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促血管生成的光交联丝素水凝胶:一种修复肺泡骨缺损的潜在候选材料。

Pro-angiogenic photo-crosslinked silk fibroin hydrogel: a potential candidate for repairing alveolar bone defects.

机构信息

Foshan University, Foshan Stomatology Hospital & School of Medicine, Foshan, China.

出版信息

J Appl Oral Sci. 2023 Aug 28;31:e20230158. doi: 10.1590/1678-7757-2023-0158. eCollection 2023.

Abstract

OBJECTIVE

This study aimed to develop a pro-angiogenic hydrogel with in situ gelation ability for alveolar bone defects repair.

METHODOLOGY

Silk fibroin was chemically modified by Glycidyl Methacrylate (GMA), which was evaluated by proton nuclear magnetic resonance (1H-NMR). Then, the photo-crosslinking ability of the modified silk fibroin was assessed. Scratch and transwell-based migration assays were conducted to investigate the effect of the photo-crosslinked silk fibroin hydrogel on the migration of human umbilical vein endothelial cells (HUVECs). In vitro angiogenesis was conducted to examine whether the photo-crosslinked silk fibroin hydrogel would affect the tube formation ability of HUVECs. Finally, subcutaneous implantation experiments were conducted to further examine the pro-angiogenic ability of the photo-crosslinked silk fibroin hydrogel, in which the CD31 and α-smooth muscle actin (α-SMA) were stained to assess neovascularization. The tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were also stained to evaluate inflammatory responses after implantation.

RESULTS

GMA successfully modified the silk fibroin, which we verified by our 1H-NMR and in vitro photo-crosslinking experiment. Scratch and transwell-based migration assays proved that the photo-crosslinked silk fibroin hydrogel promoted HUVEC migration. The hydrogel also enhanced the tube formation of HUVECs in similar rates to Matrigel®. After subcutaneous implantation in rats for one week, the hydrogel enhanced neovascularization without triggering inflammatory responses.

CONCLUSION

This study found that photo-crosslinked silk fibroin hydrogel showed pro-angiogenic and inflammation inhibitory abilities. Its photo-crosslinking ability makes it suitable for matching irregular alveolar bone defects. Thus, the photo-crosslinkable silk fibroin-derived hydrogel is a potential candidate for constructing scaffolds for alveolar bone regeneration.

摘要

目的

本研究旨在开发一种具有原位凝胶化能力的促血管生成水凝胶,用于牙槽骨缺损修复。

方法

丝素蛋白通过甲基丙烯酸缩水甘油酯(GMA)进行化学修饰,通过质子核磁共振(1H-NMR)进行评估。然后,评估修饰丝素蛋白的光交联能力。划痕和 Transwell 迁移实验用于研究光交联丝素蛋白水凝胶对人脐静脉内皮细胞(HUVEC)迁移的影响。体外血管生成实验用于研究光交联丝素蛋白水凝胶是否会影响 HUVEC 的管形成能力。最后,进行皮下植入实验以进一步研究光交联丝素蛋白水凝胶的促血管生成能力,其中通过染色 CD31 和 α-平滑肌肌动蛋白(α-SMA)来评估新生血管形成。还对植入后炎症反应进行了肿瘤坏死因子-α(TNF-α)和白细胞介素-1β(IL-1β)染色。

结果

GMA 成功修饰了丝素蛋白,我们通过 1H-NMR 和体外光交联实验进行了验证。划痕和 Transwell 迁移实验证明光交联丝素蛋白水凝胶促进了 HUVEC 的迁移。水凝胶还以类似于 Matrigel®的速度增强了 HUVEC 的管形成。在大鼠皮下植入一周后,水凝胶增强了血管生成,而没有引发炎症反应。

结论

本研究发现光交联丝素蛋白水凝胶具有促血管生成和抑制炎症的能力。其光交联能力使其适合匹配不规则的牙槽骨缺损。因此,光交联丝素蛋白衍生的水凝胶是构建牙槽骨再生支架的潜在候选物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/66e8/10501750/6e4ffeb2165e/1678-7765-jaos-31-e20230158-gf01.jpg

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