I-Corps: Synthetic Matrix Solutions for Neurodegenerative Disease Platforms

Massachusetts Institute Of Technology, Cambridge MA

Investigators

Abstract

The broader impact/commercial potential of this I-Corps project is to improve neural cell culture assays, thus furthering the research and development of treatments for neurodegenerative diseases. To enable the development of new therapies, there is a need for better functional control of long-term, physiologically relevant in vitro models that are translatable to the clinic and ultimately increase treatment efficacy and mitigate patient risk. While many components are necessary for a physiologically relevant model, one key area of concern is the substrate upon which neural cells are grown. In vitro cell culture platforms using substrates such as matrigel and recombinant human laminin can result in aggregation and delamination of cultured neurons within a week. The synthetic polymer substrate we are developing is designed to promote neural cell attachment and reduce delamination, enabling long-term culture and functional analysis of the cells. Furthermore, a defined substrate formulation is desirable for maintaining cell culture consistency that is expected to yield more homogenous neural cell populations, which is an advantage over animal-derived substrates. This I-Corps project will focus on the commercial potential of novel synthetic polymers upon which neural progenitor cells (NPCs) can grow, expand, and differentiate into neural cell lineages. The proposed product is expected to enable enhanced neural cell attachment, while maintaining viability and functionality for long-term cell culture applications. The synthetic substrate is a poly(ethylene) glycol (PEG)-based polymer that can be mechanically modulated to alter its physical properties. Additionally, bioactive modifications that mimic the native cellular microenvironment can be incorporated to enhance functionality. A key feature of this polymer is that chemical and mechanical properties are preserved across different synthesis protocols, significantly reducing the risk of batch-to-batch variability, which is a major concern with commercially available natural substrates such as matrigel. The synthetic polymer system has previously been used to enhance the attachment of other stem cell-derived cultures such as endothelial cells and preliminary data suggest that it will support stem cell-derived NPC culture. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.