Abstract:
Infection is the most common complication after orthopedic surgery and can result in prolonged ailments such as chronic wounds, enlarged bone defects, and osteomyelitis. Iron, which is essential for bacterial metabolism and immune cell functions, is extremely important. Bacteria harness iron from nearby cells to promote biofilm formation, ensuring their survival. Iron deficiency within the infection microenvironment (IME) consequently hampers macrophage function, enabling further dissemination of the infection and hindering macrophage polarization to the M2 phenotype. Therefore, a novel approach is proposed to regulate macrophage polarization, aiming to restore the inflammatory immune environment. A composite hydrogel derived from natural polymers is developed to address infections and manage iron metabolism in macrophages. This IME-responsive hydrogel, named FCL-ECMH, is synthesized by encapsulating vermiculite functional core layers within a decellularized extracellular matrix hydrogel. It is noteworthy that FCL-ECMH can produce reactive oxygen species within the IME. Supplementary photothermal treatment enhances bacterial iron uptake, leading to ferroptosis-like death. This process also rejuvenates the iron-enriched macrophages around the IME, thereby enhancing their antibacterial and tissue repair functions. In vivo experiments confirmed the antibacterial and repair-promoting capabilities of FCL-ECMH, indicating its potential for clinical applications.
摘要:
感染是骨科手术后最常见的并发症,可导致长期的疾病,如慢性伤口,骨缺损扩大,骨髓炎。熨斗,这对细菌代谢和免疫细胞功能至关重要,是极其重要的。细菌利用附近细胞的铁来促进生物膜的形成,确保他们的生存。感染微环境(IME)内的铁缺乏因此阻碍巨噬细胞功能,使感染进一步传播并阻碍巨噬细胞向M2表型的极化。因此,提出了一种调节巨噬细胞极化的新方法,旨在恢复炎症免疫环境。开发了源自天然聚合物的复合水凝胶以解决感染并管理巨噬细胞中的铁代谢。这种IME响应水凝胶,名为FCL-ECMH,通过将蛭石功能核心层封装在脱细胞细胞外基质水凝胶中合成。值得注意的是,FCL-ECMH可以在IME内产生活性氧。补充光热处理增强细菌铁吸收,导致铁性死亡.这个过程也使IME周围的富含铁的巨噬细胞恢复活力,从而增强其抗菌和组织修复功能。体内实验证实了FCL-ECMH的抗菌和修复促进能力,表明其临床应用的潜力。