Xu Cancan, Huang Yihui, Wu Jinglei, Tang Liping, Hong Yi
Department of Bioengineering, University of Texas at Arlington , Arlington, Texas 76019, United States.
Joint Biomedical Engineering Program, University of Texas Southwestern Medical Center , Dallas, Texas 75390, United States.
ACS Appl Mater Interfaces. 2015 Sep 16;7(36):20377-88. doi: 10.1021/acsami.5b06242. Epub 2015 Sep 3.
Tissue engineered and bioactive scaffolds with different degradation rates are required for the regeneration of diverse tissues/organs. To optimize tissue regeneration in different tissues, it is desirable that the degradation rate of scaffolds can be manipulated to comply with various stages of tissue regeneration. Unfortunately, the degradation of most degradable polymers relies solely on passive controlled degradation mechanisms. To overcome this challenge, we report a new family of reduction-sensitive biodegradable elastomeric polyurethanes containing various amounts of disulfide bonds (PU-SS), in which degradation can be initiated and accelerated with the supplement of a biological product: antioxidant-glutathione (GSH). The polyurethanes can be processed into films and electrospun fibrous scaffolds. Synthesized materials exhibited robust mechanical properties and high elasticity. Accelerated degradation of the materials was observed in the presence of GSH, and the rate of such degradation depends on the amount of disulfide present in the polymer backbone. The polymers and their degradation products exhibited no apparent cell toxicity while the electrospun scaffolds supported fibroblast growth in vitro. The in vivo subcutaneous implantation model showed that the polymers prompt minimal inflammatory responses, and as anticipated, the polymer with the higher disulfide bond amount had faster degradation in vivo. This new family of polyurethanes offers tremendous potential for directed scaffold degradation to promote maximal tissue regeneration.
不同组织/器官的再生需要具有不同降解速率的组织工程和生物活性支架。为了优化不同组织中的组织再生,理想的情况是能够控制支架的降解速率,使其与组织再生的各个阶段相匹配。不幸的是,大多数可降解聚合物的降解仅依赖于被动控制的降解机制。为了克服这一挑战,我们报道了一类新的对还原敏感的可生物降解弹性体聚氨酯(PU-SS),其含有不同量的二硫键,在添加生物产物抗氧化剂谷胱甘肽(GSH)时可引发并加速降解。这些聚氨酯可加工成薄膜和电纺纤维支架。合成材料表现出强大的机械性能和高弹性。在GSH存在下观察到材料加速降解,且降解速率取决于聚合物主链中存在的二硫键数量。聚合物及其降解产物没有明显的细胞毒性,而电纺支架在体外支持成纤维细胞生长。体内皮下植入模型表明,这些聚合物引发的炎症反应最小,并且正如预期的那样,二硫键含量较高的聚合物在体内降解更快。这一新的聚氨酯家族为定向支架降解以促进最大程度的组织再生提供了巨大潜力。