Synthetic Hydrogels Incorporating Hydrolytic/Nonhydrolytic Macromer Ratios Exhibit Improved Tunability of In Vivo Degradation and Immune Responses.

IF 9.6 2区 医学 Q1 ENGINEERING, BIOMEDICAL
Michael D Hunckler, Sophia Kioulaphides, Karen E Martin, Angelica L Torres, Graham F Barber, Stephen W Linderman, Rebecca S Schneider, Andrés J García
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引用次数: 0

Abstract

Proteolytically degradable hydrogels are widely used as delivery carriers in regenerative medicine. However, the in vivo degradation rate of these materials is difficult to control because of site-specific enzymatic activity, implant design, and disease state, impairing tissue regeneration. Hydrogels with crosslinks that degrade hydrolytically offer an alternate route to tune in vivo degradation profile. In this study, a synthetic 4-arm maleimide-terminated poly(ethylene glycol) (PEG-4MAL) hydrogel system that combines hydrolytic ester-linked PEG-4MAL (PEG-4eMAL) macromer with nondegradable amide-linked PEG-4MAL (PEG-4aMAL) macromer in various stoichiometric ratios to tune the degradability rate is engineered. The macromers are crosslinked with dithiothreitol (DTT) via thiol-maleimide click reaction. Rheological analysis shows that a family of PEG-4eMAL/PEG-4aMAL hydrogels has equivalent mechanical properties, but increasing the PEG-4eMAL content increases the rate of degradation in vitro and in vivo. PEG-4eMAL/PEG-4aMAL hydrogels support high viability of encapsulated human cells. Notably, the ratio of PEG-4eMAL/PEG-4aMAL modulates local immune cell recruitment when implanted in the subcutaneous space. These results establish the use of PEG-4eMAL/PEG-4aMAL hydrogels as a hydrolytically degradable platform to tune in vivo degradation and immune responses.

含有水解/非水解大分子比例的合成水凝胶具有更好的体内降解和免疫反应的可调性。
蛋白质降解水凝胶在再生医学中作为递送载体得到了广泛的应用。然而,由于位点特异性酶活性、植入物设计和疾病状态,这些材料的体内降解率难以控制,从而损害组织再生。具有水解降解交联的水凝胶为调节体内降解概况提供了另一种途径。在本研究中,设计了一种合成的4臂马来酰亚胺端聚乙二醇(PEG-4MAL)水凝胶体系,该体系将水解酯连接的PEG-4MAL (PEG-4eMAL)大分子与不可降解的酰胺连接的PEG-4MAL (PEG-4aMAL)大分子以不同的化学计量比来调节降解率。大分子通过巯基-马来酰亚胺键合反应与二硫苏糖醇(DTT)交联。流变学分析表明,一类PEG-4eMAL/PEG-4aMAL水凝胶具有相当的力学性能,但随着PEG-4eMAL含量的增加,其在体内和体外的降解速率都会增加。PEG-4eMAL/PEG-4aMAL水凝胶支持封装的人类细胞的高活力。值得注意的是,当植入皮下间隙时,PEG-4eMAL/PEG-4aMAL的比例调节了局部免疫细胞的募集。这些结果建立了PEG-4eMAL/PEG-4aMAL水凝胶作为调节体内降解和免疫反应的水解降解平台的使用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Advanced Healthcare Materials
Advanced Healthcare Materials 工程技术-生物材料
CiteScore
14.40
自引率
3.00%
发文量
600
审稿时长
1.8 months
期刊介绍: Advanced Healthcare Materials, a distinguished member of the esteemed Advanced portfolio, has been dedicated to disseminating cutting-edge research on materials, devices, and technologies for enhancing human well-being for over ten years. As a comprehensive journal, it encompasses a wide range of disciplines such as biomaterials, biointerfaces, nanomedicine and nanotechnology, tissue engineering, and regenerative medicine.
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