Tendon-on-a-chip: A biomimetic tendinopathy model

Tendon disease is one of the most prevalent orthopedic problems. As no current treatment can restore the functional qualities of injured tendons, a fibrotic scar and persistent tendinopathy commonly ensue, causing pain and high re-injury rate and reducing the mobility and quality of life of affected patients. Therefore, tendon problems place a significant burden on patients and society and provide a growing challenge to healthcare systems, with human tendon injuries accounting for more than 145 billion in yearly medical costs. Although the high and rising prevalence is motivating research efforts, scientific and clinical advances are hindered by the lack of valid models of tendon disease. Currently available in vitro models do not mimic the natural tendon environment and hence have limited relevance for the study of pathophysiological processes. Therefore, tendon research is commonly carried out in animal models in vivo with the abysmal translational success highlighting their inherent ethical, scientific, and clinical limitations and problems. Thus, pathophysiologically relevant models, which mimic the biological niche, including the three-dimensional extracellular matrix, the biomechanical forces naturally exerted on tendon tissue, and the interaction with immune cells during inflammation, are urgently needed. This project aims to replace animal models of tendinopathy with a 3D microfluidic model (tendon-on-a-chip) that mimics the multiaxial mechanical overload and the associated inflammatory response in both extrasynovial (e.g. Achilles tendon) and intrasynovial tendons (e.g. rotator cuff); This model will be uniquely suited to investigating the mechanobiology and short-term inflammatory cascades of tendon injury and will be able to replace a broad range of large and small animal models.