Summary of the original aims and objectives 

This project aims to develop a material with improved blood compatibility for use in cardiovascular biomedical device applications. Current cardiovascular biomaterials initiate blood coagulation, and the accumulation of the blood clot can lead to failure of devices such as small diameter vascular grafts and artificial heart valves. This is both life threatening to the patient and costly to society. We proposed to develop new polymeric materials that work with biology to result in improved healing by utilizing advanced polymer chemistry and organic chemistry techniques in order to incorporate cutting edge knowledge from the field of cell biology into a synthetic platform. Specifically, the materials developed in this project will improve the adhesion and function of endothelial cells, as it is these cells that generate the blood compatibility of native vasculature.  

Progress made during the year against these objectives, including notable results and findings

We used RAFT polymerization to generate a copolymer of methyl methacrylate and polyethylene glycol methacrylate. The material is water stable allowing for in vivo applications, and the material is resistant to the  deposition of proteins from the solution phase which has been shown to result in undesired cellular attachment and inflammation. We have illustrated that these materials are resistant to protein adsorption and the subsequent cellular attachment that this would result in.

These materials act as a blank slate on which we can build specific biofunctionality through the incorporation of peptide ligands. These ligands then bind specific cell receptors present on the endothelial cell surface. The biomaterials have been shown to result in specific adhesion, spreading, and proliferation of the endothelial cells in vitro. Furthermore, we can control the degree of endothelial cell adhesion by tailoring the concentration of peptide within the material.

We are currently producing materials that display nanoscale clusters of these ligands as the nanoscale presentation will promote several advantageous cell behaviours including stronger cellular adhesion, improved migration, increased proliferation, and endothelial cell specific phenotype.

Scholarly outcomes, including titles of publications, conference publications, etc

 O’Connor AJ, Marre D, Yap KK, Heath DE, Morrison WA. Tissue Engineering. Chapter 16 In Plastic Surgery,

4th ed.; Vol. 1: Principles. Gurtner GC, Ed. Elsevier Inc.: Amsterdam. (Accepted 8 March 2016)

Heath DE, Kang GCW, Cao Y, Poon YF, Chan V, Chan-Park MBE. Biomaterials Patterned with Discontinuous Microwalls for Vascular Smooth Muscle Cell Culture: Biodegradable Small Diameter Vascular Grafts and Stable Cell Culture Substrates.Journal of Biomedical Materials Research, Polymer Edition. (Under review)

Shirbin SJ, Karimi F, Chan NJA, Heath DE, Qiao GG. Macroporous Hydrogels composed Entirely of Synthetic Peptides: Biocompatible and Enzyme Biodegradable 3D Cellular Scaffolds. Biomacromolecules. (Under review)

Kusuma GD, Brennecke SP, O’Connor AJ, Kalionis B, Heath DE. Cell lines can produce large quantities of extracellular matrix for improved expansion of primary mesenchymal stem cells. Acta Biomaterialia. (Under review)

Karimi F, O’Connor AJ, Qiao G, Heath DH. Advanced Biomaterials to Promote Endothelialization. Australasian Polymer Symposium. (Under review)