Cooper-White, JJ1,2,3,*

 

1Australian Institute for Bioengineering & Nanotechnology, The University of Queensland, St. Lucia, QLD 4072, AUSTRALIA.
2
School of Chemical Engineering, The University of Queensland, St. Lucia, QLD 4072, AUSTRALIA.
3Biomedical Manufacturing, Manufacturing Flagship, CSIRO, Clayton, Victoria 3169, AUSTRALIA.

 

Delivery of mesenchymal or perivascular stem cells (M/pvSCs), whether they be derived from adult tissues or more recently from induced Pluripotent Stem Cells, have significant potential to revolutionize medicine. However, mounting evidence suggests that whilst delivering these cells modulates the local immune response and can enhance healing, very few of the delivered cells actually participate in local tissue regeneration. There is a dire need for biomaterial substrates and scaffolds that can be tailored to not only deliver stem cells, but to also impart directive cues to such cells to encourage effective tissue generation and repair at the site of injury. Over the last number of years, we have focused on developing tailored substrates and scaffolds to probe the impacts of substrate viscoelasticity, ligand type, and ligand lateral spacing on M/PSC fate choice, exemplifying that deterministic control over PSC behaviours is possible. Most recently, we have developed a new biomaterial system that permits a cell to remodel it’s microenvironment, through our hydrogel enabling capture and presentation of secreted extracellular proteins that in traditional hydrogels are rapidly lost from the local microenvironment due to diffusion. We show that through this capture, we can support and enhance M/pvSC differentiation to multiple lineages. Lastly, given the complexity of the stem cell niche microenvironment, we have recently developed a new method by which to create libraries of hundreds of new polymers in 10’s of minutes using high throughput (HTP) rapid one-pot sequential aqueous RAFT (rosa-RAFT). From these panels of new polymers,  we can now construct combinatorially 10’s to 100’s of thousands of stem cell microenvironments in hydrogel microparticles. Through HTP screens of stem cell potency maintenance and differentiation, we now have the ability to rapidly discover new biomaterials and identify novel effectors or cues capable of driving M/pvSC fate choice.