Novel biomaterials and photocages with anti-viral activity for transplantation

基本原理和背景：仅在美国，角膜的单纯疱疹病毒（HSV）感染每年的发病率就高达50万例。一旦感染，病毒就会潜伏在角膜和神经中。当重新激活时（通过一系列触发因素，包括某些食物，阳光，手术），患者会复发。该疾病导致角膜表面溃疡形成更深的溃疡，神经敏感性丧失导致瘢痕形成和角膜失明甚至角膜穿孔。患者接受全身抗病毒药物治疗，但角膜移植是恢复视力的首选治疗方法，尽管预后极差- 5年成功率为22%。预后不良是由于HSV的潜伏期和再激活。因此需要有效的治疗。目的：因此，我们的目标是利用组织工程和光化学方法开发有效的治疗方法。拟议的研究：我们将结合我们之前成功开发的人造角膜，将角膜细胞和神经再生植入猪体内，并以新的方式输送抗病毒药物，如阿昔洛韦。新型光笼将用于精确、可控地释放阿昔洛韦，并结合到角膜植入物中，在手术期间释放药物，以防止HSV再激活。我们还将测试抗病毒肽（如LL-37）在对抗原发性HSV感染和/或防止病毒再激活方面的功效。预期意义：我们的研究结果可能成为一种将药物输送到眼睛（不仅仅是角膜）并以生物光子学的方式释放的手段。这将允许高风险的角膜移植，以及视网膜和眼睛其他内部部位的移植，在这些部位，药物或生长因子需要随着时间的推移被输送和激活，而无需使用像注射这样的侵入性技术。

RATIONALE AND BACKGROUND: Herpes simplex virus (HSV) infections in the cornea has an incidenceof up to 500,000 cases each year in the US alone. Once infected, the virus becomes latent and remains withinthe cornea and nerves. When reactivated (by a range of triggers including certains foods, sunlight, surgery), thepatient will have recurrences of the disease. The disease leads to ulceration of the corneal surface to deeperullcerations, loss of nerve sensitivity leading to scarring and corneal blindness or even corneal perforation.Patients are treated with systemic anti-viral drugs but corneal transplantation is the treatment of choice torestore vision, even though the prognosis is extremely poor - 22% success over 5 years. The poor prognosis isdue to the HSV latency and reactivation. An effective treatment is therefore needed.OBJECTIVE: Our objective therefore is to develop an effective treatment, using tissue engineering andphotochemistry approaches.PROPOSED RESEARCH:We will combine our previous success in developing artificial corneas that have allowed corneal cell and nerveregeneration when implanted into pigs with new ways to delivery anti-viral drugs such as acyclovir. Novelphotocages will be developed for precise, controlled release of acyclovir, and incorporated into cornealimplants to release the drug during surgery to prevent HSV reactivation.We will also be testing the efficacy ofanti-viral peptides, e.g. LL-37, in combating primary HSV infection and/or preventing viral reactivation.EXPECTED SIGNIFICANCEOur results could become a means by which drugs can be delivered to the eye (not just the cornea) and releasedbio-photonically. This would allow for high risk corneal transplants and transplants to the retina and otherinternal parts of the eye where drugs or growth factors need to be delivered and activated over time, without theuse of invasive techniques like injection.