Engineering Sensory Ganglion Multicellular System to Model Tissue Nerve Ingrowth

Area of Science:

• Biomedical Engineering
• Neuroscience
• Tissue Engineering

Background:

• Discogenic pain involves nerve ingrowth into the annulus fibrosus (AF) of the intervertebral disc (IVD).
• Understanding the interaction between AF and neurons is crucial for developing effective pain therapies.

Purpose of the Study:

• To develop a novel in vitro model for studying nerve ingrowth into annulus fibrosus tissue.
• To investigate the neurotrophic and neurotropic effects of AF on nociceptor axons.
• To establish the role of anatomical proximity in AF-neuron crosstalk.

Main Methods:

• Primary bovine dorsal root ganglion (DRG) micro-scale tissue units were organized around AF explants within a collagen matrix using hydrodynamic forces.
• A multicellular system was engineered to mimic native DRG morphology and control AF-neuron distance.
• Pro-inflammatory cytokine-primed AF was used to assess its effects on nociceptor axons.

Main Results:

• The engineered system successfully mimicked native tissue morphology and established controlled AF-neuron distances.
• Primed AF exhibited neurotrophic and neurotropic effects on nociceptor axons.
• These effects were found to be dependent on the AF-neuron distance, highlighting the importance of anatomical proximity.

Conclusions:

• This study presents the first in vitro model using mature, large animal tissues to study AF nerve ingrowth in a physiologically relevant environment.
• The model recapitulates key aspects of AF-neuron interaction, essential for understanding discogenic pain.
• This biofabrication approach can be utilized to create multi-tissue/organ models for investigating pathophysiological conditions and advancing novel therapeutic strategies.