Innervated Bone-on-a-Chip System for Mimicking Bone Remodelling

Abnormal bone remodeling occurs in diseases like osteoporosis and osteoarthritis, imposing significant burden on patients and society, leading to increased healthcare costs and productivity losses. This issue is expected to escalate with the rising prevalence of sedentary lifestyles and an aging population. Proper innervation is crucial for bone function, and disruptions in nerve function can severely impact remodeling. Despite its importance, interactions between sensory nerves, osteoblasts, and osteoclasts are often overlooked in bone tissue engineering research. Organ-on-a-chip technology provides a novel approach for developing in vitro bone remodeling models by creating distinct microenvironments for neurons and bone. This project aims to engineer a three-dimensional PDMS-based innervated bone-on-a-chip (BoC) model that incorporates natural bone scaffolds with osteoblasts, osteoclasts, and sensory neurons Osteoclastogenesis induced by exogenous (M-CSF+RANKL) and endogenous (PGE2+Vitamin D3) stimulation has been used to establish the in vitro bone remodeling model Innervation of the bone remodeling model has been achieved by seeding PC-12 neuron-like cells inside the nerve unit of the BoC. Abnormal bone remodeling was successfully induced by exogenously adding the pro-inflammatory factor IL-1β or excess dexamethasone. The established BoC model can provide critical insights into how altered sensory innervation influences bone remodeling and vice versa. Additionally, it has significant potential as a tool for evaluating the therapeutic efficacy of drugs targeting abnormal bone remodeling. The findings are expected to pave the way for innovative treatment strategies for skeletal disorders, improving patient outcomes and quality of life.