Zhang Shutao, Yang Hongtao, Wang Minqi, Mantovani Diego, Yang Ke, Witte Frank, Tan Lili, Yue Bing, Qu Xinhua
Department of Bone and Joint Surgery, Department of Orthopedics, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200001, China.
School of Engineering Medicine, Beihang University, Beijing 100191, China.
Innovation (Camb). 2023 Aug 28;4(6):100503. doi: 10.1016/j.xinn.2023.100503. eCollection 2023 Nov 13.
Bacterial infectious diseases are one of the leading causes of death worldwide. Even with the use of multiple antibiotic treatment strategies, 4.95 million people died from drug-resistant bacterial infections in 2019. By 2050, the number of deaths will reach 10 million annually. The increasing mortality may be partly due to bacterial heterogeneity in the infection microenvironment, such as drug-resistant bacteria, biofilms, persister cells, intracellular bacteria, and small colony variants. In addition, the complexity of the immune microenvironment at different stages of infection makes biomaterials with direct antimicrobial activity unsatisfactory for the long-term treatment of chronic bacterial infections. The increasing mortality may be partly attributed to the biomaterials failing to modulate the active antimicrobial action of immune cells. Therefore, there is an urgent need for effective alternatives to treat bacterial infections. Accordingly, the development of immunomodulatory antimicrobial biomaterials has recently received considerable interest; however, a comprehensive review of their research progress is lacking. In this review, we focus mainly on the research progress and future perspectives of immunomodulatory antimicrobial biomaterials used at different stages of infection. First, we describe the characteristics of the immune microenvironment in the acute and chronic phases of bacterial infections. Then, we highlight the immunomodulatory strategies for antimicrobial biomaterials at different stages of infection and their corresponding advantages and disadvantages. Moreover, we discuss biomaterial-mediated bacterial vaccines' potential applications and challenges for activating innate and adaptive immune memory. This review will serve as a reference for future studies to develop next-generation immunomodulatory biomaterials and accelerate their translation into clinical practice.
细菌感染性疾病是全球主要死因之一。即便采用多种抗生素治疗策略，2019年仍有495万人死于耐药细菌感染。到2050年，每年死亡人数将达1000万。死亡率上升可能部分归因于感染微环境中的细菌异质性，如耐药菌、生物膜、持留菌、胞内菌和小菌落变异体。此外，感染不同阶段免疫微环境的复杂性使得具有直接抗菌活性的生物材料在慢性细菌感染的长期治疗中效果不佳。死亡率上升可能部分归因于生物材料未能调节免疫细胞的主动抗菌作用。因此，迫切需要有效的替代方法来治疗细菌感染。相应地，免疫调节抗菌生物材料的研发近来备受关注；然而，目前缺乏对其研究进展的全面综述。在本综述中，我们主要聚焦于感染不同阶段使用的免疫调节抗菌生物材料的研究进展及未来展望。首先，我们描述细菌感染急性期和慢性期免疫微环境的特征。然后，我们重点介绍抗菌生物材料在感染不同阶段的免疫调节策略及其相应优缺点。此外，我们讨论生物材料介导的细菌疫苗在激活先天性和适应性免疫记忆方面的潜在应用及挑战。本综述将为未来开发下一代免疫调节生物材料并加速其转化为临床应用的研究提供参考。
