Woodruff School of Mechanical Engineering and Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, 315 Ferst Dr. NW, Atlanta, GA, 30332, USA.
Coulter Department of Biomedical Engineering, Georgia Institute of Technology, 313 Ferst Dr. NW, Atlanta, GA, 30332, USA.
Adv Healthc Mater. 2019 Jul;8(14):e1900371. doi: 10.1002/adhm.201900371. Epub 2019 May 21.
Thiol-norbornene (thiol-ene) photoclickable poly(ethylene glycol) (PEG) hydrogels are a versatile biomaterial for cell encapsulation, drug delivery, and regenerative medicine. Numerous in vitro studies with these 4-arm ester-linked PEG-norbornene (PEG-4eNB) hydrogels demonstrate robust cytocompatibility and ability to retain long-term integrity with nondegradable crosslinkers. However, when transplanted in vivo into the subcutaneous or intraperitoneal space, these PEG-4eNB hydrogels with nondegradable crosslinkers rapidly degrade within 24 h. This characteristic limits the usefulness of PEG-4eNB hydrogels in biomedical applications. Replacing the ester linkage with an amide linkage (PEG-4aNB) mitigates this rapid in vivo degradation, and the PEG-4aNB hydrogels maintain long-term in vivo stability for months. Furthermore, when compared to PEG-4eNB, the PEG-4aNB hydrogels demonstrate equivalent mechanical properties, crosslinking kinetics, and high cytocompatibility with rat islets and human mesenchymal stem cells. Thus, the PEG-4aNB hydrogels may be a suitable replacement platform without necessitating critical design changes or sacrificing key properties relevant to the well-established PEG-4eNB hydrogels.
巯基-降冰片烯（硫醇-烯）光点击可聚合聚乙二醇（PEG）水凝胶是一种用于细胞包封、药物输送和再生医学的多功能生物材料。大量体外研究表明，这些 4 臂酯键连接的 PEG-降冰片烯（PEG-4eNB）水凝胶具有很强的细胞相容性，并能够在不可降解的交联剂存在下保持长期完整性。然而，当将这些具有不可降解交联剂的 PEG-4eNB 水凝胶移植到皮下或腹腔内时，它们会在 24 小时内迅速降解。这种特性限制了 PEG-4eNB 水凝胶在生物医学应用中的用途。用酰胺键（PEG-4aNB）取代酯键可以减轻这种快速的体内降解，PEG-4aNB 水凝胶可以在体内保持数月的长期稳定性。此外，与 PEG-4eNB 相比，PEG-4aNB 水凝胶表现出等效的机械性能、交联动力学和对大鼠胰岛和人间充质干细胞的高细胞相容性。因此，PEG-4aNB 水凝胶可能是一种合适的替代平台，无需进行关键设计更改或牺牲与成熟的 PEG-4eNB 水凝胶相关的关键特性。
