PROJECTS

PROJECT #1

Deep Neural Networks for Omni-modality MSK Image Analysis

AIM

This project aims to produce, evaluate and disseminate new deep neural networks-based algorithms for the analysis of MSK images through:

To improve diagnosis, treatment planning and management of MSK patients. This will increase our understanding of the MSK disease and develop better treatment options.
To disseminate our algorithms and tools to the MSK community. This will allow other investigators from USyd, Australia and overseas, to collaborate and benefit from the project, as well as to use the preliminary validation results for further funding opportunities.
Providing training for the HDR students at the partnerâ€™s institution (hospital) to collaboratively work on algorithm design, evaluation, and implementation.

GOALS

Curating a MSK image dataset with functional, anatomical, pathological and outcome data. This will be used to build our algorithms.
Developing algorithms for the automatic segmentation of anatomical defect.
Developing algorithms for the prognosis analysis of anatomical defect e.g., early identification of patients who may develop metastatic diseases.
To establish a research lab at the partner hospital to provide training at the coalface of a clinical Department.

PROJECT #2

Advanced 3D Visualization of MSK Imaging

AIM

This project aims to innovate in:

3D visualization algorithms/techniques that enable improved diagnosis and for use in multi-disciplinary team meetings. This will allow clinicians to view the anatomical characteristics of the MSK defect without the noise and obstruction inherent in the medical images and with minimum user inputs.
To develop novel visualisation display technologies, such as with Holograms, to aid in image interpretation
Providing training for the HDR students at the partnerâ€™s institution (hospital) to collaboratively work on algorithm design, evaluation and implementation.

We anticipate that the development of new effective 3D MSK visualization algorithms/techniques will aid the clinicians and surgeons in improving the diagnosis of MSK defects and making pre-surgical planning. The developed 3D visualization algorithms/techniques will be shared with the computer graphics and medical communities. Ultimately, the medical visualization software/system with the developed 3D visualizations will be delivered to medical professionals. This will allow other investigators from the university and medicine sector to collaborate and benefit from the project, as well as to use the clinical validation results for future funding opportunities.

GOALS

To automate deep learning-based segmentation approach for the identification and derivation of the defects and the anatomical structures that can be fed into the 3D visualization pipeline (from Project 1 – Deep neural networks for omni-modality MSK image analysis).
Optimize the 3D visualization of the defects and the anatomical structures by automatically exploring the parameter space and specifying the ideal visualization parameters for both multi-modality images that ensure the visibility of the defects and surrounding structures.
Develop Interactive real-time 3D visualization by leveraging the deep learning techniques and GPU-based computer graphics, which optimizes the visibility of the defects and surrounding structures based on user selection and preferences.
To establish a research lab at the partner hospital to provide training at the coal-face of a clinical Department.

PROJECT #3

Bioactive Ceramic Coatings with Antimicrobial Properties to Increase Orthopaedic Implant Longevity

OUTCOMES

We will develop a family of ceramic coatings for orthopaedic implants, featuring osteogenic and antimicrobial properties coupled with high bonding strength to prevent premature implant failure (addressing RT2). This will reduce the costs associated with revision surgery and greatly improve the recipientsâ€™ long-term quality of life. Biosensors can be incorporated to facilitate monitoring and stimulation of the tissue regeneration (Project 7). Training: Two ICHDRs will develop extensive skills in biomaterials processing and characterization techniques, to develop new ceramic coatings with antimicrobial properties (addressing TT1). Osseointegration, Allegra, and Peter Brehm will provide industry direction and associated training for the development, design, production, and commercialization of medical implants (addressing TT2). Methods: The short lifespan of orthopaedic implants is a major clinical problem, where failure often occurs within a few months as a result of infection, or within 10â€“15 years due to loosening. Most orthopaedic implants use titanium alloys (Ti-6Al-4V), which often cannot achieve sufficient integration with bone, and currently used hydroxyapatite coatings are prone to delamination and fragmentation. This project will develop our family of patented ceramics for use as novel implant coatings: Baghdadite (US patent 9,005,647), Sr-HT (US patent 8,765,163), and Sr-HT-Gahnite (US patent 9,220,806). We will optimize the plasma-spraying process for coating deposition to produce high bonding strength while ensuring that the inherent bioactivity and antimicrobial properties of the ceramics are retained.

