Department of Chemistry, Stanford University, Stanford, CA, 94305, USA.
Department of Materials Science and Engineering, Stanford University, Stanford, CA, 94305, USA.
Adv Mater. 2018 May;30(22):e1705215. doi: 10.1002/adma.201705215. Epub 2018 Apr 23.
Injectable and biocompatible hydrogels have become increasingly important for cell transplantation to provide mechanical protection of cells during injection and a stable scaffold for cell adhesion post-injection. Injectable hydrogels need to be easily pushed through a syringe needle and quickly recover to a gel state, thus generally requiring noncovalent or dynamic cross-linking. However, a dilemma exists in the design of dynamic hydrogels: hydrogels with fast exchange of cross-links are easier to eject using less force, but lack long-term stability; in contrast, slow exchange of cross-links improves stability, but compromises injectability and thus the ability to protect cells under flow. A new concept to resolve this dilemma using a biocompatible catalyst to modulate the dynamic properties of hydrogels at different time points of application to have both high injectability and high stability is presented. Hyaluronic acid based hydrogels are formed through dynamic covalent hydrazone cross-linking in the presence of a biocompatible benzimidazole-based catalyst. The catalyst accelerates the formation and exchange of hydrazone bonds, enhancing injectability, but rapidly diffuses away from the hydrogel after injection to retard the exchange and improve the long-term stability for cell culture.
可注射和生物相容的水凝胶在细胞移植中变得越来越重要，为细胞注射提供机械保护，并为细胞注射后提供稳定的附着支架。可注射水凝胶需要易于通过注射器针头推动，并迅速恢复凝胶状态，因此通常需要非共价或动态交联。然而，在设计动态水凝胶时存在一个困境：具有快速交联交换的水凝胶更容易在较小的力作用下射出，但缺乏长期稳定性；相反，缓慢的交联交换提高了稳定性，但会影响可注射性，从而影响在流动下保护细胞的能力。提出了一种新的概念，使用生物相容的催化剂在应用的不同时间点调节水凝胶的动态特性，以实现高可注射性和高稳定性。在存在生物相容的苯并咪唑基催化剂的情况下，透明质酸基水凝胶通过动态共价腙交联形成。催化剂加速了腙键的形成和交换，提高了可注射性，但在注射后迅速从水凝胶中扩散出来，以减缓交换并提高细胞培养的长期稳定性。
