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一种自修复水凝胶眼药水,可持续递送去整合素和金属蛋白酶 9(decorin),以预防角膜瘢痕形成。

A self-healing hydrogel eye drop for the sustained delivery of decorin to prevent corneal scarring.

机构信息

School of Chemical Engineering, University of Birmingham, Birmingham, BI5 2TT, UK; Dentistry, Warwick Medical School, University of Warwick, Coventry, CV4 7AL, UK.

School of Chemical Engineering, University of Birmingham, Birmingham, BI5 2TT, UK.

出版信息

Biomaterials. 2019 Jul;210:41-50. doi: 10.1016/j.biomaterials.2019.04.013. Epub 2019 Apr 20.

DOI:10.1016/j.biomaterials.2019.04.013
PMID:31055049
Abstract

Scarring/Opacity on the surface of the eye and vascularisation following infectious diseases, inflammation and corneal trauma are often a leading cause of blindness. The 'gold standard' treatment to prevent corneal scarring is the application of amniotic membrane (AM) to the ocular surface in the acute stage of injury. Although clinically effective, the use of the AM is associated with biological variability and unpredictable responses. Potential health risks including disease transmission, significant ethical issues surrounding the tissue donation process and stringent regulations/storage conditions, preclude widespread use. Consequently, there is a demand for the development of a new, synthetic alternative, that is stable at room temperature, capable of protecting the wound and has the capacity to deliver anti-scarring and anti-inflammatory mediators. Here we have developed a micro-structured fluid gel eye drop, to deliver a potent anti-scarring molecule, decorin. We have compared the release of decorin from the formulated dressing to a typical gel film, demonstrating enhanced release for the fluid gel eye-drops. Therefore, we have investigated the effect of the fluid gel system in 2D human corneal fibroblast culture models, as well as shown the retention of the gellan fluid gel in an in vivo rat model. At the same time the efficacy of the fluid gel eye drop was studied in an organ culture model, whereby the fluid gel containing decorin, significantly (P < 0.05) increased re-epithelialisation within 4 days of treatment.

摘要

眼部表面瘢痕/不透明和传染性疾病、炎症及角膜创伤后的血管化常常是失明的主要原因。防止角膜瘢痕形成的“金标准”治疗方法是在损伤的急性期将羊膜(AM)应用于眼表面。尽管在临床上有效,但 AM 的使用与生物变异性和不可预测的反应有关。包括疾病传播在内的潜在健康风险、围绕组织捐赠过程的重大伦理问题以及严格的法规/储存条件,排除了其广泛应用。因此,人们需要开发一种新的、稳定的、可在室温下储存、能够保护伤口且具有输送抗瘢痕和抗炎介质能力的合成替代品。在这里,我们开发了一种微结构的流体凝胶滴眼剂,以输送一种有效的抗瘢痕分子——decorin。我们比较了从配方敷料中释放的 decorin 与典型的凝胶膜的释放情况,证明了流体凝胶滴眼剂的释放增强。因此,我们研究了该流体凝胶系统在二维人角膜成纤维细胞培养模型中的作用,以及在体内大鼠模型中展示了 gellan 流体凝胶的保留情况。同时,还在器官培养模型中研究了流体凝胶滴眼剂的功效,其中含有 decorin 的流体凝胶在治疗后 4 天内显著(P<0.05)增加了再上皮化。

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