【作者】 高玉洁；

【导师】 朱锦涛； 张连斌；

【作者基本信息】 华中科技大学 ， 高分子化学与物理， 2021， 博士

【摘要】 细菌感染严重影响人们的身体健康和生活质量,情况严重时还可能危及生命。细菌检测和细菌感染的治疗是防治细菌性传染病、保护人类生命健康、降低国家公共卫生支出的重要方面。因此,发展高效、便捷、低成本的细菌检测和抗菌策略具有重要意义。其中,水凝胶材料可结合丰富的组分和功能,具有优异的可设计性,在细菌检测和抗菌方面具有广阔应用前景。尤其是,将光功能组分复合于水凝胶材料中,可得到利用光识别细菌或治疗细菌感染的光功能复合水凝胶。这些光功能复合水凝胶在细菌检测与治疗中具有可视化输出、时间-空间可控、远程非接触等独特优势,近年来得到了广泛关注。尽管如此,用于细菌检测和抗菌的光功能复合水凝胶仍存在一些挑战与不足:（1）现有用于细菌检测的光功能复合水凝胶往往需要配备额外的激发设备或特定的信号输出设备,不利于便捷的直接检测;（2）在用于治疗细菌感染的光动力抗菌中,光敏材料的激发光利用率较低,影响了光动力抗菌的效率;在光热抗菌过程中,局部高温可能对正常组织造成损伤。针对上述问题,本论文通过对光功能复合水凝胶的功能组分的理性化设计与结构调控,利用引入光子晶体结构、筛选优化光功能组分、构筑响应性水凝胶基体等策略,制备了一系列具有可视化细菌检测或光学抗菌能力的光功能复合水凝胶。本论文主要研究内容如下:（1）通过磁场诱导碳包覆的四氧化三铁纳米粒子自组装和丙烯酰胺、N,N’-亚甲基双丙烯酰胺以及甲基丙烯酰化明胶的原位光聚合,制备了具有鲜艳结构色的明胶基光子晶体复合水凝胶。光子晶体复合水凝胶中的明胶组分可被明胶酶或铜绿假单胞菌代谢物水解,从而促进光子晶体复合水凝胶产生结构色变化（其色彩可由绿到红）,实现对铜绿假单胞菌的可视化检测。（2）在自组装的二氧化硅纳米粒子阵列中,通过紫外光引发交联聚（乙二醇）苯基醚丙烯酸酯,制备了光子晶体复合水凝胶。利用光子晶体的慢光子效应和胶体粒子的多重散射效应,提高沉积在光子晶体复合水凝胶表面的、具有匹配吸收的光敏剂/光催化剂的光利用率以及在活性氧产生能力。相比于纯水凝胶,光子晶体复合水凝胶使光敏剂在光辐照下的活性氧产生能力提高至2.7倍,抗菌比例最高增加～38.7%,实现高效光动力抗菌。（3）利用仿生矿化和离子交换过程获得海藻酸-Mn O₂-Ag₃PO₄复合物,将其与Ca Cl₂溶液混合制备了物理交联的海藻酸钙-Mn O₂-Ag₃PO₄复合水凝胶。这种复合水凝胶在模拟太阳光辐照下,可同时实现光热转换以及活性氧的产生。复合水凝胶的光热效应提高了细菌细胞膜的通透性,从而增强了活性氧对细菌的杀伤。此外,该复合水凝胶在感染猪皮模型中表现出优异的原位抗菌效果。（4）在聚多巴胺、聚乙烯亚胺以及还原氧化石墨烯存在下,通过紫外光引发的丙烯酰胺和N,N’-亚甲基双丙烯酰胺的原位光聚合,制备了自粘附光热抗菌水凝胶。通过调节多巴胺和还原氧化石墨烯的掺杂量,实现了水凝胶的粘附、光热和力学性能的调控。在模拟太阳光辐照下,水凝胶的抗菌比例最高增加～30.6%。此外,该水凝胶在光辐照下可局部加热小鼠皮肤伤口,使伤口愈合速率提高～16.1%。更多还原

