Injectable thermoresponsive hydrogels (thermogels), valued for their conformability and minimal invasiveness, are increasingly used as in situ forming implants for drug delivery and as regenerative scaffolds. These gels exhibit sol-to-gel phase transitions at body temperature. As localized depots and scaffolds, these gels determine the chemical and mechanical environments and could dramatically influence the release kinetics of drugs or the fate of cells. Current synthetic approaches for thermogels, however, often limit the ability to fully exploit interactions between the thermogel matrix and the encapsulated agent. In this study, we introduce a modular synthetic platform for creating a library of functionalized polyurethane thermogels that enables customization of gelation properties and intermolecular interactions. These thermogels can exhibit a wide range of stiffness, offer complementary ionic interactions, and enhance hydrophobic interactions and hydrogen bonding. By leveraging these tunable interactions between the thermogelling scaffold, functional groups, and encapsulated agents, we achieved sustained and controlled release, from days to over 6 months, for both low and high molecular weight drug analogs. Release profiles varied from monophasic to biphasic and triphasic depending on the compatibility between the thermogel properties and the encapsulated agents. The design rules identified here support the development of drug-specific formulations, facilitating precise, sustained, and modulated release tailored to therapeutic needs. Beyond providing an adaptable strategy for customizable injectable drug depots, this synthetic strategy lays the groundwork for future iterations of multi stimuli-responsive thermogels with enhanced bioactivity, advancing the potential for customizable, biointeractive therapeutic systems.

中文翻译：

---

模块化合成平台，可在注射水凝胶中定制治疗特异性递送


可注射的热响应性水凝胶（热凝胶）因其顺应性和最小侵入性而受到重视，越来越多地用作药物输送的原位形成植入物和再生支架。这些凝胶在体温下表现出溶胶到凝胶的相变。作为定位的贮库和支架，这些凝胶决定了化学和机械环境，并可能极大地影响药物的释放动力学或细胞的命运。然而，目前的热凝胶合成方法通常限制了充分利用热凝胶基质和封装剂之间相互作用的能力。在这项研究中，我们介绍了一个模块化合成平台，用于创建功能化聚氨酯热凝胶库，该平台可以定制凝胶特性和分子间相互作用。这些热凝胶可以表现出广泛的刚度，提供互补的离子相互作用，并增强疏水相互作用和氢键。通过利用热凝胶支架、官能团和包封剂之间的这些可调相互作用，我们实现了低分子量和高分子量药物类似物的持续和受控释放，从几天到六个月以上。释放曲线从单相到双相和三相不等，具体取决于热凝胶特性和包封剂之间的相容性。此处确定的设计规则支持药物特异性制剂的开发，促进根据治疗需求量身定制的精确、持续和调节释放。 除了为可定制的注射药物库提供适应性策略外，这种合成策略还为具有增强生物活性的多刺激响应热凝胶的未来迭代奠定了基础，从而推动了可定制的生物交互式治疗系统的潜力。