Toward bioengineered muscle-fat microphysiological systems for sports medicine and obesity therapeutics

Muscle injuries represent a major healthcare burden, yet we lack platforms capable of predicting human responses to exercise, injury, and therapeutic interventions. Muscle-on-chip (MoC) technologies can now reproduce physiological force generation, electrical activity, and repair processes. However, most existing systems still culture muscle in isolation, limiting their ability to capture physiological interactions. Such models overlook the bidirectional signaling between muscle and adipose tissue that regulates exercise performance and metabolic balance. Myokines released during exercise promote adipose lipolysis and browning, whereas adipokines associated with obesity can hinder muscle function and regeneration. Over the past two decades, microphysiological systems (MPS) have evolved from simple passive microfluidic channels into dynamic, responsive platforms that capture muscle contraction forces, cytokine secretion, and electrical responses in real time. An integrated muscle-adipose platform that preserves distinct culture environments and allows controlled cytokine exchange is still lacking. Beyond integration challenges, we highlight critical gaps in tissue maturation, standardization, neuromuscular innervation, and scalability. This review focuses on current skeletal muscle-on-chip technologies, emerging adipose-relevant modeling strategies, and the design requirements needed to build future integrated muscle-adipose microphysiological systems for sports medicine and obesity therapeutics.