(Iminium)thiolactone-Functional Hyaluronic Acid Hydrogels as Tissue Engineering Scaffolds

(亚胺)硫内酯-功能性透明质酸水凝胶作为组织工程支架

• 批准号: 392874313
• 负责人: Dr. Stefan Mommer
• 金额: --
• 依托单位: Yusuf Hamied Department of Chemistry
• 依托单位国家: 德国
• 项目类别: Research Fellowships
• 财政年份: 2017
• 资助国家: 德国
• 起止时间: 2016-12-31 至 2017-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/392874313?language=en
• 关键词: Iminium; thiolactone; Functional; Hyaluronic; Acid

A novel materials platform is established which is aimed for the treatment of chronic wounds. Chronic wounds play a major part for which millions of people suffer from and a substantial share of costs comes to burden of the national health insurance systems. They are mostly stuck in an inflammatory stage of the healing process. This inflammatory state hinders the supporting cells to sequester fresh and healthy components of the human extracellular matrix (ECM). The main component is hyaluronic acid, which has become a prominent ingredient for cosmetics or anti-aging products and is also found in the human ECM. Therefore, hyaluronic acid is modified with a chemical functionality (thiolactones). The synthesis of these thiolactones is accomplished, and strategies for the attachment to hyaluronic acid are elaborated. The tholactones bound the the hyaluronic acid backbone offer the possibity to bind peptides and proteins such as binding/growth factors directly to the hyaluronic acid for cell signaling and stimulation of growth. The thiolactones have often been used for the modification of large proteins or enzymes, because they show good reactivity towards the amino groups of respective proteins. In a second reaction step, either guest or host molecules for cucubituril chemistry are reacted with the thiols (released from the thiolactone after ring-opening at the first reaction step). Cucuriturils are macrocyclic molecules, which can host certain positively charged guest molecules to form stable inclusion complexes. The interaction of host and guest proceeds in a non-covalent manner. This reaction strategy will allow (i) the covalent incorporation of growth/binding factors, drug agents and peptides/proteins to the hyaluronic acid and (ii) the non-covalent cross-linking. The latter delivers a material which is extremely malleable and, through shape remodeling, maintains high surface area contact with a surface of interest. Thus, spacial adaption to the individual morphology of the wound is possible. Prior to this final application, the embedding and proliferation of healthy cells in this gel as 3D scaffold is investigated and tuned to favour the thriving and growth of the used cells. In our approach, this material can substitute the defective ECM and promote the embedded cells to remodel and regenerate naturally occuring ECM components. As the healing process is re-boosted, the artificial ECM will be slowly degraded and replaced by the body's own.

建立了一个新的材料平台，旨在治疗慢性伤口。慢性创伤是数百万人遭受痛苦的主要原因，国家健康保险系统负担了很大一部分费用。他们大多停留在愈合过程的炎症阶段。这种炎症状态阻碍了支持细胞隔离人类细胞外基质（ECM）的新鲜和健康成分。主要成分是透明质酸，它已成为化妆品或抗衰老产品的重要成分，也存在于人体ECM中。因此，透明质酸被化学官能团（硫代内酯）修饰。完成这些硫代内酯的合成，并阐述了与透明质酸连接的策略。与透明质酸主链结合的tholactones提供了将肽和蛋白质如结合/生长因子直接结合到透明质酸的可能性，用于细胞信号传导和刺激生长。 硫代内酯通常用于大蛋白质或酶的修饰，因为它们对相应蛋白质的氨基显示出良好的反应性。在第二反应步骤中，用于萌芦脲化学的客体或主体分子与硫醇（在第一反应步骤中开环后从硫代内酯释放）反应。瓜环是一种大环分子，它可以与某些带正电荷的客体分子形成稳定的包合物。主体和客体的相互作用以非共价方式进行。该反应策略将允许（i）将生长/结合因子、药物试剂和肽/蛋白质共价掺入透明质酸和（ii）非共价交联。后者提供了一种极具延展性的材料，并且通过形状重塑，保持与感兴趣表面的高表面积接触。因此，空间适应伤口的个体形态是可能的。在最终应用之前，研究并调整健康细胞在这种凝胶中作为3D支架的嵌入和增殖，以促进所用细胞的蓬勃发展和生长。在我们的方法中，这种材料可以替代有缺陷的ECM，并促进嵌入的细胞重塑和再生天然存在的ECM成分。随着愈合过程的重新推进，人造ECM将慢慢降解并被身体自身所取代。