Department of Biomedical Engineering, Louisiana Tech University, Ruston, LA, 71272, USA.
Macromol Biosci. 2023 Jun;23(6):e2200505. doi: 10.1002/mabi.202200505. Epub 2023 Apr 22.
In recent years, there has been an increased interest in injectable, in situ crosslinking hydrogels due to their minimally invasive application and ability to conform to their environment. Current in situ crosslinking chitosan hydrogels are either mechanically robust with poor biocompatibility and limited biodegradation due to toxic crosslinking agents or the hydrogels are mechanically weak and undergo biodegradation too rapidly due to insufficient crosslinking. Herein, the authors developed and characterized a thermally-driven, injectable chitosan-genipin hydrogel capable of in situ crosslinking at 37 °C that is mechanically robust, biodegradable, and maintain high biocompatibility. The natural crosslinker genipin is utilized as a thermally-driven, non-toxic crosslinking agent. The chitosan-genipin hydrogel's crosslinking kinetics, injectability, viscoelasticity, swelling and pH response, and biocompatibility against human keratinocyte cells are characterized. The developed chitosan-genipin hydrogels are successfully crosslinked at 37 °C, demonstrating temperature sensitivity. The hydrogels maintained a high percentage of swelling over several weeks before degrading in biologically relevant environments, demonstrating mechanical stability while remaining biodegradable. Long-term cell viability studies demonstrated that chitosan-genipin hydrogels have excellent biocompatibility over 7 days, including during the hydrogel crosslinking phase. Overall, these findings support the development of an injectable, in situ crosslinking chitosan-genipin hydrogel for minimally invasive biomedical applications.
近年来，由于可注射原位交联水凝胶具有微创应用和适应环境的能力，因此人们对其产生了浓厚的兴趣。目前的可注射原位交联壳聚糖水凝胶要么具有很强的机械强度，但生物相容性差，由于交联剂有毒而降解有限，要么机械强度较弱，由于交联不足而迅速降解。在此，作者开发并表征了一种热驱动的、可注射的壳聚糖-京尼平水凝胶，该水凝胶能够在 37°C 下原位交联，具有机械强度高、可生物降解和保持高生物相容性的特点。天然交联剂京尼平被用作热驱动的、无毒的交联剂。研究了壳聚糖-京尼平水凝胶的交联动力学、可注射性、粘弹性、溶胀和 pH 响应以及对人角质形成细胞的生物相容性。所开发的壳聚糖-京尼平水凝胶在 37°C 下成功交联，表现出温度敏感性。水凝胶在数周内保持高溶胀率，然后在生物相关环境中降解，表现出机械稳定性的同时仍然可生物降解。长期细胞活力研究表明，壳聚糖-京尼平水凝胶具有优异的生物相容性，持续 7 天，包括水凝胶交联阶段。总的来说，这些发现支持了一种可注射的原位交联壳聚糖-京尼平水凝胶的开发，用于微创生物医学应用。
