Safi Caroline, Solano Angela Giraldo, Liberelle Benoit, Therriault Hélène, Delattre Lisa, Abdelkhalek Melek, Wang Changsheng, Bergeron-Fortier Simon, Moreau Vaiana, De Crescenzo Gregory, Faucheux Nathalie, Lauzon Marc-Antoine, Paquette Benoit, Virgilio Nick
Research Center for High Performance Polymer and Composite Systems (CREPEC), Department of Chemical Engineering, Polytechnique Montréal, Montréal, Québec H3C 3A7, Canada.
Center for Research in Radiotherapy, Department of Nuclear Medicine and Radiobiology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Québec J1H 5N4, Canada.
ACS Appl Bio Mater. 2022 Aug 10. doi: 10.1021/acsabm.2c00598.
Glioblastoma multiforme is a type of brain cancer associated with a very low survival rate since a large number of cancer cells remain infiltrated in the brain despite the treatments currently available. This work presents a macroporous hydrogel trap, destined to be implanted in the surgical cavity following tumor resection and designed to attract and retain cancer cells, in order to eliminate them afterward with a lethal dose of stereotactic radiotherapy. The biocompatible hydrogel formulation comprises sodium alginate (SA) and chitosan (CHI) bearing complementary electrostatic charges and stabilizing the gels in saline and cell culture media, as compared to pristine SA gels. The highly controlled and interconnected porosity, characterized by X-ray microCT, yields mechanical properties comparable to those of brain tissues and allows F98 glioblastoma cells to penetrate the gels within the entire volume, as confirmed by fluorescence microscopy. The addition of a grafted -RGD peptide on SA, combined with CHI, significantly enhances the adhesion and retention of F98 cells within the gels. Overall, the best compromise between low proliferation and a high level of accumulation and retention of F98 cells was obtained with the hydrogel formulated with 1% SA and 0.2% CHI, without the -RGD adhesion peptide.
多形性胶质母细胞瘤是一种脑癌，其生存率极低，因为尽管有目前可用的治疗方法，但仍有大量癌细胞浸润在大脑中。这项工作展示了一种大孔水凝胶捕集器，它将在肿瘤切除后植入手术腔，旨在吸引并保留癌细胞，以便随后用致死剂量的立体定向放射疗法将其消除。与原始海藻酸钠（SA）凝胶相比，这种生物相容性水凝胶配方包含带有互补静电荷的海藻酸钠（SA）和壳聚糖（CHI），并能在盐水和细胞培养基中稳定凝胶。通过X射线显微CT表征的高度可控且相互连通的孔隙率产生了与脑组织相当的机械性能，并允许F98胶质母细胞瘤细胞在整个体积内穿透凝胶，这一点通过荧光显微镜得到了证实。在SA上添加接枝的-RGD肽并与CHI结合，可显著增强F98细胞在凝胶内的黏附与保留。总体而言，使用不含-RGD黏附肽的1% SA和0.2% CHI配制的水凝胶，在低增殖与F98细胞的高水平积累和保留之间实现了最佳平衡。
