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含有抗病毒GF19肽的抑制炎症的注射器式角膜促进单纯疱疹病毒1型感染的兔角膜再生。

Inflammation-suppressing cornea-in-a-syringe with anti-viral GF19 peptide promotes regeneration in HSV-1 infected rabbit corneas.

作者信息

Simoliunas Egidijus, Ruedas-Torres Inés, Jiménez-Gómez Yolanda, Edin Elle, Aghajanzadeh-Kiyaseh Mozhgan, Zamani-Roudbaraki Mostafa, Asoklis Rimvydas, Alksne Milda, Thathapudi Neethi C, Poudel Bijay K, Rinkunaite Ieva, Asoklis Kasparas, Iesmantaite Monika, Ortega-Llamas Laura, Makselis Almantas, Munoz Marcelo, Baltriukiene Daiva, Bukelskiene Virginija, Gómez-Laguna Jaime, González-Andrades Miguel, Griffith May

机构信息

Department of Biological Models, Institute of Biochemistry, Life Sciences Center, Vilnius University, Vilnius, Lithuania.

Department of Anatomy and Comparative Pathology and Toxicology, Pathology and Immunology Group (UCO-PIG), UIC Zoonosis y Enfermedades Emergentes ENZOEM, University of Córdoba, International Excellence Agrifood Campus 'CeiA3', 14014, Córdoba, Spain.

出版信息

NPJ Regen Med. 2024 Mar 1;9(1):11. doi: 10.1038/s41536-024-00355-1.

Abstract

Pathophysiologic inflammation, e.g., from HSV-1 viral infection, can cause tissue destruction resulting in ulceration, perforation, and ultimately blindness. We developed an injectable Cornea-in-a-Syringe (CIS) sealant-filler to treat damaged corneas. CIS comprises linear carboxylated polymers of inflammation-suppressing 2-methacryloyloxyethyl phosphorylcholine, regeneration-promoting collagen-like peptide, and adhesive collagen-citrate glue. We also incorporated GF19, a modified anti-viral host defense peptide that blocked HSV-1 activity in vitro when released from silica nanoparticles (SiNP-GF19). CIS alone suppressed inflammation when tested in a surgically perforated and HSV-1-infected rabbit corneal model, allowing tissue and nerve regeneration. However, at six months post-operation, only regenerated neocorneas previously treated with CIS with SiNP-GF19 had structural and functional features approaching those of normal healthy corneas and were HSV-1 virus-free. We showed that composite injectable biomaterials can be designed to allow regeneration by modulating inflammation and blocking viral activity in an infected tissue. Future iterations could be optimized for clinical application.

摘要

病理生理性炎症,例如由单纯疱疹病毒1型(HSV-1)感染引起的炎症,可导致组织破坏,进而造成溃疡、穿孔,并最终导致失明。我们研发了一种可注射的“注射器中的角膜”(CIS)密封剂-填充剂来治疗受损角膜。CIS由具有抗炎作用的2-甲基丙烯酰氧基乙基磷酰胆碱的线性羧化聚合物、促进再生的类胶原蛋白肽以及粘性胶原柠檬酸盐胶水组成。我们还加入了GF19,这是一种经过修饰的抗病毒宿主防御肽,当它从二氧化硅纳米颗粒(SiNP-GF19)中释放出来时,能在体外阻断HSV-1的活性。在手术穿孔并感染HSV-1的兔角膜模型中进行测试时,单独使用CIS就能抑制炎症,促进组织和神经再生。然而,在术后六个月时,只有之前用含有SiNP-GF19的CIS治疗过的再生新角膜具有接近正常健康角膜的结构和功能特征,并且没有HSV-1病毒。我们表明,可以设计复合可注射生物材料,通过调节炎症和阻断感染组织中的病毒活性来实现组织再生。未来的迭代产品可针对临床应用进行优化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/85c7/10907611/72a848b9cb23/41536_2024_355_Fig1_HTML.jpg

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