Glioblastoma (GBM) is the most common primary malignant brain tumor diagnosed in adults, carrying with it an extremely poor prognosis and limited options for effective treatment. Various cell therapies have emerged as promising candidates for GBM treatment but fail in the clinic due to poor tumor trafficking, poor transplantation efficiency, and high systemic toxicity. In this study, we design, characterize, and test a 3D‐printed cell delivery platform that can enhance the survival of therapeutic cells implanted in the GBM resection cavity. Using continuous liquid interface production (CLIP) to generate a biocompatible 3D hydrogel, we demonstrate that we can effectively seed neural stem cells (NSCs) onto the surface of the hydrogel, and that the cells can proliferate to high densities when cultured for 14 days in vitro. We show that NSCs seeded on CLIP scaffolds persist longer than freely injected cells in vivo, proliferating to 20% higher than their original density in 6 days after implantation. Finally, we demonstrate that therapeutic fibroblasts seeded on CLIP more effectively suppress tumor growth and extend survival in a mouse model of LN229 GBM resection compared to the scaffold or therapeutic cells alone. These promising results demonstrate the potential to leverage CLIP to design hydrogels with various features to control the delivery of different types of cell therapies. Future work will include a more thorough evaluation of the immunological response to the material and improvement of the printing resolution for biocompatible aqueous resins.

中文翻译：

---

使用连续液体界面生产开发生物相容性 3D 水凝胶支架，用于递送细胞疗法以治疗复发性胶质母细胞瘤


胶质母细胞瘤 （GBM） 是成人中最常见的原发性恶性脑肿瘤，预后极差，有效治疗选择有限。各种细胞疗法已成为 GBM 治疗的有前途的候选者，但由于肿瘤运输不良、移植效率低和全身毒性高而在临床上失败。在这项研究中，我们设计、表征和测试了一个 3D 打印的细胞递送平台，该平台可以提高植入 GBM 切除腔的治疗细胞的存活率。使用连续液体界面生产 （CLIP） 生成生物相容性 3D 水凝胶，我们证明我们可以有效地将神经干细胞 （NSC） 接种到水凝胶表面，并且细胞在体外培养 14 天后可以增殖至高密度。我们表明，接种在 CLIP 支架上的 NSCs 比体内自由注射的细胞持续更长时间，在植入后 6 天内增殖至比其原始密度高 20%。最后，我们证明，与单独的支架或治疗性细胞相比，接种在 CLIP 上的治疗性成纤维细胞在 LN229 GBM 切除术的小鼠模型中更有效地抑制肿瘤生长并延长生存期。这些有希望的结果表明，利用 CLIP 设计具有各种功能的水凝胶以控制不同类型细胞疗法的递送的潜力。未来的工作将包括更彻底地评估对材料的免疫反应，以及提高生物相容性水性树脂的打印分辨率。