Micropathological Chip Modeling the Neurovascular Unit Response to Inflammatory Bone Condition

Area of Science:

• Biomedical Engineering
• Tissue Engineering
• Regenerative Medicine

Background:

• Organ-on-a-chip platforms offer advanced in vitro models for complex physiological and pathological processes.
• Bone diseases like osteoarthritis involve intricate interactions between inflammation, bone homeostasis, sensory innervation, and angiogenesis.
• Existing in vitro models lack the capability to simultaneously replicate the complexity of bone, vasculature, innervation, and inflammation.

Purpose of the Study:

• To develop a microfluidic-based neuro-vascularized bone chip (NVB chip) to model neurovascular network interactions within an inflammatory bone niche.
• To investigate the mechanistic interplay between innervation and angiogenesis in the context of inflammatory bone disease.
• To utilize the NVB chip as a screening tool for novel therapeutic strategies, including nano-based drug delivery systems, for inflammatory bone diseases.

Main Methods:

• Development of a microfluidic-based neuro-vascularized bone chip (NVB chip).
• Optimization of platform design and conditions to study the neurovascular network under inflammatory conditions.
• Validation of the NVB chip by delivering anti-inflammatory drug-loaded nanoparticles to modulate neuronal growth and pain perception.

Main Results:

• Successful establishment of a functional NVB chip capable of mimicking the neurovascular environment of bone under inflammation.
• Demonstration of the platform's ability to model mechanistic interactions between innervation and angiogenesis.
• Validation of the NVB chip's efficacy in delivering therapeutic nanoparticles to counteract inflammation-induced neuronal changes.

Conclusions:

• The developed NVB chip provides a reliable in vitro tool for understanding the bone neurovascular system.
• This platform can elucidate novel mechanisms underlying inflammatory bone diseases, bone destruction, and pain.
• The NVB chip opens new avenues for discovering and testing innovative therapies for bone-related inflammatory conditions.