Project Overview

We propose to develop chemically defined synthetic extracellular matrices to support neural cells in longterm
stable cell culture. Human induced pluripotent stem cells (hiPSCs) have revolutionized disease
modeling and drug discovery. Enhanced 2D and 3D culture models have tremendous potential to enable
hiPSC development with greater cellular maturity compared to conventional 2D cultures. Enhanced cell
culture models promote cellular self-organization reminiscent of the organization of human neural tissue.
Increased cellular maturity and complexity better reflect the diverse neural cell types and interactions in the
central nervous system, to support the challenge of modeling maturity in neurodegenerative diseases.

Challenge: Contemporary hiPSC 2D and 3D cell cultures heavily depend on Matrigel®, a complex
extracellular matrix extracted from the Engelbreth-Holm-Swarm (EHS) mouse sarcoma cell line. Matrigel®
suffers from serious batch-to-batch variability and supply shortages. A xeno-free chemically defined
synthetic alternative could replace Matrigel® with a defined and reproducible matrix for hiPSCs, enabling
standardized and reliable experimental conditions.

Solution: Professor Kennedy’s group has developed a matrix based on the synthetic biocompatible
polymer dendritic polyglycerol amine (dPGA) that is now marketed by the Quebec-based company
Dendrotek Biosciences Inc. hiPSC derived neurons grown on dPGA exhibit enhanced survival,
differentiation, and can be maintained for substantially longer periods in vitro. dPGA amines readily support
chemical modification to enhance function and incorporation into 3D hydrogels with tunable characteristics
and defined ligand presentation.

Deliverables: We will enhance functionality by chemically modifying dPGA. Neural cells will be tested on
2D substrates and modulus optimized poly-electrolyte multilayers that incorporate modified dPGA. 3D
hydrogels will be engineered for hiPSC culture and neural organoids. Optimized hydrogel formulations,
comprehensive characterization data, and considerations for scaling up and manufacturing will be identified.

Impact: We aim to advance the hiPSC field by enabling the development of innovative applications in
regenerative medicine, disease modeling, and drug discovery.

Principal Investigator

Timothy E. Kennedy , McGill University

Team Members

Chris Barrett, McMaster University

Jayachandran Kizhakkedathu, University of British Columbia

Linda Reven, McGill University

Thomas Durcan, Montreal Neurological Institute and Hospital, McGill University

Partners and Donors

CQDM

DendroTEK Biosciences Inc