Neural cell responses to spinal implant biomaterials in a 3D-bioprinted cell culture model

Abstract

Spinal implants are vital for treating spinal disorders, yet wear particle-induced complications threaten their long-term success. Despite this, the direct effects of implant-derived particles on neural cells remain largely unexplored, especially given the limitations of conventional 2D culture models to capture such complex interactions. The current study introduces a novel in vitro platform consisting of a 3D-bioprinted gelatin methacryloyl (GelMA) hydrogel embedded with neural cells (C6 astrocyte-like and NG108-15 neurons) and spinal implant biomaterial particles, designed to model the spinal cord microenvironment with enhanced physiological relevance. As the first of its kind, this cell-particle-laden system supports the evaluation of neural cell responses to spinal biomaterial particles, including polymers, PEEK-OPTIMA™ and polyethylene Ceridust® 3615, zirconia-toughened alumina (ZTA) ceramic, and CoCrMo metal alloy. The bioprinted platform demonstrated excellent compatibility with various neural cell types and particle compositions, enabling a wide range of biological assays. Cell viability within the 3D model was comparable to traditional 2D cultures, affirming its ability to sustain cell survival while offering improved biomimicry. Biological assays assessing cell viability, reactive oxygen species (ROS) production, and DNA damage provided critical insights into material-specific and time-dependent cellular responses. While no significant cytotoxic effects were observed in short-term cultures, distinct variations in ROS production, and viability emerged based on biomaterial type and exposure duration. Overall, this versatile 3D-bioprinted system presents a robust, scalable tool for mechanistic and toxicological studies of spinal implant wear particles under physiologically relevant conditions.

Keywords

3D model / Biomaterial particles / Bioprinting / C6 Astrocyte-like cells / Cell viability / Nevural cells / NG108-15 cells / Reactive oxygen species