郭婉婷, 贾学丽, 胡亚丹, 王可, 刘岩, 金义光. 治疗放烧复合伤合并细菌感染的3D打印蛭弧菌水凝胶J. 药学学报, 2025, 60(5): 1262-1271. DOI: 10.16438/j.0513-4870.2024-1258
引用本文: 郭婉婷, 贾学丽, 胡亚丹, 王可, 刘岩, 金义光. 治疗放烧复合伤合并细菌感染的3D打印蛭弧菌水凝胶J. 药学学报, 2025, 60(5): 1262-1271. DOI: 10.16438/j.0513-4870.2024-1258
GUO Wan-ting, JIA Xue-li, HU Ya-dan, WANG Ke, LIU Yan, JIN Yi-guang. 3D-printed Bdellovibrio bacteriovorus hydrogel for treatment of infected combined radiation and burn injuryJ. Acta Pharmaceutica Sinica, 2025, 60(5): 1262-1271. DOI: 10.16438/j.0513-4870.2024-1258
Citation: GUO Wan-ting, JIA Xue-li, HU Ya-dan, WANG Ke, LIU Yan, JIN Yi-guang. 3D-printed Bdellovibrio bacteriovorus hydrogel for treatment of infected combined radiation and burn injuryJ. Acta Pharmaceutica Sinica, 2025, 60(5): 1262-1271. DOI: 10.16438/j.0513-4870.2024-1258

治疗放烧复合伤合并细菌感染的3D打印蛭弧菌水凝胶

3D-printed Bdellovibrio bacteriovorus hydrogel for treatment of infected combined radiation and burn injury

  • 摘要: 电离辐射损伤和皮肤烧伤同时或相继发生可导致放烧复合伤(combined radiation and burn injury, CRBI)。放烧复合伤发生后机体免疫力降低, 易引起耐药细菌感染, 伤口难以愈合。蛭弧菌及其类似物(Bdellovibrio-and-like organisms, BALO) 是天然掠食性细菌, 能进入大多数革兰阴性菌周质空间, 降解宿主细胞内生物大分子。本研究以明胶、海藻酸钙和活化后的蛭弧菌悬液作为生物墨水, 利用3D打印技术制备蛭弧菌水凝胶(three dimensional-printed BALO-loaded hydrogel, TDBG), 用于皮肤CRBI合并耐药鲍曼不动杆菌(multidrug-resistant Acinetobacter baumannii, MRAB) 感染的治疗。3D打印水凝胶冻干后呈三维网状结构, 内部附着明胶薄膜, 具有良好的可打印性和生物黏附性。可打印性使其能根据伤口形状进行适应性打印, 为感染伤口提供个性化治疗; 三维网络结构能为蛭弧菌的生存和游动提供条件, 利于发挥高效掠食活性。所有动物实验经军事科学院军事医学研究院批准且实验均按照相关指导原则和规定进行(批准号: IACUC-DWZX-2022-834)。经TDBG治疗后, CRBI合并MRAB感染小鼠伤口闭合速率加快, 伤口部位炎性细胞因子表达水平降低, 胶原沉积增加, 伤口修复效果好。本研究拓宽了活体生物药的应用范围, 为其研发和临床应用提供参考。

     

    Abstract: Combined radiation and burn injury (CRBI) is induced by simultaneous or sequential ionizing radiation damage and skin burns. CRBI weakens the immune ability, leading to drug-resistant bacterial infections and delayed wound healing. Bdellovibrio-and-like organisms (BALO) are naturally predatory bacterium that can prey on most Gram-negative bacteria by entering the periplasmic space of their prey and degrading the biomolecules of host cells. In this study, we combined gelatin, calcium alginate, and activated BALO water samples to form bio-inks to three-dimensional (3D)-print BALO-loaded hydrogels (TDBG) for the treatment of CRBI combined with multidrug-resistant Acinetobacter baumannii (MRAB) infection. The freeze-dried 3D-printed hydrogel exhibited a 3D network structure attached with gelatin films, and owned good printability and biocompatibility. The printability improved adaptation to wound shapes for the personalized treatment of infected wounds. The 3D network structure allowed the surviving and motion of BALO, favoring its high predatory activity. All animal experiments were approved by the Ethics Committee of Academy of Military Medical Sciences, and the experiments were conducted in accordance with relevant guidelines and regulations (approval number: IACUC-DWZX-2022-834). TDBG treatment improved wound healing by accelerating the mouse wound closure rate of CRBI combined with MRAB infection, reducing the expression of pro-inflammatory cytokines in the wound tissues, and increasing collagen deposition. This study expands the application scope of live biological products and provides a basis for their development and clinical applications.

     

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