研究动态
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具有促血管生成能力的光交联丝素纤维蛋白水凝胶:修复肺泡骨缺损的潜在候选物。

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

发表日期:2023
作者: Siyuan Wu, Xuezhong Zhou, Yilong Ai
来源: Bone & Joint Journal

摘要:

本研究旨在开发一种具有原位凝胶化能力的促血管生成的水凝胶,用于修复肺泡骨缺损。我们以丝素纤维蛋白通过丙烯酸甲醇酯(GMA)进行化学修饰,并通过质子核磁共振(1H-NMR)进行评估。然后,评估了修饰的丝素纤维蛋白的光交联能力。通过刮痕和透过性迁移实验来研究光交联丝素纤维蛋白水凝胶对人脐静脉内皮细胞(HUVEC)迁移的影响。通过体外血管生成实验来检验光交联丝素纤维蛋白水凝胶是否会影响HUVEC的管状结构形成能力。最后,进行皮下植入实验来进一步研究光交联丝素纤维蛋白水凝胶的促血管生成能力,其中CD31和α-平滑肌肌动蛋白(α-SMA)被染色以评估新生血管形成。肿瘤坏死因子-α (TNF-α)和白细胞介素-1β (IL-1β)也被染色以评估植入后的炎症反应。GMA成功修饰了丝素纤维蛋白,我们通过1H-NMR和体外光交联实验证实。刮痕和透过性迁移实验证明光交联丝素纤维蛋白水凝胶促进了HUVEC的迁移。该水凝胶还以与Matrigel相似的速率增强了HUVEC的管状结构形成。在大鼠皮下植入一周后,该水凝胶促进了新生血管形成,且不引发炎症反应。本研究发现,光交联丝素纤维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用于匹配不规则的肺泡骨缺损。因此,可光交联的丝素纤维蛋白衍生水凝胶是构建肺泡骨再生支架的潜在候选。
This study aimed to develop a pro-angiogenic hydrogel with in situ gelation ability for alveolar bone defects repair.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.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.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.