Juarez Alejandro, Djallali Mohamed, Piché Marilyse, Thériault Mathieu, Groleau Marc, Beroual Sharifa, McTiernan Christopher D, Lin Grace, Hélie Pierre, Carrier Michel, Griffith May, Brunette Isabelle
Department of Ophthalmology, Université de Montréal, Montreal, QC, Canada.
Centre Universitaire d'Ophtalmologie de l'Université de Montréal à l'Hôpital Maisonneuve-Rosemont, Montreal, QC, Canada.
Front Bioeng Biotechnol. 2021 Dec 15;9:773294. doi: 10.3389/fbioe.2021.773294. eCollection 2021.
To evaluate long-term functionality of corneas regenerated using a cell-free, liquid hydrogel filler (LiQD Cornea) after deep corneal trauma in the feline model. Two healthy cats underwent 4 mm diameter stepwise 250/450 µm deep surgical corneal ablation with and without needle perforation. The filler comprising 10% (w/w) collagen-like peptide conjugated to polyethylene glycol (CLP-PEG) and 1% fibrinogen and crosslinked with 2% (w/w) 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMTMM), was applied to the wound bed previously coated with thrombin (250 U/ml). gelation occurred within 5 min, and a temporary tarsorrhaphy was performed. Eyes were examined weekly for 1 month, then monthly over 12 months. Outcome parameters included slit-lamp, Scheimpflug tomography, optical coherence tomography, confocal and specular microscopy, and immunohistochemistry studies. The gelled filler was seamlessly incorporated, supporting smooth corneal re-epithelialization. Progressive in-growth of keratocytes and nerves into the filler corresponding to the mild haze observed faded with time. The regenerated neo-cornea remained stably integrated throughout the 12 months, without swelling, inflammation, infection, neovascularization, or rejection. The surrounding host stroma and endothelium remained normal at all times. Tomography confirmed restoration of a smooth surface curvature. Biointegration of this hydrogel filler allowed stable restoration of corneal shape and transparency in the feline model, with less inflammation and no neovascularization compared to previous reports in the minipig and rabbit models. It offers a promising alternative to cyanoacrylate glue and corneal transplantation for ulcerated and traumatized corneas in human patients.
为评估在猫模型中使用无细胞液体水凝胶填充物(LiQD角膜)修复深层角膜创伤后角膜的长期功能。两只健康的猫接受了直径4毫米、深度为250/450微米的逐步手术角膜消融,有或没有针刺穿孔。将由10%(w/w)与聚乙二醇共轭的胶原样肽(CLP-PEG)和1%纤维蛋白原组成并与2%(w/w)4-(4,6-二甲氧基-1,3,5-三嗪-2-基)-4-甲基吗啉氯化物(DMTMM)交联的填充物应用于预先涂有凝血酶(250 U/ml)的伤口床。凝胶在5分钟内形成,并进行了临时睑裂缝合。每周检查眼睛1个月,然后在12个月内每月检查一次。结果参数包括裂隙灯检查、Scheimpflug断层扫描、光学相干断层扫描、共聚焦和镜面显微镜检查以及免疫组织化学研究。凝胶化的填充物无缝整合,支持角膜平滑地重新上皮化。随着时间的推移,角膜细胞和神经逐渐向填充物内生长,与观察到的轻度混浊相对应,混浊逐渐消退。再生的新角膜在12个月内一直保持稳定整合,没有肿胀、炎症、感染、新生血管或排斥反应。周围的宿主基质和内皮始终保持正常。断层扫描证实恢复了平滑的表面曲率。这种水凝胶填充物的生物整合使得猫模型中的角膜形状和透明度得以稳定恢复,与之前在小型猪和兔模型中的报道相比,炎症更少且无新生血管。它为人类患者溃疡和创伤角膜的治疗提供了一种有望替代氰基丙烯酸酯胶水和角膜移植的方法。