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OcuPair,一种新型的可光交联聚酰胺-胺树形聚合物-透明质酸水凝胶绷带/角膜损伤及临时角膜修复用生物黏附剂。

OcuPair, a Novel Photo-crosslinkable PAMAM Dendrimer-Hyaluronic Acid Hydrogel Bandage/Bioadhesive for Corneal Injuries and Temporary Corneal Repair.

作者信息

Kambhampati Siva P, Sharma Rishi, Lin Hui, Appiani Santiago, Cleland Jeffrey L, Yiu Samuel C, Kannan Rangaramanujam M

机构信息

Center for Nanomedicine, Wilmer Eye Institute, Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Ashvattha Therapeutics, Inc., Baltimore, MD, USA.

出版信息

Adv Sci (Weinh). 2025 Jun;12(23):e2417731. doi: 10.1002/advs.202417731. Epub 2025 Mar 27.

Abstract

Traumatic corneal injuries are a leading cause of blindness among military personnel. These injuries need immediate attention in the combat zone, but treatment options are limited as life-saving measures are often prioritized. To address this critical gap, we have developed OcuPair, a two-component hydrogel system that consists of i) an injectable viscoelastic filler that stabilizes the ocular cavity and prevents hypotony. ii) An in situ photo-curable adhesive hydrogel comprising of methacrylated, hydroxyl PAMAM dendrimer and hyaluronic acid engineered to form a transparent, flexible, and robust bandage within 90 seconds, adhering to the corneal surface and ensuring a water-tight seal securing full-thickness corneal wounds. Ex vivo studies demonstrated that the adhesive hydrogel is mechanically robust and withstands intraocular pressures beyond physiological range. In a rabbit corneal injury model, OcuPair effectively sealed complex full-thickness wounds and preserved the eye with favorable clinical outcomes for 5 days with no toxicity over 30 days. In this study, we have validated the pilot scale synthesis, formulation optimization, GMP scale-up, and IDE-enabling GLP toxicity, essential for clinical translation as a battlefield-ready solution.

摘要

创伤性角膜损伤是军事人员失明的主要原因。这些损伤在战区需要立即得到关注,但由于通常优先采取救生措施,治疗选择有限。为了填补这一关键空白,我们开发了OcuPair,这是一种双组分水凝胶系统,它由:i)一种可注射的粘弹性填充物组成,该填充物可稳定眼腔并防止低眼压;ii)一种原位光固化粘合剂水凝胶,由甲基丙烯酸化的羟基PAMAM树枝状大分子和透明质酸组成,设计成在90秒内形成透明、灵活且坚固的绷带,粘附在角膜表面并确保水密密封,固定全层角膜伤口。体外研究表明,这种粘合剂水凝胶机械性能强大,能够承受超出生理范围的眼内压。在兔角膜损伤模型中,OcuPair有效地封闭了复杂的全层伤口,并在5天内保持眼睛良好的临床结果,30天内无毒性。在本研究中,我们验证了中试规模合成、配方优化、GMP放大以及支持IDE的GLP毒性,这些对于作为战场可用解决方案进行临床转化至关重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f023/12199432/08a6d674025d/ADVS-12-2417731-g002.jpg

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