Juriga Dávid, Sipos Evelin, Hegedűs Orsolya, Varga Gábor, Zrínyi Miklós, Nagy Krisztina S, Jedlovszky-Hajdú Angéla
Laboratory of Nanochemistry, Department of Biophysics and Radiation Biology, Semmelweis University, Nagyvarad square 4, Budapest, Hungary.
Department of Oral Biology, Semmelweis University, Nagyvarad square 4, Budapest, Hungary.
Beilstein J Nanotechnol. 2019 Dec 27;10:2579-2593. doi: 10.3762/bjnano.10.249. eCollection 2019.
Polymer hydrogels are ideal scaffolds for both tissue engineering and drug delivery. A great advantage of poly(amino acid)-based hydrogels is their high similarity to natural proteins. However, their expensive and complicated synthesis often limits their application. The use of poly(aspartic acid) (PASP) seems an appropriate solution for this problem due to the relatively cheap and simple synthesis of PASP. Using amino acids not only as building blocks in the polymer backbone but also as cross-linkers can improve the biocompatibility and the biodegradability of the hydrogel. In this paper, PASP cross-linked with cystamine (CYS) and lysine-methylester (LYS) was introduced as fully amino acid-based polymer hydrogel. Gels were synthesized employing six different ratios of CYS and LYS. The pH dependent swelling degree and the concentration of the elastically active chain were determined. After reduction of the disulfide bonds of CYS, the presence of thiol side groups was also detected. To determine the concentration of the reactive cross-linkers in the hydrogels, a new method based on the examination of the swelling behavior was established. Using metoprolol as a model drug, cell proliferation and drug release kinetics were studied at different LYS contents and in the presence of thiol groups. The optimal ratio of cross-linkers for the proliferation of periodontal ligament cells was found to be 60-80% LYS and 20-40% CYS. The reductive conditions resulted in an increased drug release due to the cleavage of disulfide bridges in the hydrogels. Consequently, these hydrogels provide new possibilities in the fields of both tissue engineering and controlled drug delivery.
聚合物水凝胶是组织工程和药物递送的理想支架。基于聚氨基酸的水凝胶的一个巨大优势是它们与天然蛋白质高度相似。然而，其昂贵且复杂的合成过程常常限制了它们的应用。由于聚天冬氨酸（PASP）的合成相对便宜且简单，使用聚天冬氨酸似乎是解决这个问题的合适方案。不仅将氨基酸用作聚合物主链中的结构单元，还用作交联剂，可以提高水凝胶的生物相容性和生物降解性。在本文中，引入了与胱胺（CYS）和赖氨酸甲酯（LYS）交联的PASP作为完全基于氨基酸的聚合物水凝胶。使用六种不同比例的CYS和LYS合成凝胶。测定了pH依赖性溶胀度和弹性活性链的浓度。在还原CYS的二硫键后，还检测到了硫醇侧基的存在。为了测定水凝胶中反应性交联剂的浓度，建立了一种基于溶胀行为研究的新方法。使用美托洛尔作为模型药物，研究了在不同LYS含量和存在硫醇基团的情况下细胞增殖和药物释放动力学。发现用于牙周膜细胞增殖的交联剂的最佳比例为60 - 80% LYS和20 - 40% CYS。还原条件导致由于水凝胶中二硫键的断裂而使药物释放增加。因此，这些水凝胶在组织工程和可控药物递送领域都提供了新的可能性。
