Department of Orthopedics Trauma and Microsurgery, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China.
Key Laboratory of Biomedical Polymers of Ministry of Education & Department of Chemistry, Wuhan University, Wuhan, 430072, China.
Adv Mater. 2024 Nov;36(44):e2408473. doi: 10.1002/adma.202408473. Epub 2024 Aug 30.
Treatment of osteomyelitis is clinically challenging with low therapeutic efficacy and high risk of recurrence owing to the immunosuppressive microenvironment. Existing therapies are limited by drug concentration and single regulatory effect on the immune network, and emphasize the role of anti-inflammatory effects in reducing osteoclast rather than the role of proinflammatory effects in accelerating infection clearance, which is not conducive to complete bacteria elimination and recurrence prevention. Herein, a direct-current triboelectric nanogenerator (DC-TENG) is established to perform antibacterial effects and modulate immunological properties of infectious microenvironments of osteomyelitis through electrical stimulation, namely triboelectric immunotherapy. Seeing from the results, the triboelectric immunotherapy successfully activates polarization to proinflammatory (M1) macrophages in vitro, accompanied by satisfying direct antibacterial effects. The antibacterial and osteogenic abilities of triboelectric immunotherapy are verified in rat cranial osteomyelitis models. The effects on the polarization and differentiation of immune-related cells in vivo are investigated by establishing in situ tibial osteomyelitis models and immunosurveillance models in C57 mice respectively, indicating the ability of activating immunity and producing immunological memory for in situ infection and secondary recurrence, thus accelerating healing and preventing relapse. This study provides an efficient, long-acting, multifunctional, and wearable triboelectric immunotherapy strategy for drug-free osteomyelitis treatment systems.
骨髓炎的治疗具有临床挑战性,由于免疫抑制微环境,其治疗效果低,复发风险高。现有的治疗方法受到药物浓度和对免疫网络的单一调节作用的限制,强调抗炎作用在减少破骨细胞方面的作用,而不是促炎作用在加速感染清除方面的作用,这不利于完全消除细菌和预防复发。在此,建立了直流摩擦纳米发电机(DC-TENG),通过电刺激实现抗感染微环境的抗菌作用和调节免疫特性,即摩擦电免疫治疗。从结果来看,摩擦电免疫治疗成功地激活了体外极化向促炎(M1)巨噬细胞,并具有令人满意的直接抗菌作用。摩擦电免疫治疗在大鼠颅骨骨髓炎模型中验证了其抗菌和成骨能力。通过建立原位胫骨骨髓炎模型和 C57 小鼠免疫监测模型,研究了其对体内免疫相关细胞极化和分化的影响,表明其具有激活免疫和产生针对原位感染和二次复发的免疫记忆的能力,从而加速愈合和预防复发。本研究为无药物骨髓炎治疗系统提供了一种高效、长效、多功能和可穿戴的摩擦电免疫治疗策略。