糖类似结构的海藻酸盐作为基础的导电水凝胶，降低了蛋白吸附，降低换药对伤口产生的可能的二次伤害。为了提升水凝胶的导电性同时避免因小分子掺杂剂流失引起的导电性下降，我们开发了基于大分子掺杂剂的原位掺杂技术，并将其应用到水凝胶的制备中。因此，本项目的实施为开发针对慢性伤口的新型治疗手段提供了理论和实验基础。