A 3D-bioprinted dermal-like scaffold incorporating fibroblasts and DRG neurons to investigate peripheral nerve regeneration†

Abstract

Peripheral nervous system (PNS) regeneration is a rapidly advancing field with critical implications for addressing sensory impairments and neuropathic conditions. Dorsal root ganglion (DRG) neurons, essential for sensory transmission, exhibit regenerative potential through axonal regeneration. However, the mechanisms driving these processes are not yet understood. This study introduces an innovative 3D-bioprinted fibroblasts/DRG co-culture construct, specifically designed to investigate and characterize PNS regeneration and wiring mechanisms under both physiological and pathophysiological conditions. By characterizing bioink rheology and optimizing bioprinting parameters, we created a stable, biocompatible derma-like construct supporting cell adhesion and growth. Bioprinted 3T3 fibroblasts demonstrate high viability and proliferation, while DRG neurons exhibit enhanced neurite outgrowth and complex branching patterns within the co-culture system. These findings highlight the role of fibroblasts in promoting axonal regeneration and provide a robust in vitro platform for studying sensory system reinnervation. This model lays the foundation for developing personalized therapies for neuropathic pain and sensory dysfunction, advancing both fundamental neuroscience and translational medicine.