A biomaterial-based therapy for lower limb ischemia using Sr/Si bioactive hydrogel that inhibits skeletal muscle necrosis and enhances angiogenesis.
A biomaterial-based therapy for lower limb ischemia using Sr/Si bioactive hydrogel that inhibits skeletal muscle necrosis and enhances angiogenesis.
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DOI：
10.1016/j.bioactmat.2023.02.027
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发表时间：
2023-08
影响因子：
18.9
通讯作者：
Wang, Lixin
中科院分区：
文献类型：
--
作者：
Yuan, Ye;Zhang, Zhaowenbin;Mo, Fandi;Yang, Chen;Jiao, Yiren;Wang, Enci;Zhang, Yuchong;Lin, Peng;Hu, Chengkai;Fu, Weiguo;Chang, Jiang;Wang, Lixin
关键词：
肌肉坏死和血管生成是治疗下肢缺血性疾病的两大难题。本研究设计了一种同时具有促进血管生成、调节炎症和抑制肌肉坏死的三功能锶/硅生物陶瓷/海藻酸盐复合水凝胶，用于治疗肢体缺血性疾病。特别是利用海藻酸钠、硅酸钙和碳酸锶制备了可注射水凝胶，并在10分钟内成胶。更重要的是，这种复合水凝胶在28天内持续释放生物活性的锶和二氧化硅−离子。水凝胶释放的生物活性离子在体外对人脐静脉内皮细胞、血管内皮细胞、C2C12细胞和RAW 264.7细胞的生物活性进行了验证，并通过C57BL/6小鼠股动脉结扎模型证实了水凝胶的治疗作用。结果表明，复合水凝胶促进了血管生成，形成了新的侧支毛细血管，重建了血供。此外，生物活性水凝胶直接促进肌肉调节因子(MyoG和MyoD)的表达，保护骨骼肌免受坏死，抑制M1极化，促进巨噬细胞M2极化，减轻炎症，从而保护骨骼肌细胞，间接促进血管形成。我们的结果表明，这些生物陶瓷/藻酸盐复合生物活性水凝胶是治疗肢体缺血的有效生物材料，提示基于生物材料的方法在治疗缺血性疾病方面可能具有显着的潜力。设计了一种新型的含锶/硅生物陶瓷/藻酸盐复合水凝胶，用于治疗肢体缺血性疾病。SA/Sr/Si可释放生物活性的Sr2+和SiO32−离子，协同刺激血管生成。Sa/sr/Si直接促进肌肉调节因子的表达，从而保护骨骼肌免于坏死。SA/Sr/Si抑制巨噬细胞M1极化，促进M2极化，从而减轻炎症反应。
Muscle necrosis and angiogenesis are two major challenges in the treatment of lower-limb ischemic diseases. In this study, a triple-functional Sr/Si-containing bioceramic/alginate composite hydrogel with simultaneous bioactivity in enhancing angiogenesis, regulating inflammation, and inhibiting muscle necrosis was designed to treat lower-limb ischemic diseases. In particular, sodium alginate, calcium silicate and strontium carbonate were used to prepare injectable hydrogels, which was gelled within 10 min. More importantly, this composite hydrogel sustainedly releases bioactive Sr2+ and SiO32− ions within 28 days. The biological activity of the bioactive ions released from the hydrogels was verified on HUVECs, SMCs, C2C12 and Raw 264.7 cells in vitro, and the therapeutic effect of the hydrogel was confirmed using C57BL/6 mouse model of femoral artery ligation in vivo. The results showed that the composite hydrogel stimulated angiogenesis, developed new collateral capillaries, and re-established the blood supply. In addition, the bioactive hydrogel directly promoted the expression of muscle-regulating factors (MyoG and MyoD) to protect skeletal muscle from necrosis, inhibited M1 polarization, and promoted M2 polarization of macrophages to reduce inflammation, thereby protecting skeletal muscle cells and indirectly promoting vascularization. Our results indicate that these bioceramic/alginate composite bioactive hydrogels are effective biomaterials for treating hindlimb ischemia and suggest that biomaterial-based approaches may have remarkable potential in treating ischemic diseases. A novel Sr/Si-containing bioceramic/alginate composite hydrogel was designed to treat lower limb ischemic diseases. SA/Sr/Si release bioactive Sr2+ and SiO32− ions to synergistically stimulate angiogenesis. SA/Sr/Si directly promotes the expression of muscle regulating factors to protect skeletal muscle from necrosis. SA/Sr/Si inhibits M1 polarization and promotes M2 polarization of macrophages to reduce inflammatory reaction.
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影响因子：
4.1
作者：
Morandi F;Croce M;Cangemi G;Barco S;Rigo V;Carlini B;Amoroso L;Pistoia V;Ferrini S;Corrias MV
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