Buznyk Oleksiy, Azharuddin Mohammad, Islam Mohammad M, Fagerholm Per, Pasyechnikova Nataliya, Patra Hirak K
Department of Clinical and Experimental Medicine, Linköping University, Linköping 581 83, Sweden.
Filatov Institute of Eye Diseases and Tissue Therapy of the NAMS of Ukraine, 49/51 Frantsuzkyi Bulvar, Odessa 65061, Ukraine.
Heliyon. 2020 Oct 2;6(10):e05105. doi: 10.1016/j.heliyon.2020.e05105. eCollection 2020 Oct.
Currently the only widely accepted corneal blindness treatment is human donor cornea transplantation. However, increasing shortage of donor corneas as well as high risk of rejection in some corneal diseases remain two major problems, which limit the success of corneal transplantation. Corneal neovascularization is considered as one of the main risk factors of graft failure. Different cell-free biosynthetic scaffolds fabricated from collagens or collagen-like peptides are being tested as donor cornea substitutes (DCS). Here, we report for the first-time composite biosynthetic DCS with integrated sustained release system of anti-VEGF drug, bevacizumab and their preliminary in vitro validation. We have tethered gold nanoparticles with bevacizumab and integrated into a collagen-based cell-free hydrogel scaffold. Developed grafts preserved good optical properties and were confirmed not toxic to human corneal epithelial cells. Bevacizumab has been shown to constantly releasing from the DCS up to 3 weeks and preserved its anti-angiogenic properties. These results provide background for further use of infused composite biosynthetic DCS with integrated nanosystem of bevacizumab sustained release in corneal disease accompanied by neovascularisation where conventional corneal transplantation might fail.
目前,唯一被广泛接受的角膜盲治疗方法是人类供体角膜移植。然而,供体角膜日益短缺以及某些角膜疾病中高排斥风险仍然是两个主要问题,这限制了角膜移植的成功率。角膜新生血管形成被认为是移植物失败的主要危险因素之一。由胶原蛋白或类胶原蛋白肽制成的不同无细胞生物合成支架正在作为供体角膜替代品(DCS)进行测试。在此,我们首次报告了具有抗VEGF药物贝伐单抗集成缓释系统的复合生物合成DCS及其初步体外验证。我们将贝伐单抗与金纳米颗粒连接并整合到基于胶原蛋白的无细胞水凝胶支架中。开发的移植物保留了良好的光学特性,并被证实对人角膜上皮细胞无毒。已证明贝伐单抗可从DCS持续释放长达3周,并保留其抗血管生成特性。这些结果为进一步使用具有贝伐单抗缓释纳米系统集成的注入式复合生物合成DCS治疗伴有新生血管形成的角膜疾病提供了背景,在这些疾病中传统角膜移植可能会失败。