Tumoricidal neural stem cells (NSCs) are an emerging therapy to combat glioblastoma (GBM). This therapy employs genetically engineered NSCs that secrete tumoricidal agents to seek out and kill tumor foci remaining after GBM surgical resection. Biomaterial scaffolds have previously been utilized to deliver NSCs to the resection cavity. Here, we investigated the impact of scaffold degradation rate on NSC persistence in the brain resection cavity. Composite acetalated dextran (Ace-DEX) gelatin electrospun scaffolds were fabricated with two distinct degradation profiles created by changing the ratio of cyclic to acyclic acetal coverage of Ace-DEX. In vitro, fast degrading scaffolds were fully degraded by one week, whereas slow degrading scaffolds had a half-life of >56 days. The scaffolds also retained distinct degradation profiles in vivo. Two different NSC lines readily adhered to and remained viable on Ace-DEX gelatin scaffolds, in vitro. Therapeutic NSCs secreting tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) had the same TRAIL output as tissue culture treated polystyrene (TCPS) when seeded on both scaffolds. Furthermore, secreted TRAIL was found to be highly potent against the human derived GBM cell line, GBM8, in vitro. Firefly luciferase expressing NSCs were seeded on scaffolds, implanted in a surgical resection cavity and their persistence in the brain was monitored by bioluminescent imaging (BLI). NSC loaded scaffolds were compared to a direct injection (DI) of NSCs in suspension, which is the current clinical approach to NSC therapy for GBM. Fast and slow degrading scaffolds enhanced NSC implantation efficiency 2.87 and 3.08-fold over DI, respectively. Interestingly, scaffold degradation profile did not significantly impact NSC persistence. However, persistence and long-term survival of NSCs was significantly greater for both scaffolds compared to DI, with scaffold implanted NSCs still detected by BLI at day 120 in most mice. Overall, these results highlight the benefit of utilizing a scaffold for application of tumoricidal NSC therapy for GBM.

杀肿瘤神经干细胞（NSC）是一种对抗胶质母细胞瘤（GBM）的新兴疗法。该疗法采用基因工程NSCs分泌杀肿瘤剂来寻找并杀死GBM手术切除后残留的肿瘤灶。生物材料支架以前曾被用来将 NSC 输送到切除腔。在这里，我们研究了支架降解率对脑切除腔内 NSC 持久性的影响。复合乙缩醛右旋糖酐 (Ace-DEX) 明胶电纺支架的制备具有两种不同的降解曲线，这是通过改变 Ace-DEX 的环状与非环状乙缩醛覆盖率的比率而产生的。体外，快速降解的支架在一周内完全降解，而缓慢降解的支架的半衰期> 56天。该支架还在体内保留了独特的降解特征。体外，两种不同的 NSC 系很容易粘附在 Ace-DEX 明胶支架上并保持活力。当接种在两个支架上时，分泌肿瘤坏死因子相关凋亡诱导配体（TRAIL）的治疗性 NSC 具有与组织培养处理的聚苯乙烯（TCPS）相同的 TRAIL 输出。此外，在体外，分泌的 TRAIL 被发现对人源 GBM 细胞系 GBM8 非常有效。将表达萤火虫荧光素酶的 NSC 接种在支架上，植入手术切除腔中，并通过生物发光成像 (BLI) 监测它们在大脑中的持久性。将负载 NSC 的支架与直接注射 (DI) 悬浮液 NSC 进行比较，后者是目前治疗 GBM 的 NSC 临床方法。快速和慢速降解支架使 NSC 植入效率分别比 DI 提高 2.87 倍和 3.08 倍。有趣的是，支架降解情况并没有显着影响 NSC 的持久性。然而，与 DI 相比，两种支架的 NSC 持久性和长期存活率显着更高，在大多数小鼠中，第 120 天时 BLI 仍然检测到支架植入的 NSC。总体而言，这些结果凸显了利用支架对 GBM 进行杀肿瘤 NSC 疗法的好处。