Engineering Sensory Ganglion Multicellular System to Model Tissue Nerve Ingrowth

Abstract Discogenic pain is associated with deep nerve ingrowth in annulus fibrosus tissue (AF) of intervertebral disc (IVD). To model AF nerve ingrowth, primary bovine dorsal root ganglion (DRG) micro‐scale tissue units are spatially organised around an AF explant by mild hydrodynamic forces within...

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Main Authors: Junxuan Ma, Janick Eglauf, Sibylle Grad, Mauro Alini, Tiziano Serra
Format: Article
Language:English
Published: Wiley 2024-03-01
Series:Advanced Science
Subjects:
Online Access:https://doi.org/10.1002/advs.202308478
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author Junxuan Ma
Janick Eglauf
Sibylle Grad
Mauro Alini
Tiziano Serra
author_facet Junxuan Ma
Janick Eglauf
Sibylle Grad
Mauro Alini
Tiziano Serra
author_sort Junxuan Ma
collection DOAJ
description Abstract Discogenic pain is associated with deep nerve ingrowth in annulus fibrosus tissue (AF) of intervertebral disc (IVD). To model AF nerve ingrowth, primary bovine dorsal root ganglion (DRG) micro‐scale tissue units are spatially organised around an AF explant by mild hydrodynamic forces within a collagen matrix. This results in a densely packed multicellular system mimicking the native DRG tissue morphology and a controlled AF‐neuron distance. Such a multicellular organisation is essential to evolve populational‐level cellular functions and in vivo‐like morphologies. Pro‐inflammatory cytokine‐primed AF demonstrates its neurotrophic and neurotropic effects on nociceptor axons. Both effects are dependent on the AF‐neuron distance underpinning the role of recapitulating inter‐tissue/organ anatomical proximity when investigating their crosstalk. This is the first in vitro model studying AF nerve ingrowth by engineering mature and large animal tissues in a morphologically and physiologically relevant environment. The new approach can be used to biofabricate multi‐tissue/organ models for untangling pathophysiological conditions and develop novel therapies.
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spelling doaj.art-63db4b9bb14e43dd8bc623c545f703862024-03-20T12:56:12ZengWileyAdvanced Science2198-38442024-03-011111n/an/a10.1002/advs.202308478Engineering Sensory Ganglion Multicellular System to Model Tissue Nerve IngrowthJunxuan Ma0Janick Eglauf1Sibylle Grad2Mauro Alini3Tiziano Serra4AO Research Institute Clavadelerstrasse 8 Davos 7270 SwitzerlandAO Research Institute Clavadelerstrasse 8 Davos 7270 SwitzerlandAO Research Institute Clavadelerstrasse 8 Davos 7270 SwitzerlandAO Research Institute Clavadelerstrasse 8 Davos 7270 SwitzerlandAO Research Institute Clavadelerstrasse 8 Davos 7270 SwitzerlandAbstract Discogenic pain is associated with deep nerve ingrowth in annulus fibrosus tissue (AF) of intervertebral disc (IVD). To model AF nerve ingrowth, primary bovine dorsal root ganglion (DRG) micro‐scale tissue units are spatially organised around an AF explant by mild hydrodynamic forces within a collagen matrix. This results in a densely packed multicellular system mimicking the native DRG tissue morphology and a controlled AF‐neuron distance. Such a multicellular organisation is essential to evolve populational‐level cellular functions and in vivo‐like morphologies. Pro‐inflammatory cytokine‐primed AF demonstrates its neurotrophic and neurotropic effects on nociceptor axons. Both effects are dependent on the AF‐neuron distance underpinning the role of recapitulating inter‐tissue/organ anatomical proximity when investigating their crosstalk. This is the first in vitro model studying AF nerve ingrowth by engineering mature and large animal tissues in a morphologically and physiologically relevant environment. The new approach can be used to biofabricate multi‐tissue/organ models for untangling pathophysiological conditions and develop novel therapies.https://doi.org/10.1002/advs.202308478acoustic assemblyadvanced in vitro modelsalternatives to animal testingmulticellular systemsensory nerve ingrowth
spellingShingle Junxuan Ma
Janick Eglauf
Sibylle Grad
Mauro Alini
Tiziano Serra
Engineering Sensory Ganglion Multicellular System to Model Tissue Nerve Ingrowth
Advanced Science
acoustic assembly
advanced in vitro models
alternatives to animal testing
multicellular system
sensory nerve ingrowth
title Engineering Sensory Ganglion Multicellular System to Model Tissue Nerve Ingrowth
title_full Engineering Sensory Ganglion Multicellular System to Model Tissue Nerve Ingrowth
title_fullStr Engineering Sensory Ganglion Multicellular System to Model Tissue Nerve Ingrowth
title_full_unstemmed Engineering Sensory Ganglion Multicellular System to Model Tissue Nerve Ingrowth
title_short Engineering Sensory Ganglion Multicellular System to Model Tissue Nerve Ingrowth
title_sort engineering sensory ganglion multicellular system to model tissue nerve ingrowth
topic acoustic assembly
advanced in vitro models
alternatives to animal testing
multicellular system
sensory nerve ingrowth
url https://doi.org/10.1002/advs.202308478
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AT sibyllegrad engineeringsensoryganglionmulticellularsystemtomodeltissuenerveingrowth
AT mauroalini engineeringsensoryganglionmulticellularsystemtomodeltissuenerveingrowth
AT tizianoserra engineeringsensoryganglionmulticellularsystemtomodeltissuenerveingrowth