PROJECT #4

Quick-release, Fail-safe Connector between Osseointegration Implants and Artificial Limbs

OUTCOMES

We will develop a connector to couple osseointegration implants to artificial limbs (addressing RT2). This device will enhance the functionality and safety of osseointegration implants and will assist in promoting their widespread use as an emerging technology to improve the treatment of lower limb amputees. This project will draw on image analysis (Project 1), scaffold construction (Project 3), and computational modelling (Project 9). Training: One ICHDR will receive training in medical device development, including design, computational modelling, materials selection, device manufacturing and testing, and regulatory knowledge, to produce a safe, viable, and economical device that meets market demands (addressing TT1). Osseointegration will provide specific design inputs, materials of the current devices, regulatory expertise, and direct access to patient feedback, as well as facilitate the manufacturing of prototypes (addressing TT2). Methods: Osseointegration implants have been developed over the past two decades as a new technology for mobilizing patients with lower-limb amputations, offering many benefits over traditional socket prostheses, including improved function and quality of life. Currently, artificial limbs for osseointegration implants are connected through traditional mechanisms used in the socket prosthesis system based on rigid screws and bolts that limit the versatility of the implant. As osseointegration implants become more common, there is a pressing demand for an ideal connector system designed specifically to meet the requirements of individual patients. Our goal is to develop a unique and cost-effective connector system between osseointegration implant and artificial limb to allow: (1) quick and easy release for the recipient to rapidly attach and remove the artificial limb as required, and (2) a fail-safe mechanism to prevent undesirable impact and strain passing through the implant site, and to protect residual bone from breakage in the event of a fall.

PROJECT #5

Implantable Biosensors to Monitor and Stimulate Tissue Regeneration

AIM

The project will develop a comprehensive active sensor and stimulation system â€“ an instrumented MSK implant that measures a range of physical, chemical, and physiological conditions to monitor rehabilitation and implant failure (addressing RT3). Implant placement can be guided by imaging (Projects 1 and 2). Sensor information will become inputs for computational modelling (Project 9).

GOALS

Deploy integrated sensors and stimulators within osseointegrated implants to monitor and promote the healing process for improved integration, health management
Enable long-term data acquisition capabilities, to assist in directing future research and innovation based on a major advance in the knowledge base.

PROJECT #6

Smart Dressings to Diagnose, Stimulate and Monitor Musculoskeletal Tissue

AIM

This project will develop new silver nanowire dressings for interfacing to a miniaturised bioimpedance measurement system. The wearable system will be used to measure tissue properties (RT3) from locations identified by imaging scans (Project 1 and 2).

GOALS

The goal of project 8 is to develop smart dressings that provide diagnostic and monitoring data of MSK tissue and investigate the capacity of smart dressings to stimulate to promote osseointegration. Besides the main goal, project 8 also looks at studies on disability rehabilitation with exoskeleton and computer vision for monitoring and assessing the efficacy of rehabilitation therapy.

PROJECT #7

Developing the Next Generation of Fluorescent Nanoparticles for Biosensing and Bioimaging

AIM

In the last few years, fluorescence spectroscopy has emerged as a highly attractive analytical technique to rapidly and sensitively detect and monitor biomolecules in cells and bodily fluids. Over the past two decades, a wide variety of fluorescent sensory materials have been synthesized, such as fluorescent proteins, graphene sheets, and semiconductor quantum dots. While each of these materials have their advantages, they collectively suffer limitations from high noise-to-background fluorescence ratios, large particle sizes, synthesis complexity, low photostability, poor resolution, and toxicity. We aim to overcome these limitations by developing the next generation of carbon-based fluorescent nanoparticles, Carbon Dots (CDs), with combinational properties of monodispersity, high photostability, biocompatibility, low cytotoxicity, good cell permeability, high resolution two-photon deep tissue imaging. We plan to use the novel CDs for developing a real-time quantitative probe for targeted in vivo monitoring the osteoclast activity and bone substitute resorptive activity (these activities can cause severe exctra- and intra-cellular pH dysregulation).

