Novel biomaterials and photocages with anti-viral activity for transplantation

理论基础和背景：单纯疱疹病毒(HSV)感染在角膜中的发病率每年仅在美国就高达50万例。一旦被感染，病毒就会潜伏，留在角膜和神经里。当重新激活时(通过一系列触发因素，包括特定的食物、阳光、手术)，患者将出现疾病复发。这种疾病会导致角膜表面溃疡到深度溃疡，神经敏感度的丧失导致瘢痕形成和角膜失明，甚至角膜穿孔。患者需要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潜伏期和再激活所致。因此，需要一种有效的治疗方法。目的：因此，我们的目标是利用组织工程和光化学的方法来开发一种有效的治疗方法。前言：研究：我们将结合我们之前在开发人工角膜方面的成功，将其植入猪体内，使角膜细胞和神经再生，并以新的方式提供抗病毒药物，如阿昔洛韦。我们将开发新型光笼，用于精确、可控地释放阿昔洛韦，并将其合并到角膜植入物中，以在手术期间释放药物，以防止HSV重新激活。我们还将测试抗病毒多肽，如LL-37，在对抗原发HSV感染和/或防止病毒重新激活方面的有效性。这将允许进行高风险的角膜移植，并将其移植到视网膜和眼睛其他内部，在这些部位，药物或生长因子需要随着时间的推移进行输送和激活，而不需要使用注射等侵入性技术。

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.