氨基酸配位自组装水凝胶的结构调控及抗菌性能研究

Antimicrobial hydrogel is one of the most important biomedical materials, which has been widely applied in wound dressings, tissue engineering, medical device coatings and so on. However, the reported antibacterial hydrogels could hardly combine the broad-spectrum antibacterial ability, biocompatibility, and injectability, which significantly reduced their clinical applications. In this project, we will design and synthesize antimicrobial amino acids, which can coordinated with metal ions. Then, we will use metal ions with broad-spectrum antibacterial activity to tune the self-assembly of the amino acids towards the fabrication of hydrogels suitable for antimicrobial agent delivery and release. Combined with the molecular simulations, the antibacterial mechanism behind the amino acids coordinated hydrogels against the bacteria will be unrevealed. The coordination interactions between the amino acids and metal ions not only can facilitate the in situ mineralization of metal nanoparticles with well-dispersion and precisely controlled size but also can tune the mechanical properties of the amino acids hydrogels. The interactions between the hydrogel and metal nanoparticles endows them the capability of retention and sustained release of amino acids and metal nanoparticles, which exhibits advantageous with the reduced drug dosage and toxicity yet improved biological availability. The outcomes of this project will not only improve our understanding on the biomimetic self-assembly based on the construction of biomolecular self-assembly systems combined with metal-coordinated interactions and biomineralization process, but also give new insights into the design and development of highly efficient antimicrobial agents and treatment strategy.

抗菌水凝胶作为一种重要的生物医用材料而广泛应用在伤口敷料、组织工程和医疗器械涂层等领域。然而目前已报道的抗菌水凝胶很难同时兼顾广谱抗菌、生物相容和可注射性，极大地限制了其临床应用。本项目拟设计、合成具有金属配位能力和抗菌性能的氨基酸组装基元，通过兼具抗菌性能的金属离子调控氨基酸配位自组装，构筑用于抗菌药物递送和释放的水凝胶，结合理论模拟，揭示氨基酸配位组装水凝胶的抗菌机制和规律。氨基酸与金属离子间的配位作用，不仅可实现原位矿化生成的金属纳米颗粒在氨基酸水凝胶中的可控分布和尺寸的精确调控，还可用于氨基酸水凝胶力学性能的调控。该抗菌水凝胶可实现抗菌氨基酸和金属纳米颗粒的保留和持续释放，从而具有降低药物使用量、降低药物毒性、提高生物利用度等优点。本项目的执行，不仅能通过金属离子调控生物分子组装和生物矿化增强对仿生自组装的认识和理解，还有望在抗菌治疗策略和抗菌药物新剂型的开发方面提供新思路。

抗菌水凝胶作为一种重要的生物医用材料而广泛应用在伤口敷料、组织工程和医疗器械涂层等领域。然而目前已报道的抗菌水凝胶很难同时兼顾广谱抗菌、生物相容和可注射性，极大地限制了其临床应用。针对上述难题，本项目设计并选取具有抗菌活性的氨基酸和金属离子为组装基元，通过对金属离子配位作用和氨基酸分子间弱相互作用的调控，结合原位矿化，实现了金属纳米颗粒在氨基酸水凝胶中的可控分布和尺寸的精确调控以及水凝胶力学性能的调控，进而构建了一系列生物安全、抗菌谱宽、力学性能可调的高效抗菌水凝胶，揭示了氨基酸配位组装水凝胶的抗菌机制和规律。该抗菌水凝胶可实现抗菌氨基酸和金属纳米颗粒的保留和持续释放，从而具有降低药物使用量、降低药物毒性、提高生物利用度等优点。更为重要的是，在本项目的执行过程中，我们发现氨基酸配位自组装过程中，会首先发生液-液相分离形成富含氨基酸-金属离子配合物的液滴，其作为亚稳态的成核前驱体引发了后续自组装纳米纤维的成核。该规律同样适用于氨基酸和肽的自组装以及共组装，从而提出了液-液相分离介导的超分子自组装多步成核新机制，回答了“成核点从何而来”这一关键科学问题。通过本项目的研究，一方面为抗菌治疗策略和抗菌药物新剂型的开发提供了有益探索；另一方面为超分子自组装的精准调控提供了新的启示和手段。本项目的研究成果发表学术论文 15 篇，包括 Nat. Rev. Chem. 1 篇，Angew. Chem. Int. Ed. 3篇， Adv. Mater. 1 篇， ACS Nano 3 篇， Small 1 篇。