A Programmed Anti-Inflammatory Nanoscaffold (PAIN) as a 3D Tool to Understand the Brain Injury Response

Immunology is the next frontier of nano/biomaterial science research, with the immune system determining the degree of tissue repair. However, the complexity of the inflammatory response represents a significant challenge that is essential to understand for the development of future therapies. Cell-instructive 3D culture environments are critical to improve our understanding of the link between the behavior and morphology of inflammatory cells and to remodel their response to injury. This study has taken two recent high-profile innovations—functional peptide-based hydrogels, and the inclusion of anti-inflammatory agents via coassembly—to make a programmed anti-inflammatory nanoscaffold (PAIN) with unusual and valuable properties that allows tissue-independent switching of the inflammatory cascade. Here, extraordinary durability of the anti-inflammatory agent allows, for the first time, the development of a 3D culture system that maintains the growth and cytoskeletal reorganization of brain tissue, while also facilitating the trophic behavior of brain cells for 22 d in vitro. Notably, this behavior was confirmed within an active scar site due to the unprecedented resilience to the presence of inflammatory cells and enzymes in the brain. Efficacy of the culture system is demonstrated via novel insights about inflammatory cell behavior, which would be impossible to obtain via in vivo experimentation.