Engineering bioartificial extracellular tumour microenvironments for Osteosarcoma personalised precision oncology

Overview

Osteosarcoma (OS) is the most common malignant bone tumour affecting children and adolescents. Importantly, clinical outcomes have not improved for decades, and bone tumours remain to be a leading cause of cancer-related death in adolescents.

By identifying ideal treatment approaches for each individual patient, precision oncology has the potential to significantly improve these outcomes. Yet, its widespread application is hindered by a lack of biomaterials that support the reproducible and robust generation of patient-derived osteosarcoma organoids in vitro.

Therefore, this project will develop tumour-specific bioartificial extracellular matrices to grow both cell line and patient-derived OS organoids in advanced 3D culture systems. We will chemically functionalise commercially available tumour extracts to facilitate covalent polymerisation of tumour-derived extracellular matrix molecules via photocrosslinking to create cytocompatible hydrogels with tuneable physicochemical properties.

The novel tumour representative biomaterials will allow to recapitulate OS tumours and their local environment in unprecedented detail and facilitate personalised oncology workflows with high predictive value.

Project objective

The objective of this project is to develop covalently crosslinkable bioartificial extracellular matrices (ECMs) to support OS cell line and organoid growth in vitro. This project will work closely with biotechnology company, Gelomics Pty Ltd to develop these novel biomaterials.

In this project you will:

• develop and characterise novel bioartificial ECM-based biomaterials using chemical derivatisation of tumour extracts
• assess the bioartificial ECM physicochemical parameters for cytocompatibility and mechanical properties
• determine cellular viability, proliferation, metabolic activity, and drug responses of OS cell lines and patient-derived cells in 3D cultures in the bioartificial ECM system.

Research activities

Research activities include:

• hydrogel biomaterial synthesis and characterisation
• physicochemical parameter assessment of ECM hydrogels
• 3D cell and organoid culture techniques (primary cells and cell lines)
• cell culture and cell-based assays, immunofluorescence, image analysis.

Outcomes

Bioartificial extracellular matrices that enables efficient patient-derived organoid generation, culture, treatment, and drug response analysis will be created and validated using novel chemical modification techniques applied to biological materials.

Skills and experience

Ideal candidates should:

• have previous PC2 laboratory experience
• have previous experience with cell culture and common bioassays
• be interested in tumour biology and biomaterials development
• have excellent verbal and written communication skills
• be self-motivated, able to plan and prioritise workloads to meet deadlines
• be able to take initiative and undertake complex problem-solving activities
• be ableble to work in a multidisciplinary team environment.

Keywords

• osteosarcoma
• bioengineered tumour microenvironments
• biomaterials
• 3D culture models
• drug testing
• hydrogels

Contact

Contact Dr Jacqui McGovern for more information.