Di Martino Miriam, Sessa Lucia, Romano Federica, Piotto Stefano, Concilio Simona
Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132, 84084 Fisciano, SA, Italy.
Bionam Center for Biomaterials, University of Salerno, Via Giovanni Paolo II, 132, 84084 Fisciano, SA, Italy.
Polymers (Basel). 2025 Aug 29;17(17):2350. doi: 10.3390/polym17172350.
Thermoresponsive hydrogels that undergo reversible sol-gel transitions near physiological temperatures are highly attractive for biomedical applications, such as injectable drug delivery and embolization therapies. In this study, a library of polyurethane-based hydrogels was synthesized via step-growth polymerization using polyethylene glycol (PEG) of varying molecular weights, different diisocyanates, and a series of functional diols derived from diethanolamine with increasing hydrophobicity. The resulting polymers exhibited sol-gel transition behaviors without the need for external crosslinkers, relying solely on non-covalent interactions. The thermal responsiveness was systematically investigated using UV-Vis turbidimetry, and the cloud point temperature (T) was found to be tunable within a range of 26-49 °C by modulating the monomer composition. Statistical modeling identified PEG molecular weight and diol structure as the primary determinants of T, while diisocyanate type and diol-to-PEG ratio had negligible effects. Only diethanolamine (DEA)-based polymers formed stable hydrogels above a critical gelation temperature (LCGT), attributed to enhanced intermolecular interactions via free amine groups. In vitro degradation assays confirmed good hydrolytic stability under physiological conditions over four weeks, with degradation profiles strongly influenced by the PEG chain length and hydrophobic content. These findings establish a structure-property framework for the rational design of injectable, thermoresponsive polyurethane hydrogels with tailored sol-gel behavior for biomedical applications.
在生理温度附近经历可逆溶胶-凝胶转变的热响应性水凝胶对于生物医学应用极具吸引力，例如可注射药物递送和栓塞疗法。在本研究中，通过逐步增长聚合反应，使用不同分子量的聚乙二醇（PEG）、不同的二异氰酸酯以及一系列由二乙醇胺衍生的疏水性逐渐增加的功能性二醇，合成了一系列基于聚氨酯的水凝胶。所得聚合物表现出溶胶-凝胶转变行为，无需外部交联剂，仅依靠非共价相互作用。使用紫外-可见比浊法系统地研究了热响应性，通过调节单体组成，发现浊点温度（T）可在26-49°C范围内调节。统计建模确定PEG分子量和二醇结构是T的主要决定因素，而二异氰酸酯类型和二醇与PEG的比例影响可忽略不计。只有基于二乙醇胺（DEA）的聚合物在临界凝胶化温度（LCGT）以上形成稳定的水凝胶，这归因于通过游离胺基团增强的分子间相互作用。体外降解试验证实，在生理条件下四周内具有良好的水解稳定性，降解情况受PEG链长和疏水含量的强烈影响。这些发现为合理设计具有定制溶胶-凝胶行为的可注射热响应性聚氨酯水凝胶以用于生物医学应用建立了结构-性能框架。
