Diabetes is the most prevalent and epidemic metabolic disorder throughout the world. Type 2 diabetes (T2D) is the most common form characterized by hyperinsulinemia and insulin resistance. The maintenance of normal glucose homeostasis depends on a finely balanced dynamic interaction between skeletal muscle sensitivity to insulin and insulin secretion. Thus, the evolution of T2D requires the presence of defects in both insulin secretion and insulin action, and it requires the simultaneous study of both tissues, which results in complex, expensive and time consuming with conventional methods.
The pharmaceutical industry relies heavily on in vivo animal models and in vitro two-dimensional (2D) cell cultures to develop therapeutic strategies. There are many ethical issues surrounding animal studies, and serious concerns also exist regarding their biological relevance to humans. Current in vitro tissues are also helpful for studying the molecular and cellular basis of physiological and pathological responses of biological processes. However, due to their 2D structure, they do not consider the complexity of the physiological microenvironment in which cells grow. There is, thus, growing interest in developing fully functional three-dimensional (3D) tissues.
DAMOC aims to overcome these limitations in a revolutionary technological approach that allows us to engineer skeletal muscle tissues and pancreatic islets in a multi-OOc to open new research areas on human T2D disease.
During DAMOC's execution period, we have accomplished all objectives. We have bioengineered a new in vitro model to mimic the insulin-mediated skeletal muscle glucose metabolism. To this aim, both muscle tissues and pancreatic islets have been fabricated, generated and combined in a multi-OOC approach to study pancreatic islets' insulin secretion and the associated glucose-induced contraction of muscle tissues. We have developed several biomaterials and protocols to encapsulate and maturate skeletal muscle cells and pancreatic pseudoislets. Engineered tissues have benefited from novel scaffolds and have been integrated into bioreactors, with an electrical stimulator and biosensors to monitor myokine secretion from skeletal muscle cells, insulin production, and effects of skeletal muscle contraction on beta-cells. In a multidisciplinary approach, we have used micro- and nanoscale fabrication technologies developed by our research group, and we have integrated novel biosensing technology to monitor metabolic processes relevant to diabetes, such as myokines release. This multi-OOC is an important enabling step for diabetes modelling, the study of insulin resistance, and the investigation of drug candidates for therapy, usually performed by long-time and expensive animal experiments.