GOALS

To synthesis novel CDs with a narrow size distribution, which is essential for fine-tuning their electronic and optical properties, biocompatibility, and cellular interactions.
To perform comprehensive optimization of the synthesis and post-synthesis parameters employed for the synthesis of CDs to gain a better understanding of the effect of these parameters on photophysical and biological properties.
To synthesis and characterize novel pH-sensitive fluorophores using organic synthesis.
To engineer and design the surface of CDs with ultra pH-sensitive fluorophores (synthesized in step 3) and bone targeting moieties through a novel conjugation method to develop a novel pH-sensitive two-photon ratiometric CDs-based probe.

To investigate the capability of the developed probe for targeted in vitro and in vivo monitoring of the osteoclast function after bone graft implantation.

PROJECT #8

To Develop a Multifunctional Biomaterial for Bone Regeneration

AIM

Globally, bone- and joint-related degenerative problems are a major cause in 50% of all chronic diseases in people over 50 and cause debilitating pain and loss of independence. 3.8 million bone-grafting procedures globally are performed each year, to repair non-union and osteoporoticÂ fractures; the demand for orthopaedic implants is ever-increasing due to increasing levels of obesity, population ageing, and growth in sports-related injuries. Current treatments using autografts or allografts for bone regeneration have serious limitations, triggering the growing demand for synthetic bone substitutes; and a major orthopaedic challenge with insufficient osseointegration for the implant with surrounding bone tissue. We aim to overcome these limitations by developing a bone biomaterial with combinational functions: including strong mechanics, excellent bone biocompatibility, anti-ageing, or antimicrobial.

GOALS

1) To develop a ceramic scaffold possessing novel architecture, chemical, and mechanical properties that provide strong mechanical property, excellent bioactivity, particularly having anti-ageing function for large bone defect regeneration application. 2) To develop an implant coating strategy with a novel ceramic possessing structural and chemical, and mechanical properties that provide an anti-ageing and antimicrobial environment, thereby overcoming premature implant failure and improving osseointegration.

PROJECT #9

Flow Lithographic Fabrication of a Structured Bone Microtissue

RATIONALE

Tissue engineering and stem cells have the potential to regenerate bone damaged by trauma or disease. First, however, it is necessary to address the challenge of fabricating synthetic scaffold structures that can support true tissue function. While pluripotent-stem-cell-derived tissue-models have been established with increasingly physiological shape, size and function1,2, the histo-and-morphogenetic processes present in these models proceeds stochastically. This reflects an absence of technologies able to produce complex supportive cell niches that can reproducibly guide tissue patterning and generate well-defined tissue structures. Scaffold materials require a heterogeneity rivalling that of native tissue; this includes supporting multiple cell lineages through a complex structured architecture rich with multiphasic inductive interactions specifically directed to bone, muscle, tendon or cartilage regeneration. However, while current approaches to fabricating such structured material systems have demonstrated the spatial patterning of bioactive molecules and peptides, there has been limited success in fabricating materials that support structured multilineage cell culture able to recapitulate tissue function.

AIM

To fabricate a complex bone microtissue in which spatially defined biophysicochemical cues regulate pluripotent stem cell differentiation to recapitulate the tissue-scale heterogeneous structure and the cellular composition of bone marrow.

PROJECT #10

Novel Biomaterials, Surface Coatings and Antimicrobial Devices

GOALS

Development of novel ceramic materials for musculoskeletal applications
Novel 3D-printed patient specific implants
Bioactive ceramic coatings with antimicrobial properties to increase orthopaedic implant longevity

PROJECT #11

Electroceuticals for Musculoskeletal Applications

GOALS

Implantable sensors and stimulation for robotic prosthetics
Printable stick-on sensors for muscle and wound healing monitoring and stimulation
Brain computer interfaces for prosthetic control
Optimise patient health and surgical outcomes

PROJECT #12

Nano Particles for TheranosticsÂ

AIM

Multifunctional theranostics magnetic and fluorescent nanoparticles for diagnosis and treatment of diseases

PROJECT #12

Nano Particles for TheranosticsÂ

AIM

Novel 3D printing technology to generate organoid systems

Tel: 0061 2 9114 4607
Email: [email protected]

@2021 ARC Centre for Innovative BioEngineering

Level 4, J07
Faculty of Mechanical Engineering
University of Sydney
Darlington NSW 2008
Australia