INVESTIGATING OPTOGENETICS AS AN APPROACH TO CONTROL GROWTH FACTOR EXPRESSION FOR TISSUE ENGINEERING

[摘要] The body exhibits a robust capacity for regeneration when faced with tissue injury or damage. In some cases, however, these insults can exceed the innate capacity for healing, resulting in permanent loss of structure and function. It is in these injuries where tissue engineering seeks to design interventions that can restore structure and function through the implementation of scaffolds, bioactive factors, and/or cells. Bioactive proteins have demonstrated immense efficacy in inducing tissue formation, but the administration of these factors has seen limitations that prevent them from seeing clinical success. Namely, precise spatiotemporal delivery of these factors is critical to their function and has yet to be achieved through exogenous delivery methods. There is thus a need for technologies that enable precise spatiotemporal administration of growth factors for tissue engineering. To this end, we propose that the precisely tunable variables associated with light make it an ideal stimulus for growth factor administration. Specifically, we sought to explore two previously developed light responsive systems as tools for controllable growth factor expression in mammalian cells with our overall goal being to make a case for optogenetic tools for tissue engineering applications. First, we explored the functionality of a red light-inducible adeno-associated virus (AAV). We next investigated a near infrared (NIR) optically responsive transcription control system as tool for tuned growth factor delivery. Finally, we ran preliminary studies to explore the feasibility of working with optogenetic systems in three dimensions (3D) through characterization of the relationship between scaffold fabrication parameters and light absorbance. In all, we validated tools for optogenetic control of growth factor expression and demonstrated feasibility of the technique for growth factor delivery in tissue engineering.

[发布机构] Rice University

[效力级别] biology