Nourbakhsh Melika, Zarrintaj Payam, Jafari Seyed Hassan, Hosseini Sayed Masoud, Aliakbari Shayan, Pourbadie Hamid Gholami, Naderi Nima, Zibaii Mohammad Ismail, Gholizadeh Saman Seyed, Ramsey Joshua D, Thomas Sabu, Farokhi Mehdi, Saeb Mohammad Reza
School of Chemical Engineering, College of Engineering, University of Tehran, Tehran, Iran.
School of Chemical Engineering, Oklahoma State University, Stillwater, OK 74078, United States.
Mater Sci Eng C Mater Biol Appl. 2020 Dec;117:111328. doi: 10.1016/j.msec.2020.111328. Epub 2020 Aug 4.
The hippocampus, a critical cerebral region involved in learning and memory formation, is especially vulnerable to ischemic defect. Here, we developed an injectable electroactive hydrogel based on pluronic-chitosan/aniline-pentamer with proper conductivity around 10 S/cm to achieve the functional repair of the hippocampus following the ischemic defect. FTIR, DSC, and TGA measurements were performed to assess the chemical structure and thermal stability of the synthesized hydrogel. Aniline pentamer decreased the swelling capacity, degradation, and drug release rate. Further, contact angle, melting point, and gelation time of hydrogels were enhanced by addition of aniline oligomer. Moreover, it endowed the on-demand electro-responsive drug release. Injectability of hydrogel was evaluated by rheometry, exhibiting proper gelling time at the body temperature. The ionic/electrical conductivity and desired in vitro biocompatibility with PC12 cells were also achieved. Injection of VEGF-loaded electroactive hydrogel in the hippocampal ischemic animal model resulted in decreased infarction volume, improved hippocampal dependent learning, and memory performance. Taken all together, the results confirmed that fabricated injectable hydrogel would be a suitable candidate for ischemic defect treatment and can lead to new horizons to treat neurological disorders.
海马体是参与学习和记忆形成的关键脑区，特别容易受到缺血性损伤。在此，我们开发了一种基于普朗尼克-壳聚糖/苯胺五聚体的可注射电活性水凝胶，其电导率约为10 S/cm，以实现缺血性损伤后海马体的功能修复。进行了傅里叶变换红外光谱（FTIR）、差示扫描量热法（DSC）和热重分析法（TGA）测量，以评估合成水凝胶的化学结构和热稳定性。苯胺五聚体降低了水凝胶的溶胀能力、降解率和药物释放速率。此外，通过添加苯胺低聚物，提高了水凝胶的接触角、熔点和凝胶化时间。而且，它赋予了按需电响应药物释放功能。通过流变学评估了水凝胶的可注射性，其在体温下表现出合适的凝胶化时间。还实现了离子/电导率以及与PC12细胞所需的体外生物相容性。在海马体缺血动物模型中注射负载血管内皮生长因子（VEGF）的电活性水凝胶，可减少梗死体积，改善海马体依赖性学习和记忆性能。综上所述，结果证实所制备的可注射水凝胶将是缺血性损伤治疗的合适候选物，并可为治疗神经系统疾病带来新的前景。
