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

IF 5.2 2区 医学 Q1 PHARMACOLOGY & PHARMACY
Haowen Qi , Bingqing Wang , Mingjuan Wang , Haifeng Xie , Chen Chen
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Abstract

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.

Abstract Image

用于按需给药和增强体外成骨分化的 pH/ROS 响应型抗氧化和抗菌 GelMA 水凝胶
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,进一步加剧这种状况,降低局部 pH 值,对骨缺损愈合产生不利影响。传统的给药支架材料难以满足这种复杂多变的微环境的需求。本研究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给药。傅立叶变换红外光谱(FTIR)和 X 射线光电子能谱(XPS)证明了两种硼酸盐复合物与 GelMA 的共交联。硼酸盐复合物的加入改善了水凝胶的机械性能、溶胀率、降解动力学和抗氧化性能。水凝胶表现出 pH 值和 ROS 反应,并能协同控制药物释放。原花青素的释放可保护小鼠成骨细胞前体细胞免受氧化应激,并促进其成骨细胞分化。水凝胶能对 pH 值的变化做出反应,及时释放足够的阿米卡星,从而发挥高效的抗菌作用。总之,水凝胶递送系统在解决骨缺损中的感染和炎症问题以及促进早期骨愈合方面表现出了良好的前景。
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来源期刊
CiteScore
10.70
自引率
8.60%
发文量
951
审稿时长
72 days
期刊介绍: The International Journal of Pharmaceutics is the third most cited journal in the "Pharmacy & Pharmacology" category out of 366 journals, being the true home for pharmaceutical scientists concerned with the physical, chemical and biological properties of devices and delivery systems for drugs, vaccines and biologicals, including their design, manufacture and evaluation. This includes evaluation of the properties of drugs, excipients such as surfactants and polymers and novel materials. The journal has special sections on pharmaceutical nanotechnology and personalized medicines, and publishes research papers, reviews, commentaries and letters to the editor as well as special issues.
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