A Modular Perfusion Bioreactor Platform for Simulating Bone Regeneration and Fracture Healing: Integrating Mechanical Loading and Dual Perfusion for Advanced In Vitro Models.

Recent advancements in tissue engineering have led to sophisticated in vitro models that better replicate physiological conditions. Bone regeneration remains a key research area due to its complex remodeling and biomechanical properties. Traditional models often fail to capture these dynamics, limiting their translational potential. Here, a modular bioreactor platform designed to simulate bone homeostasis and disease states with integrated mechanical load simulation is presented, featuring a 3D-printed microfluidic chamber, dynamic dual perfusion, and a mechanical compression device, enabling precise control of environmental parameters via a web interface. Applied to an in vitro fracture healing model, the setup prolonged viability by facilitating the inflammatory-to-anti-inflammatory transition. Additionally, the setup allowed for generating functional bone models through controlled mechanical stimulation, revealing mechanobiological insights. The dual perfusion approach further enhanced composite tissue incubation. This system advances in vitro tissue modeling by combining perfusion with mechanical stimulation, improving nutrient delivery, mechanotransduction, and scalability. It holds promise for preclinical research, drug testing, and regenerative medicine, bridging the gap between static in vitro models and physiologically relevant conditions.