Dromel Pierre C, Singh Deepti, Andres Eliot, Likes Molly, Kurisawa Motoichi, Alexander-Katz Alfredo, Spector Myron, Young Michael
Massachusetts Institute of Technology, Cambridge, MA, USA.
Schepens Eye Research Institute of Massachusetts Eye and Ear, Harvard Medical School, Boston, MA, USA.
NPJ Regen Med. 2021 Dec 20;6(1):85. doi: 10.1038/s41536-021-00195-3.
Biomaterial-based cell replacement approaches to regenerative medicine are emerging as promising treatments for a wide array of profound clinical problems. Here we report an interpenetrating polymer network (IPN) composed of gelatin-hydroxyphenyl propionic acid and hyaluronic acid tyramine that is able to enhance intravitreal retinal cell therapy. By tuning our bioinspired hydrogel to mimic the vitreous chemical composition and mechanical characteristics we were able to improve in vitro and in vivo viability of human retinal ganglion cells (hRGC) incorporated into the IPN. In vivo vitreal injections of cell-bearing IPN in rats showed extensive attachment to the inner limiting membrane of the retina, improving with hydrogels stiffness. Engrafted hRGC displayed signs of regenerating processes along the optic nerve. Of note was the decrease in the immune cell response to hRGC delivered in the gel. The findings compel further translation of the gelatin-hyaluronic acid IPN for intravitreal cell therapy.
基于生物材料的细胞替代再生医学方法正在成为治疗一系列严重临床问题的有前景的治疗手段。在此，我们报告一种由明胶-羟苯基丙酸和透明质酸酪胺组成的互穿聚合物网络（IPN），它能够增强玻璃体内视网膜细胞治疗。通过调整我们受生物启发的水凝胶以模拟玻璃体的化学成分和机械特性，我们能够提高整合到IPN中的人视网膜神经节细胞（hRGC）在体外和体内的存活率。在大鼠体内进行含细胞IPN的玻璃体内注射显示，其与视网膜内界膜广泛附着，随着水凝胶硬度的增加而改善。移植的hRGC显示出沿视神经再生过程的迹象。值得注意的是，对凝胶中递送的hRGC的免疫细胞反应有所降低。这些发现促使明胶-透明质酸IPN在玻璃体内细胞治疗方面进一步转化应用。
