Advancing tendon-to-bone enthesis repair: from biomimetic materials to microRNA modulation

The insertion between tendons and bones is called enthesis. Injuries at the enthesis account for a significant proportion of all sport-related injuries. Additionally, sedentarism, obesity, and ageing are risk factors for enthesis injuries. The enthesis does not heal properly, and the regeneration of the native morphology of this tissue after injury constitutes an unmet challenge for tissue engineers. This thesis is focused on researching potential tissue engineering approaches to aid the process of enthesis healing by exploring the use of biomimetic biomaterials and novel molecular tools to enhance the quality of healing upon injury. This thesis describes the use of biomimetic silk-fibroin scaffolds with an enthesis-like morphology to yield better enthesis healing upon injury in a rodent animal model. Additionally, this thesis investigated the patterns of expression of an interesting class of molecules known as miRNAs during the early stages of enthesis healing. miRNAs have the potential to regulate the process of healing and fibrosis. A set of at least 13 miRNAs were hereby identified as relevant for enthesis healing. Moreover, miRNA-16-5p was evaluated in vitro for its potential therapeutic use to regulate the occurrence of fibrosis and scar tissue.