Marco-Dufort Bruno, Janczy John R, Hu Tianjing, Lütolf Marco, Gatti Francesco, Wolf Morris, Woods Alex, Tetter Stephan, Sridhar Balaji V, Tibbitt Mark W
Macromolecular Engineering Laboratory, Department of Mechanical and Process Engineering, ETH Zurich, 8092 Zurich, Switzerland.
Nanoly Bioscience Inc., Denver, CO 80231, USA.
Sci Adv. 2022 Aug 5;8(31):eabo0502. doi: 10.1126/sciadv.abo0502.
Improving the thermal stability of biologics, including vaccines, is critical to reduce the economic costs and health risks associated with the cold chain. Here, we designed a versatile, safe, and easy-to-use reversible PEG-based hydrogel platform formed via dynamic covalent boronic ester cross-linking for the encapsulation, stabilization, and on-demand release of biologics. Using these reversible hydrogels, we thermally stabilized a wide range of biologics up to 65°C, including model enzymes, heat-sensitive clinical diagnostic enzymes (DNA gyrase and topoisomerase I), protein-based vaccines (H5N1 hemagglutinin), and whole viruses (adenovirus type 5). Our data support a generalized protection mechanism for the thermal stabilization of diverse biologics using direct encapsulation in reversible hydrogels. Furthermore, preliminary toxicology data suggest that the components of our hydrogel are safe for in vivo use. Our reversible hydrogel platform offers a simple material solution to mitigate the costs and risks associated with reliance on a continuous cold chain for biologic transport and storage.
提高生物制品（包括疫苗）的热稳定性对于降低与冷链相关的经济成本和健康风险至关重要。在此，我们设计了一种通用、安全且易于使用的基于聚乙二醇的可逆水凝胶平台，该平台通过动态共价硼酸酯交联形成，用于生物制品的封装、稳定化和按需释放。使用这些可逆水凝胶，我们在高达65°C的温度下对多种生物制品进行了热稳定处理，包括模型酶、热敏临床诊断酶（DNA促旋酶和拓扑异构酶I）、基于蛋白质的疫苗（H5N1血凝素）和全病毒（5型腺病毒）。我们的数据支持了一种通用的保护机制，即通过将不同的生物制品直接封装在可逆水凝胶中来实现热稳定。此外，初步毒理学数据表明，我们水凝胶的成分在体内使用是安全的。我们的可逆水凝胶平台提供了一种简单的材料解决方案，以减轻因依赖生物制品运输和储存的连续冷链而产生的成本和风险。
