3B's Research Group, I3Bs - Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark - Parque de Ciência e Tecnologia, Zona Industrial da Gandra, 4805-017 Barco, Guimarães, Portugal.
J Mater Chem B. 2020 Jul 15;8(27):5928-5937. doi: 10.1039/d0tb00877j.
Cell-based therapies delivered via intrathecal injection are considered as one of the most promising solutions for the treatment of amyotrophic lateral sclerosis (ALS). Herein, injectable manganese-based biocompatible hydrogel blends were developed, that can allow image-guided cell delivery. The hydrogels can also provide physical support for cells during injection, and at the intrathecal space after transplantation, while assuring cell survival. In this regard, different formulations of methacrylated gellan gum/hyaluronic acid hydrogel blends (GG-MA/HA) were considered as a vehicle for cell delivery. The hydrogels blends were supplemented with paramagnetic Mn2+ to allow a real-time monitorization of hydrogel deposition via T1-weighted magnetic resonance imaging (MRI). The developed hydrogels were easily extruded and formed a stable fiber upon injection into the cerebrospinal fluid. Hydrogels prepared with a 75 : 25 GG-MA to HA ratio supplemented with MnCl2 at 0.1 mM showed controlled hydrogel degradation, suitable permeability, and a distinct MRI signal in vitro and in vivo. Additionally, human-derived adipose stem cells encapsulated in 75 : 25 GG-MA/HA hydrogels remained viable for up to 14 days of culture in vitro. Therefore, the engineered hydrogels can be an excellent tool for injectable image-guided cell delivery approaches.
鞘内注射的基于细胞的疗法被认为是治疗肌萎缩侧索硬化症（ALS）的最有前途的方法之一。在此，开发了可注射的基于锰的生物相容性水凝胶混合物，可实现图像引导的细胞递送。这些水凝胶在注射过程中也可为细胞提供物理支撑，在移植到鞘内空间后，还能确保细胞存活。在这方面，不同配方的甲基丙烯酰化凝胶多糖/透明质酸水凝胶混合物（GG-MA/HA）被认为是细胞递送的载体。将水凝胶混合物补充了顺磁性 Mn2+，以便通过 T1 加权磁共振成像（MRI）实时监测水凝胶沉积。所开发的水凝胶易于挤出，并在注入脑脊液后形成稳定的纤维。在 0.1mM 的 MnCl2 存在下，75：25 GG-MA 到 HA 的比例制备的水凝胶显示出可控的水凝胶降解、合适的渗透性和明显的体外和体内 MRI 信号。此外，封装在 75：25 GG-MA/HA 水凝胶中的人源脂肪干细胞在体外培养长达 14 天仍保持存活。因此，工程水凝胶可以成为用于可注射的图像引导细胞递送方法的优秀工具。
