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牛血清白蛋白(BSA)配制水凝胶在角膜伤口愈合和上皮细胞再生中的治疗效果:一项体外研究。

Therapeutic efficacy of BSA formulated hydrogels in corneal wound healing and epithelial cell regeneration: an ex vivo study.

作者信息

Samivel Ramachandran, Alanazi Mana A, Khan Adnan A, Masmali Ali M, Alanazi Saud A, Almubrad Turki, Akhtar Saeed

机构信息

Cornea Research Chair, Department of Optometry, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia.

College of Applied Medical Sciences, Inaya Medical Sciences, Riyadh, Saudi Arabia.

出版信息

Sci Rep. 2025 Jun 6;15(1):19956. doi: 10.1038/s41598-025-04408-3.

Abstract

Corneal injury requires both epithelial regeneration and stromal repair, and formulated biomaterials established to repair damaged corneas can be used in regenerative medicine. The challenge is to ensure that biomaterials can be incorporated into the host tissue and delivered intracellularly without causing rapid material deprivation, thus maintaining corneal transparency. Bovine serum albumin-formulated hydrogels (BHG) were prepared by dissolving with riboflavin, retinoic acid, and 2.5% glutaraldehyde solutions. Periphery-centered wounds from camel corneas (8mm diameter and 250 µm depth) were mounted on a dome-shaped agarose gel in six-well plates containing BHG-supplemented serum-free Medium 199. The plates were then incubated at 37 °C for 24, 48, and 72 h. A complete set of corneoscleral rings was procured and processed for histopathological, electron microscopy, and immunohistochemistry assays. Histological and electron microscopy results showed that all epithelial layers and anterior stroma developed faster in the BHG-treated wounds than in the untreated wounded corneas. Compared to untreated wounded corneas, BHG-treated corneas accumulated higher levels of fibronectin and ki-67 and lower levels of alpha-smooth muscle actin inductions. BHG-treated corneal wounds healed faster than untreated wounded corneas. Overall, BHG enhances epithelial regeneration and strengthens the stromal architecture by upregulating ECM and growth factors. Hence, BHG is a promising therapeutic hydrogel for wounded corneas, and further studies on corneal stromal wound healing and epithelial cell reimbursement in an in vivo model are required.

摘要

角膜损伤需要上皮再生和基质修复,用于修复受损角膜的定制生物材料可用于再生医学。挑战在于确保生物材料能够融入宿主组织并在细胞内递送,同时不会导致材料快速耗尽,从而维持角膜透明度。通过将牛血清白蛋白与核黄素、视黄酸和2.5%戊二醛溶液溶解来制备牛血清白蛋白配方水凝胶(BHG)。将骆驼角膜的周边中心伤口(直径8mm,深度250µm)置于含有补充了BHG的无血清培养基199的六孔板中的穹顶形琼脂糖凝胶上。然后将平板在37°C下孵育24、48和72小时。获取一整套角膜巩膜环并进行组织病理学、电子显微镜和免疫组织化学分析。组织学和电子显微镜结果表明,与未处理的受伤角膜相比,BHG处理的伤口中所有上皮层和前基质的发育速度更快。与未处理的受伤角膜相比,BHG处理的角膜中纤连蛋白和ki-67的积累水平更高,α-平滑肌肌动蛋白诱导水平更低。BHG处理的角膜伤口比未处理的受伤角膜愈合得更快。总体而言,BHG通过上调细胞外基质和生长因子来促进上皮再生并加强基质结构。因此,BHG是一种有前景的用于受伤角膜的治疗性水凝胶,需要在体内模型中对角膜基质伤口愈合和上皮细胞补充进行进一步研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63f1/12144276/fb67edbd7a02/41598_2025_4408_Fig1_HTML.jpg

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