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首页> 外文学位 >Microencapsulation of a Connexin-43 Mimetic Peptide as a Novel Wound Healing Agent in an Ocular Injury Model.
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Microencapsulation of a Connexin-43 Mimetic Peptide as a Novel Wound Healing Agent in an Ocular Injury Model.

机译：连接蛋白-43模拟肽作为新型创伤愈合剂在眼外伤模型中的微囊化。

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摘要

Corneal transplantation and related surgical procedures are areas of tissue replacement which have seen promising advances. Currently, cornea transplants are one of the most common surgical procedures, with approximately 40,000 occurring each year in the United States. Still, problems exist with a 20% rejection rate, post surgical infections, and the need for a constant supply of donors. The ability to safely and quickly heal and regenerate corneal epithelia fills an area of advancement in regenerative medicine, with implications reaching beyond the scope of vision therapies toward healing of a wide range of tissues and wounds. In vivo corneal wounds were created in rats through a surgical procedure chemically loosening and mechanically removing the epithelium from the corneal surface. Our study applies a synthetically developed peptide capable of promotion of wound healing and epithelial regeneration. The alpha-carboxy terminus 1 (αCT1) peptide is a 25 amino acid peptide from the C-terminus of connexin 43, modified to promote cellular uptake. Previous studies applying αCT1 to excisional wounds in rats produced resulting tissue having an overall reduced level of scar tissue and decreased healing time, compared to controls. Upon entering the wound site, the peptide acts as a competitive inhibitor to the ZO-1-Cx43 interaction. In doing so, the formation of gap junctions during healing is altered. Here we first characterized the development and synthesis of alginate based microcapsules, designed to deliver αCT1 in a controlled and sustained release. We hypothesized sustained release of αCT1 would enhance the peptides innate wound healing ability beyond previous results. An alginate-poly-l-ornithine pH 4.3 microcapsule capable of delivery of 150µM of peptide over 48hrs was ultimately produced. Both directly applied αCT1 in a pluronic gel system and microencapsulated αCT1 were tested in two studies of in vivo corneal wound injuries using normal and STZ type I diabetic Sprague Dawley rats. Data derived from RT-PCR, confocal immunohistochemistry, inflammatory H&E scoring, western blotting, Elisa protein analysis, and fluorescent wound measurements indicated a significant increase in wound healing speed when αCT1 was applied at a 150µM concentration. The application of 150µM αCT1 alginate-poly-l-ornithine pH 4.3 microcapsules further increased corneal wound healing rate beyond those seen when using αCT1 alone.
机译：角膜移植和相关的外科手术是组织替代领域，已经取得了可喜的进展。当前，角膜移植是最常见的外科手术之一，在美国每年约有40,000例发生。仍然存在20％拒绝率，手术后感染以及需要持续供应供体的问题。安全，快速治愈和再生角膜上皮的能力填补了再生医学的一个发展领域，其影响已超出视力疗法的范围，无法治愈广泛的组织和伤口。通过外科手术在大鼠中产生体内角膜伤口，该手术过程从角膜表面化学松弛并机械去除上皮。我们的研究应用了能够促进伤口愈合和上皮再生的合成开发肽。 α-羧基末端1（αCT1）肽是来自连接蛋白43 C末端的25个氨基酸的肽，经过修饰可促进细胞摄取。与对照组相比，先前将αCT1应用于大鼠切除伤口的研究产生的组织，其瘢痕组织水平总体降低，愈合时间缩短。进入伤口部位后，该肽可作为ZO-1-Cx43相互作用的竞争性抑制剂。这样做可以改变愈合过程中间隙连接的形成。在这里，我们首先表征了藻酸盐基微胶囊的开发和合成，该微胶囊旨在以受控和持续释放的方式递送αCT1。我们假设αCT1的持续释放将增强肽固有的伤口愈合能力，超出以往的结果。最终生产出能够在48小时内递送150µM肽的藻酸盐-聚-1-鸟氨酸pH 4.3微胶囊。在正常和STZ型I型糖尿病Sprague Dawley大鼠体内角膜伤口损伤的两项研究中，对直接应用于普鲁尼克凝胶系统中的αCT1和微囊化的αCT1进行了测试。来自RT-PCR，共聚焦免疫组织化学，H＆E炎性评分，蛋白质印迹，Elisa蛋白分析和荧光伤口测量的数据表明，当以150µM的浓度施用αCT1时，伤口愈合速度显着提高。 150μMpH的αCT1海藻酸盐-聚-1-鸟氨酸pH 4.3微胶囊的应用进一步提高了角膜伤口的愈合速度，超过了单独使用αCT1时的愈合速度。

著录项

  • 作者

    Moore, Keith Brian.;

  • 作者单位

    University of South Carolina.;

  • 授予单位 University of South Carolina.;
  • 学科 Health Sciences Ophthalmology.;Engineering Biomedical.
  • 学位 Ph.D.
  • 年度 2013
  • 页码 137 p.
  • 总页数 137
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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