Wound Healing Efficacy of Therapeutic Extracellular Vesicles Generated by a Two-Photon Printed Nanodevice

About this project 

Extracellular vesicles (EVs) are key indicators and mediators for various cellular processes. Studying EVs for fundamental biology or applying EVs for biological applications requires efficient isolation from their cellular environments. This project aims to utilise state-of-the-art two-photon polymerisation (TPP) 3D printing technology to develop microfluidic tools for harvesting EVs from live cells and investigate their biological properties for therapeutic applications. 

Common EV isolation techniques include size-based (e.g., filtration and chromatography), density-based (e.g., centrifugation) and affinity capture-based methods, which are often time-consuming or involve complex handing steps. To achieve required EV yield and purity, a combination of methods is frequently employed. Moreover, microfluidic systems have been integrated with some of the approaches (e.g., size-exclusive and affinity-based methods) to streamlining the isolation process and improve efficiency. However, there are challenges in microfluidic EV separation, including complex device fabrication and optimisation, reproducibility and robustness of the isolation results, and the device’s adaptability to different biological samples. 

The project proposes to leverage the TPP 3D printing capability at ANFF-SA to fabricate smart micro/nanostructure, such as nanomembrane, within a 3D printed fluidic device for the separation of EVs from live cells. The micro/nanostructure will be designed to support live cell culture within the device and enable cell-derived EVs pass through to be collected downstream for characterisation and analysis. The project is anticipated to enhance the study of EVs, particularly those derived from stem cells, for therapeutic applications. The development of a highly integrated fluidic device with the dual capability to sustain cell cultures and separate EVs will offer broader potential for EV research in various biological contexts.
UniSA’s Future Industries Institute (FII) is home to world class facilities and expertise in wound healing and micro/nanofabrication, spin out companies in biomaterials (Tekcyte) and cell therapy (Carina Biotech), and delivered research in the Cell Therapy Manufacturing CRC. Fertilis – a biomedical device manufacturer - is currently embedded in FII to advantage from equipment unique in Australia. This project also aligns with the National Research Priorities (Priority 2: Supporting healthy and thriving communities) and the ambitions of NCRIS in supporting and translating research that has industrial and societal impact. UniSA’s PC2 tissue culture labs, including a histology suite, Fortessa flow cytometer, fluorescent and light microscopy (Microscopy Australia), and Core Animal Facility (City West) will be essential in this project. ANFF-SA’s UpNano (first in Australia) will enable nanofabrication of novel devices that demonstrate national leadership in advanced manufacturing. This project builds on a major societal need and UniSA research strength. The endemic of chronic non-healing wounds effects 1-2% of the world population, or 450,000 Australians at a health care cost of > $3B/year. However, the gold standard of care is still wound management, not treatment. We have produced an advanced dressing for treatment of chronic diabetic foot ulcers. These wounds effect 25% of the 1.7 million diabetic patients in Australia and of these 15-20% require a lower limb amputation. The survival rate after amputation is poor; > 50% after 5 y. The advanced dressing delivers stem cells into diabetic wounds to accelerate healing. The team has shown that stem cell treatment is via the release of active proteins from EVs into the wound environment thus using EVs directly maintains the therapeutic potential of stem cells without the possibility of immune rejection. This project will look to overcome existing limitations of cell therapy (immune response and manufacturing delay) to create EV therapy, based on manufacturing micro/nanofluidic devices and preclinical testing in wound models.

What you’ll do

This project will deliver three work packages: 

1. Nanofabrication of tailored on-chip membranes: TPP nanoprinting offers unparalleled precision and versatility of structural design; however, the technique is still emerging and the envisaged nanostructures will require detailed study. This includes the design and material limitations for cell cultures and biocompatibility, focusing on membranes that aid EV production or isolation. 
2. Microfluidic profiles for EV optimisation: Release of EVs will be studied to enable optimisation of production, homogeneity, and collection mechanisms. The student will compare experimental EV production and release in bulk and on the new chip platform. 
3. Efficacy in would healing: The student will study the effects of EVs on cell proliferation and migration, and blood vessel formation in cell lines (lab and preclinical). Skin equivalents models will be used to test the EVs ability to promote healing in skin, including in vivo models of diabetic healing, and compare results for EVs from conventional and microfluidic methods, testing our hypothesis that therapeutic EVs can be manufactured in novel chips for wound treatments. 

The student will publish in leading manufacturing, interfacial science, nanobiotechnology, and biomedicine journals (see supervisory team’s record). Project IP may include structural designs, fluidics, and therapeutic EV formulations. 

Engagement with Fertilis will foster investment and collaboration, building on a successful relationship. 

Where you’ll be based 

This project will be based at the Future Industries Institute, home to $20M world-class micro/nano-fabrication facilities, led by the Principal Supervisor Prof. Craig Priest, and state-of-the-art biomaterials and wound science laboratories, led by Prof. Allison Cowin. 

The student will benefit from this unique combination of facilities and expertise, which will be vital for the multidisciplinary research proposed. In particular, the Australian National Fabrication Facility's UpNano NanoOne two-photon polymerisation nano-printer is unique in Australia and ECR co-supervisor Dr Bin Guan is a leading expert. Prof. Priest and Dr Guan are close collaborators with both the local industry partner (Fertilis Pty Ltd) and the equipment manufacturer (UpNano, Austria). Industry partner Fertilis Pty Ltd co-locates company staff with the instrument on-campus, creating a vibrant academic-industry advisory environment for the PhD student in fabrication and device design. 

Dr Stuart Mills is an expert in wound biology and has conducted preliminary cell culture experiments on nanomaterials (developed by Dr Guan and Prof. Priest) that support the feasibility of this project. Financial Support  

Scholarship and project open to both Domestic and International applicants: This project is funded for reasonable research expenses. Additionally, a living allowance scholarship of $35,200 [2025 rate] per annum is available to eligible applicants. 
Australian Aboriginal and/or Torres Strait Islander applicants will be eligible to receive an increased stipend rate of $50,291 per annum. A fee-offset or waiver for the standard term of the program is also included. 
For full terms and benefits of the scholarship please refer to our scholarship information for domestic students or international students.

Eligibility and Selection 

This project is open to application from both Domestic and International applicants.
Applicants must meet the eligibility criteria for entrance into a PhD. 

Additionally applicants must meet the project selection criteria: 

• A tertiary degree, or equivalent professional accreditation and standing, in either biology, engineering, chemistry, or materials science or a closely related discipline. 
• Demonstrated technical and practical experience in a scientific laboratory setting or technical engineering capacity. 
• Ability to work effectively with colleagues in a diverse and collaborative environment, while managing competing project priorities. 
• Quality written, verbal, and interpersonal skills to effectively communicate scientific concepts and results, such as through conferences presentations, academic publications, or industry reports. 
• Proven ability to work effectively and cooperatively with staff and students from diverse backgrounds, displaying initiative and commitment.

All applications that meet the eligibility and selection criteria will be considered for this project. A merit selection process will be used to determine the successful candidate.

The successful applicant is expected to study full-time, and to be based at our Mawson Lakes Campus in the north of Adelaide. The student may be required to travel between campuses or to conferences and events. Note that international students on a student visa will need to study full-time.

Essential Dates 

Applicants are expected to start in a timely fashion upon receipt of an offer. Extended deferral periods are not available. Applications close on 18 December 2024.