Nanocellulose-collagen composites as advanced biomaterials for 3D in-vitro neuronal model systems

Studying brain diseases and developing therapies requires versatile in vitro systems for long-term neuronal cultures. SH-SY5Y neuroblastoma cells are ideal for modeling neurodegenerative diseases. Although SH-SY5Y cells are commonly used in 2D cultures, 3D systems offer more physiologically relevant models. Studies have shown 3D culturing up to 7 days, but a simple, reproducible, and tunable system has yet to be identified. Cellulose holds potential to fulfill these needs. Cellulose and its derivatives are sustainable, cytocompatible, and ideal for synthesizing biocompatible hydrogels. Its abundance and ease of chemical modification make it a highly attractive biomaterial. This study explored nanocellulose-based hydrogels for promoting neuronal growth and morphogenesis. To enhance cell adhesion, a small amount of collagen was added to the hydrogel, and the resulting cell morphologies were analyzed and compared with those cultured in collagen and Matrigel. By chemically oxidizing cellulose and adjusting the blend, we developed composites that maintained neuronal viability for over 14 days in 3D cultures. Our findings show that nanocellulose-collagen composites offer superior cytocompatibility, promoting neuronal viability and neurite outgrowth more effectively than Matrigel and collagen. These tunable biomaterials support long-term 3D neuronal cultures, making them valuable for creating standardized models for disease research and drug development.