Mitigation of diabetes-related complications in implanted collagen and elastin scaffolds using matrix-binding polyphenol
Mitigation of diabetes-related complications in implanted collagen and elastin scaffolds using matrix-binding polyphenol
复制标题
DOI：
10.1016/j.biomaterials.2012.09.081
复制
发表时间：
2013-01-01
期刊：
影响因子：
14
通讯作者：
Simionescu, Agneta
中科院分区：
文献类型：
--
作者：
Chow, James P.;Simionescu, Dan T.;Simionescu, Agneta
糖尿病心血管患者非常需要具有长期通畅性和耐用性的基于支架的组织工程血管移植物和心脏瓣膜。我们假设糖尿病通过糖氧化反应可以直接交联植入的支架，从而极大地改变其特性。为了研究组织工程支架在糖尿病条件下的命运，我们通过脱细胞制备了瓣膜胶原支架和动脉弹性蛋白支架，并将其植入糖尿病大鼠皮下。两种类型的支架都表现出显着水平的晚期糖基化终产物（AGES）、化学交联和硬化改变，这不利于心血管组织工程。使用五没食子酰葡萄糖（PGG）（一种抗氧化剂和基质结合多酚）对胶原蛋白和弹性蛋白支架进行植入前处理，可以化学稳定支架，减少其酶促降解，并通过降低支架结合的 AGE 水平来保护它们免受糖尿病相关并发症的影响。经过 PGG 处理的支架可以抵抗糖尿病引起的交联和硬化，防止钙化，并在体内表现出受控的重塑，从而支持未来将抗糖尿病支架用于糖尿病患者的心血管组织工程。由爱思唯尔有限公司出版
There is a major need for scaffold-based tissue engineered vascular grafts and heart valves with long-term patency and durability to be used in diabetic cardiovascular patients. We hypothesized that diabetes, by virtue of glycoxidation reactions, can directly crosslink implanted scaffolds, drastically altering their properties. In order to investigate the fate of tissue engineered scaffolds in diabetic conditions, we prepared valvular collagen scaffolds and arterial elastin scaffolds by decellularization and implanted them subdermally in diabetic rats. Both types of scaffolds exhibited significant levels of advanced glycation end products (AGES), chemical crosslinking and stiffening -alterations which are not favorable for cardiovascular tissue engineering. Pre-implantation treatment of collagen and elastin scaffolds with penta-galloyl glucose (PGG), an antioxidant and matrix-binding polyphenol, chemically stabilized the scaffolds, reduced their enzymatic degradation, and protected them from diabetes-related complications by reduction of scaffold-bound AGE levels. PGG-treated scaffolds resisted diabetes-induced crosslinking and stiffening, were protected from calcification, and exhibited controlled remodeling in vivo, thereby supporting future use of diabetes-resistant scaffolds for cardiovascular tissue engineering in patients with diabetes. Published by Elsevier Ltd.