丝绸
巨噬细胞
外体
重编程
化学
代谢活性
功能(生物学)
细胞生物学
自愈水凝胶
微泡
医学
生物化学
生物
材料科学
细胞
高分子化学
小RNA
体外
复合材料
基因
生理学
作者
Jiale Jin,Yiqi Yang,Jian Yang,Zeyu Sun,Dongyu Wang,Yifang Qin,Chong‐Yu Ruan,Dongdong Li,Yi Pan,Jiangdong Wu,Qian Zhang,Yihe Hu,Pengfei Lei
标识
DOI:10.1016/j.ijbiomac.2024.134830
摘要
Diabetic infected bone defects (DIBD) with abnormal immune metabolism are cline to the hard-to-treat bacterial infections and delayed bone regeneration, which present significant challenges in clinic. Control of immune metabolism is believed to be important in regulating fundamental immunological processes. Here, we developed a macrophage metabolic reprogramming hydrogel composed of modified silk fibroin (Silk-6) and poly-l-lysine (ε-PL) and further integrated with M2 Macrophage-derived Exo (M2-Exo), named as Silk-6/ε-PL@Exo. This degradable hydrogel showed a broad-spectrum antibacterial performance towards both Gram-positive and -negative bacteria. More importantly, the release of M2-Exo from Silk-6/ε-PL@Exo could target M1 macrophages, modulating the activity of the key enzyme hexokinase II (HK2) to control the inflammation-related NF-κB pathway, alleviate lactate accumulation, and inhibit glycolysis to normalize the cycle, thereby promoting M1-to-M2 balance. Using a rat model of DIBD, Silk-6/ε-PL@Exo hydrogel promoted infection control, balanced immune responses and accelerated the bone defect healing. Overall, this study demonstrates that this Silk-6/ε-PL @Exo is a promising filler biomaterials with multi-function to treat DIBD and emphasizes the importance of metabolic reprogramming in bone regeneration.
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