Abstract

The development of hybrid hydrogels has been of great interest over recent decades, especially in the field of biomaterials. Such hydrogels provide various opportunities in tissue engineering, drug delivery, and regenerative medicine due to their ability to mimic cellular environments, sequester and release therapeutic agents, and respond to stimuli. Herein we report the synthesis and characterization of an injectable poly(ethylene glycol) hydrogel crosslinked via thiol-maleimide reactions and containing both chemically crosslinked temperature-sensitive liposomes (TSLs) and matrix metalloproteinase-sensitive peptide crosslinks. Rheological studies demonstrate that the hydrogel is mechanically stable and can be synthesized to achieve a range of physically applicable moduli. Experiments characterizing the in situ drug delivery and degradation of these materials indicate that the TSL gel responds to both thermal and enzymatic stimuli in a local environment. Doxorubicin, a widely used anticancer drug, was loaded in the TSLs with a high encapsulation efficiency and the subsequent release was temperature dependent. Finally, TSLs did not compromise viability and proliferation of human and murine fibroblasts, supporting the use of these hydrogel-linked liposomes as a thermo-responsive drug carrier for controlled release.

摘要

近几十年来，杂化水凝胶的发展引起了人们的极大兴趣，特别是在生物材料领域。这种水凝胶由于其模拟细胞环境、隔离和释放治疗剂以及对刺激做出反应的能力，为组织工程、药物输送和再生医学提供了各种机会。在此，我们报告了通过硫醇-马来酰亚胺反应交联的可注射聚乙二醇水凝胶的合成和表征，该水凝胶含有化学交联的温度敏感脂质体（TSL）和基质金属蛋白酶敏感肽交联。流变学研究表明，水凝胶具有机械稳定性，并且可以合成以获得一系列物理适用的模量。表征这些材料的原位药物输送和降解的实验表明，TSL 凝胶对局部环境中的热刺激和酶刺激都有反应。阿霉素是一种广泛使用的抗癌药物，以高封装效率装载在 TSL 中，并且随后的释放具有温度依赖性。最后，TSL 不会损害人和鼠成纤维细胞的活力和增殖，支持使用这些水凝胶连接的脂质体作为热响应药物载体进行控释。