Characterization of a Bioprinted Anticancer Cell Therapy System Generated with Continuous Liquid Interface Production

Abstract

Anticancer cell therapies have remarkable clinical potential yet fail to reach the clinic due to poor delivery. 3D bioprinting (3DBP) can be leveraged for generating cell therapy delivery devices, where the biomaterial system acts as a protective matrix to stabilize cells after implantation. Continuous liquid interface production (CLIP), an additive manufacturing technology, has several unique features that make it a suitable platform for 3DBP of cell-laden scaffolds. However, the feasibility CLIP bioprinting and efficacy of CLIP-bioprinted cell/matrix therapies have not yet been explored. In this work, we demonstrate the utility of CLIP for cell therapy 3DBP with a simple gelatin methacrylate-based resin and anticancer drug-secreting fibroblasts as a model therapy against recurrent glioblastoma. We demonstrate that CLIP enables rapid, consistent production of cell-laden scaffolds, and cells maintain their viability and tumor-killing efficacy in vitro post-printing. Importantly, we proved that bioprinted cells survive longer in vivo than directly injected cells, and that this effect may correspond to better survival outcomes in a mouse model of glioblastoma resection. This study is the first to utilize CLIP for 3DBP of composite devices containing anticancer cell therapies, providing a crucial foundation for developing highly refined cell therapy delivery devices in the future.