<br>pH/ROS 响应性抗氧化和抗菌 GelMA 水凝胶，用于按需药物输送和增强体外成骨分化,International Journal of Pharmaceutics

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pH/ROS 响应性抗氧化和抗菌 GelMA 水凝胶，用于按需药物输送和增强体外成骨分化
International Journal of Pharmaceutics ( IF 5.3 ) Pub Date : 2024-04-20 , DOI: 10.1016/j.ijpharm.2024.124134
Haowen Qi ₁ , Bingqing Wang ₁ , Mingjuan Wang ₂ , Haifeng Xie ₁ , Chen Chen ₂

Affiliation

长期炎症，包括细菌感染引起的炎症，会导致活性氧（ROS）过度积累，进一步加重病情，降低局部pH值，并对骨缺损愈合产生不利影响。传统的药物输送支架材料难以满足这种复杂且动态的微环境的需求。在这项工作中，基于硼酸盐复合物独特的 pH 和 ROS 响应性，合成了一种智能明胶甲基丙烯酰 (GelMA) 水凝胶，用于原花青素和阿米卡星的双重递送。傅里叶变换红外光谱 (FTIR) 和 X 射线光电子能谱 (XPS) 证明了两种硼酸酯配合物与 GelMA 的共交联。硼酸盐配合物的添加改善了水凝胶的机械性能、溶胀比、降解动力学和抗氧化性能。水凝胶表现出 pH 和 ROS 响应以及对药物释放的协同控制。原花青素被响应性释放，以保护小鼠成骨细胞前体细胞免受氧化应激并促进其成骨分化。该水凝胶响应pH变化并及时释放足够的阿米卡星，从而发挥高效的抗菌作用。总体而言，水凝胶输送系统在解决骨缺损的感染和炎症问题以及促进早期骨愈合方面表现出一种有前景的策略。

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A pH/ROS-responsive antioxidative and antimicrobial GelMA hydrogel for on-demand drug delivery and enhanced osteogenic differentiation in vitro

Long-term inflammation, including those induced by bacterial infections, contributes to the superfluous accumulation of reactive oxygen species (ROS), further aggravating this condition, decreasing the local pH, and adversely affecting bone defect healing. Conventional drug delivery scaffold materials struggle to meet the demands of this complex and dynamic microenvironment. In this work, a smart gelatin methacryloyl (GelMA) hydrogel was synthesized for the dual delivery of proanthocyanidin and amikacin based on the unique pH and ROS responsiveness of boronate complexes. Fourier-transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) demonstrated the co-crosslinking of two boronate complexes with GelMA. The addition of the boronate complexes improved the mechanical properties, swelling ratio, degradation kinetics and antioxidative properties of the hydrogel. The hydrogel exhibited pH and ROS responses and a synergistic control over the drug release. Proanthocyanidin was responsively released to protect mouse osteoblast precursor cells from oxidative stress and promote their osteogenic differentiation. The hydrogel responded to pH changes and released sufficient amikacin in a timely manner, thereby exerting an efficient antimicrobial effect. Overall, the hydrogel delivery system exhibited a promising strategy for solving infectious and inflammatory problems in bone defects and promoting early-stage bone healing.

更新日期：2024-04-20

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