【Abstract】 Bacterial infections seriously affect health and quality of life and even endanger lives in some critical conditions.The detection and treatment of bacterial infections are important aspects to prevent and control bacterial infectious diseases,to protect health and lives,and to reduce national public health expenditures.It is of great significance to develop efficient and inexpensive strategies for bacterial detection and inhibition.Hydrogels have excellent designability by combining different components and functions and have been demonstrated promising in bacterial detection and antibacterial purpose.In particular,optically functional composite hydrogels,which incorporate optically functional components in the hydrogels,have been recently developed for bacterial detection and inhibition.These optically functional composite hydrogels can identify or treat bacterial infections based on light,which have the advantages of visual output,high spatial and temporal precision,and noncontact.However,there are still some challenges:（1）the existing optically functional composite hydrogels used for bacterial detection always need to be equipped with specific equipment for excitation and signal output,which is not suitable for direct detection.（2）In the process of photodynamic therapy（PDT）,ineffective utilization of excitation light hinders the effects of PDT.Besides,to improve the photothermal therapy（PTT）effect,a high local temperature is required,which may cause damages to normal tissues.In this thesis,through the rational design and structural control of the functional components of the optically functional composite hydrogels,by introducing photonic crystals,optimizing optically functional components,and constructing responsive hydrogels,etc.,a series of optically functional composite hydrogels with the capabilities of self-reporting or light-triggered bacterial inhibition were obtained by in-situ photopolymerization or physically cross-linking.The main research contents of this thesis are as follows:（1）Gelatin-based photonic composite hydrogels with bright structural colors were prepared by the self-assembly of carbon-coated Fe₃O₄ nanoparticles under magnetic field and in-situ photopolymerization of acrylamide,N,N’-methylenebis-（acrylamide）,and gelatin methacrylate.The color of the photonic composite hydrogels changed from green to red due to the specific hydrolysis of gelatin triggered by gelatinase or the metabolite of Pseudomonas aeruginosa（P.aeruginosa）,which can be applied to detect P.aeruginosa.（2）Photonic composite hydrogels were obtained by UV light-initiated crosslinking of poly（ethylene glycol）phenyl ether acrylate with the self-assembled Si O₂ nanoparticles colloidal array.Photonic composite hydrogels can prompt the photosensitizers or photocatalysts with matched absorption,which were deposited on the surface of the photonic composite hydrogel,to generate more reactive oxygen species（ROS）based on the slow photon phenomenon of photonic crystals and multiple scattering effects of the colloidal nanoparticles.Compared with pure hydrogels,photonic composite hydrogels greatly enhanced the production of ROS to 2.7 times,and the antibacterial ratio increased by 38.7%under light irradiation,realizing effective photodynamic antibacterial.（3）Alginate-Mn O₂-Ag₃PO₄ complex was prepared via a biomimetic mineralization and ion exchange process.The calcium alginate-Mn O₂-Ag₃PO₄ composite hydrogels were obtained by the physically cross-linking of calcium ions.The photothermal conversion and the generation of ROS can be achieved under simulated solar light irradiation.The photothermal effect of the composite hydrogel enhanced the bacterial membrane permeability,further increasing the antibacterial effect of ROS.Besides,the in-situ antibacterial effect of the composite hydrogels in the infected skins model was demonstrated.（4）Self-adhesive photothermal antibacterial hydrogels were prepared by UV light-initiated in-situ photopolymerization of acrylamide and N,N’-methylenebis-（acrylamide）in the presence of polydopamine,polyethyleneimine,and reduced graphene oxide（r GO）.Through adjusting the contents of dopamine and r GO,the adhesion,photothermal,and mechanical properties of the hydrogels were optimized.Furthermore,with the assistance of solar light,the antibacterial activity of the hydrogels increased by 30.6%,and the cutaneous wound repair accelerated by 16.1%due to the localized heat around the wound.更多还原