Construction of Injectable Self-Healing Macroporous Hydrogels via a Template-Free Method for Tissue Engineering and Drug Delivery
Construction of Injectable Self-Healing Macroporous Hydrogels via a Template-Free Method for Tissue Engineering and Drug Delivery
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通过无模板方法构建可注射自愈大孔水凝胶，用于组织工程和药物输送
DOI：
10.1021/acsami.8b13077
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发表时间：
2018-10-31
影响因子：
9.5
通讯作者：
Li, Lingli
中科院分区：
文献类型：
--
作者：
Wang, Lei;Deng, Fen;Li, Lingli
可注射大孔水凝胶因其易于操作和良好的生物相容性，在组织工程和药物输送系统领域因其在微创外科手术中的独特应用而受到极大的关注。本研究采用高速剪切法制备了原位成型、可注射、大孔、自愈合的明胶(GE)/氧化海藻酸盐(OSA)/己二酸二肼(ADH)水凝胶，并通过席夫碱反应和酰肼键对凝胶进行了稳定。对其注射性、自愈性、流变性、微观结构、平衡含水率和体外生物降解性进行了研究。我们发现，可注射的Ge/OSA/ADH前体在室温下仍以液体形式存在，并易于流动数分钟，但在体温下可迅速凝胶化。凝胶时间可以通过改变GE、OSA和ADH的比例来调节。所得到的水凝胶具有相互连接的大孔结构和自愈合能力。水凝胶的孔隙率约为60-83%，孔径约为125-380微米。用场发射扫描电子显微镜、微型计算机断层扫描和激光共聚焦显微镜观察了水凝胶的孔结构。人表皮生长因子以Ge/OSA/ADH水凝胶为载体，经原位混合后，释放出具有良好生物活性的凝胶。此外，细胞计数试剂盒8和活/死实验证实，L929细胞在GE/OSA/ADH水凝胶上增殖。此外，将NIH3T3细胞包裹在GE/OSA/ADH水凝胶中，表明该水凝胶可以支持细胞的存活、增殖和迁移。体内研究表明，该水凝胶具有良好的注射性、原位凝胶性和组织生物相容性。因此，GE/OSA/ADH水凝胶是一种新型、安全的可注射大孔自愈水凝胶，可用于组织工程支架和药物输送载体。
Because of their ease of handling and excellent biocompatibility, injectable macroporous hydrogels have received a considerable interest in the fields of tissue engineering and drug delivery systems because of their unique application in minimally invasive surgical procedures. In this study, in situ forming, injectable, macroporous, self-healing gelatin (GE)/oxidized alginate (OSA)/adipic acid dihydrazide (ADH) hydrogels were prepared using a highspeed shearing treatment and were stabilized by Schiff base reaction and acylhydrazone bonds. Their injectability, self-healing ability, rheology, microstructure, equilibrium water content, and in vitro biodegradation were investigated. We found that the injectable GE/OSA/ADH precursors remained in a liquid form and flowed easily for several minutes at room temperature, but however, gelled rapidly at body temperature. The gelation time could be regulated by varying the ratio of GE, OSA, and ADH. The obtained hydrogels had an interconnected macroporous structure and self-healing ability. The porosity of hydrogels was in the range of approximately 60-83%, and pore size varied from approximately 125-380 mu m. The porous structure of hydrogel was visualized by field-emission scanning electron microscope, micro -computed tomography, and laser confocal microscope. Human epidermal growth factor was loaded by in situ mixing in GE/OSA/ADH hydrogels and was released with good bioactivity as evaluated by ELISA. Moreover, L929 cells proliferated on GE/OSA/ADH hydrogels, as verified by Cell Counting Kit-8 and LIVE/DEAD assays. Furthermore, encapsulation of NIH 3T3 cells within GE/OSA/ADH hydrogels demonstrated that the hydrogel can support cell survival, proliferation, and migration. In vivo studies showed that the hydrogels had a good injectability, in situ gelation, and tissue biocompatibility. Therefore, GE/OSA/ADH hydrogel represented a novel and safe injectable macroporous self-healing hydrogel for tissue engineering scaffold and drug delivery vehicle purposes.