Organ-on-a-chip development: a new model for muscular diseases testing
The principal aim of this project is to introduce students in the development of a muscle-on-a-chip. They will be involved in the fabrication of 3D muscle-like tissues. In parallel, they will develop a microfluidic chip platform to host the 3D tissue and use it as a more realistic and controlled in vitro model.
Our motivation to create a muscle-on-a chip is because muscular diseases affect millions of individuals each year (Duchenne muscular dystrophy shows an enormous impact of 1 incidence in 3300 live births), causing muscle atrophy, weakness and/or pain, producing muscle fiber degeneration, impairment of mobility and even premature death.
In the fight against muscular dystrophy the pharmaceutical industry relies heavily on in vivo animal models and in vitro two-dimensional (2D) cell cultures to develop therapeutic strategies. The problem is the pack of limitations associated with current in vivo and in vitro models. This is exemplified by the significant number of new drug candidates that fail to make it to market owing to low efficiency or severe side effects. These shortcomings are accompanied with regulatory restrictions limiting the use of animal models. Attempts to solve it have generated interest in developing human-based tissue-like constructs called organ-on-a-chip for disease modeling and drug and chemical testing.
Current in vitro research has focused on the development of organ/tissue-on-a-chip platforms capable of evaluate physiological parameters such as cell differentiation, tissue formation and contractibility. Nowadays, due to their biological and physiological relevance these devices represent a viable platform for personalized medicine and drug screening, looking for an efficient treatment for muscular diseases such as dystrophia.
Our approach relies on the fabrication of a three-dimensional muscle-like tissue, engineered in a microfluidic chip platform. Firstly, muscle cells are encapsulated in a biomaterial to obtain 3D scaffolds that mimic muscle structural organization. These 3D constructs would facilitate growth, alignment and differentiation muscle cells. Material composition, architecture, and cell density determine the proper muscle differentiation. It is necessary to review the fabrication process of these cell-laden biomaterials and testing the capability of these scaffolds to promote muscle differentiation.
On the other hand, soft lithography techniques are used to develop microfluidic chip devices. These chip platforms will host the tissue construct in chambers specially designed for this, and will allow the interchange of nutrients, controlling in an accurate way the cell medium flow rate.
Today organ-on-chip technologies represent a good alternative to the normal drug screening procedure and together with other technologies, as biosensing devices for example, could represent the best configuration to study deeply diseases related with the human organs.
Biology, Chemistry, Bioengineering, Biotechnology
Lab coat, laptop