Kambhampati Siva P, Sharma Rishi, Lin Hui, Appiani Santiago, Cleland Jeffrey L, Yiu Samuel C, Kannan Rangaramanujam M
Center for Nanomedicine, Wilmer Eye Institute, Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Ashvattha Therapeutics, Inc., Baltimore, MD, USA.
Adv Sci (Weinh). 2025 Jun;12(23):e2417731. doi: 10.1002/advs.202417731. Epub 2025 Mar 27.
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.
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。
