Department of Dermatology, The First Affiliated Hospital of Jinan University and Jinan University Institute of Dermatology, Guangzhou 510630, China; Department of Materials Science and Engineering, Jinan University, Guangzhou 510632, China; Engineering Research Center of Artificial Organs and Materials, Ministry of Education, Guangzhou 510632, China.
Department of Materials Science and Engineering, Jinan University, Guangzhou 510632, China; Engineering Research Center of Artificial Organs and Materials, Ministry of Education, Guangzhou 510632, China.
Int J Biol Macromol. 2024 Jun;270(Pt 2):132387. doi: 10.1016/j.ijbiomac.2024.132387. Epub 2024 May 15.
Alginate (SA) comprises repeating unis of β-1, 4 linked β-D-mannuronic acid (M) and α-L-guloronic acid (G) in varying proportions. The M/G ratio greatly impacts its anti-inflammatory properties in tissue healing wound, as less knowledge reported. This study examined the performances of both SA and SA hydrogel crosslinked with copper ions (SA-Cu) with different M/G ratios are studied. SA with higher M/G ratios stimulated macrophage migration and shifted from M0 to the pro-inflammatory Ml phenotype, while lower M/G ratios shifted from M1 to the pro-repair M2 phenotype. Furthermore, SA-Cu hydrogels with lower M/G ratios exhibited enhanced cross-linking degree, mechanical and rheological properties, as well Cu releasing rate. The reason may be attributed to a relative easy binding between Cu ions and G unit among Cu ions, M unit and G unit. In vitro cell evaluation showed that SA-Cu hydrogel with M/G ratio of 1:1 activated M2 macrophages and up-regulated anti-inflammatory cytokines expression more effectively than those of SA-Cu ratios (2:1) and (1:2). In vivo, SA-Cu hydrogel with M/G ratio of 1:1 expedited diabetic wound healing, accelerating infiltration and phenotype shift of M2 macrophages, and enhancing anti-inflammatory factors, epithelialization and collagen deposition in healing phases. This research highlights the significant role of M/G ratios in SA materials in influencing macrophage behavior and inflammatory responses, which would benefit its application field.
藻酸盐（SA）由β-1,4 连接的β-D-甘露糖醛酸（M）和α-L-古洛糖醛酸（G）的重复单元组成，其比例变化很大。M/G 比对组织愈合伤口的抗炎特性影响很大，但目前报道的知识较少。本研究考察了不同 M/G 比的 SA 和铜离子交联的 SA 水凝胶（SA-Cu）的性能。具有较高 M/G 比的 SA 刺激巨噬细胞迁移，并从 M0 向促炎 M1 表型转变，而较低的 M/G 比则从 M1 向促修复 M2 表型转变。此外，具有较低 M/G 比的 SA-Cu 水凝胶表现出增强的交联度、机械和流变性能以及更高的 Cu 释放速率。原因可能归因于 Cu 离子与 G 单元之间、Cu 离子与 M 单元和 G 单元之间相对容易结合。体外细胞评价表明，M/G 比为 1:1 的 SA-Cu 水凝胶比 M/G 比为 2:1 和 1:2 的 SA-Cu 水凝胶更有效地激活 M2 巨噬细胞并上调抗炎细胞因子的表达。体内研究表明，M/G 比为 1:1 的 SA-Cu 水凝胶加速糖尿病伤口愈合，加速 M2 巨噬细胞的浸润和表型转变，并增强愈合阶段的抗炎因子、上皮化和胶原沉积。这项研究强调了 M/G 比对影响巨噬细胞行为和炎症反应的 SA 材料的重要作用，这将有益于其应用领域。
