Three-Dimensional Graphene Microelectrode Arrays for Detection of Wound Healing Biomarkers

Volumetric muscle loss (VML) injuries, such as those from high-energy trauma or tumor ablation, often result in scar tissue formation and permanent loss of skeletomuscular function. Directly after VML injury formation, neutrophils and macrophages arrive at the wound site, releasing cytokines and growth factors to allow proliferation and innervation. Monitoring the wound healing process by spatially mapping key regulatory wound biomarkers, such as nitric oxide (NO), can elucidate the state of the wound and thus inform critical clinical interventions. While single-point NO probes with sufficient performance for short-term measurements have been produced previously, improvements in device sensitivity, stability, and the number of sensing nodes are needed for in vivo applications. Here we leverage novel nanomaterials and their exceptional electrochemical properties to construct three-dimensional fuzzy graphene (3DFG) microelectrode arrays (MEAs) for the multiplexed electrochemical sensing of NO. We report in vitro results for 3DFG MEAs capable of selectively detecting NO (versus known interferents such as nitrite, ascorbic acid, and uric acid) at physiological concentrations in the nanomolar regime (limit of detection < 10 nM). Future work will entail in vivo NO detection to aid in monitoring wound states in animal models.