Biomechanics, biomaterials, cell therapy and tissue engineering

The worldwide shortage of donor organs and drawbacks of surgical methods have created significant challenges in repairing and replacing diseased or damaged tissues and organs. This pressing need has led to the rise of ‘tissue engineering and regenerative medicine’, a multidisclinary field which aims to induce the body’s natural regenerative abilities and produce functional substitutes of biological tissue for clinical use.

The fundamental concept combines various tissue engineering elements, most often a scaffold as a supporting matrix in combination with living cells and/or bioactive molecules, to form a tissue engineering construct that repairs or regenerates the diseased or damaged tissue or organ.

Advances in medical technology have contributed to the world’s ageing population and increased life expectancies. Unfortunately, this has also caused a drastic increase in musculoskeletal conditions impacting bones, joints and tendons, which impose annual costs of $5.7 billion on the Australian healthcare system. The demand for bone graft substitutes is estimated to increase by 30 percent from 2013 to 2020.

Tissue engineering and regenerative medicine can provide a novel treatment regime based on the use of synthetic biomaterials, which may be constructed into three-dimensional implants and combined with biologics (such as cells and/or bioactive molecules). This will positively impact the quality of life of millions of people who are affected by musculoskeletal conditions globally.

Our experts: Professor Hala Zreiqat, Dr Yogambha Ramaswamy

Immunotherapy is an alternative and complementary treatment for cancer patients that lowers the risk of cancer reoccurrence. Immunotherapy involves harnessing the body’s immune system or T cells to combat the disease by directly killing the infected cells.

We aim to gain a better understanding of the relationship between T cell functions and their physical microenvironment by 3D printing hydrogels as a model for the soft tissues and organs in our bodies. Increased knowledge of how T cells function will lead to improved cancer therapies and immunotherapies.

Our experts: Professor Hala Zreiqat, Dr Gurvinder Singh

We aim to establish novel synthetic routes to fabricate hybrid or composite multifunctional nanobiomaterials across different length scale from plasmonic, magnetic, polymeric and biomolecules. Physical properties of hybrid materials can be tailored by varying the size, shape and composition of nanomaterials.

The techniques for surface engineering will be established to add multifunctionality (biocompatibility, targeting agent and drug loading) that will allow the design of next-generation multifunctional nanomaterials. Applications of research outcomes will have significant impact on the field of advanced nanobiomaterials for tissue engineering, target drug delivery, imaging contrast for MRI and CT scan and therapy.

Our experts: Professor Hala Zreiqat, Dr Mohammad Mirkhalaf, Dr Peter Newman  

Until now, current biofabrication technologies have been unable to recapitulate the complex properties of tissue. Tissue exhibits unique mechanical, biochemical and structural properties, with discrete and continuous changes in cellular and extracellular composition that defines intricate channels, chambers and interfaces. Recreating these intricate systems necessitates technologies able to fabricate materials with mechanical, biochemical and structural heterogeneity with microscale precision.

We're developing 3D printing technologies for fabricating materials with defined microscale properties. Our new approach is capable of fabricating materials with discrete changes, gradients or otherwise arbitrary mechanical and biochemical material properties across the physiologically relevant range. Using printed material of varying heterogeneous cues, we are fabricating structured bone microtissues.

Our experts: Professor Hala Zreiqat, Dr Mohammad Mirkhalaf, Dr Peter Newman

Bone, seashells and fish fins are biological materials that display features of unique combinations of toughness and strength, as well as bioactivity and shape morphing. In materials science and engineering, the development of these novel materials with similar complex combinations of properties and functionalities is a major challenge.

Our research aims to identify the main structural features of these biological materials and their associated deformation mechanisms, and implement these in bioceramics that will interact with biological systems, other engineering materials such as glasses, ceramics and composites.

Our experts: Professor Hala Zreiqat, Dr Young No

Australia has one of the highest rates of tendon and ligament rupture in the world. The process of repairing ruptures usually involves additional surgery which has a high risk of disease transmission due to the introduction of tendons from another part of the body or donor. Previous attempts to develop synthetic materials for tendon and ligament repair have been unsuccessful due to poor biomechanics and biological properties.

Our strategy is to engineer synthetic fibre-reinforced hydrogels from biocompatible materials with superior tensile strength and water content that mimics the native tendons and ligaments, and further incorporates synthetic bioactive materials and biomolecules to enhance the regeneration of tendon and ligament tissues.

We're also developing strategies to enhance the integration of the synthetic scaffold at the bone and muscle interface to eliminate the risk of re-rupture, often associated with tendon and ligament repair.

Our experts: Professor Hala Zreiqat, Dr Mohammad Mirkhalaf, Dr Young No

Osteoarthritis is a painful disease where parts of the articular cartilage responsible for the smooth movement of the joints has been degraded, leaving the bones to rub against each other. Cartilage tissue has poor healing capacities due to its low cell content and low blood supply.

We aim to develop tough, biodegradable and bioactive hydrogels to replace and repair articular cartilage by engineering hydrogel-ceramic composites. The hydrogel component is made of a biodegradable material that essentially does not break under compression, along with a high-water content and porosity that mimics native cartilage. The ceramic component will release trace metallic ions that have been shown to enhance the regeneration of cartilage tissues.

Our experts: Professor Hala Zreiqat, Dr Young No

Meniscus tears affect almost 15,000 Australians annually and is the most common form of knee joint injury, presenting pain and discomfort for the patient. The meniscus plays and important role for joint stability, lubrication and force transmission in the knee joint. Following injury, if left untreated, or after partial or total removal of the damaged meniscus is carried out, a patient has increased risk of developing osteoarthritis or degeneration of the articular cartilage in the future.

We're developing custom-shaped implantable synthetic meniscus scaffolds using a combination of medical imaging, computer-aided 3D design, and biomaterials engineering strategies.

Our experts: Professor Hala Zreiqat, Dr Young No

Calcium phosphate cements (CPC) have been used to fill irregular-shaped bone defects caused by disease or trauma. To support the mechanical loading and structural integrity of irregular bone defects caused by disease or trauma, calcium phosphate cements (CPC) have been used during the healing process. Brushite cement, a special type of CPC, has been shown to degrade inside the bone and support surrounding bone tissue growth. However, there are concerns about the acidity of brushite cements and substantial heat generation during its cement reaction. The mineral composition is similar human bone and is often difficult to distinguish between brushite cements and the surrounding bone under conventional x-ray imaging.

To address these issues, our project aims to develop brushite cements modified with novel bioactive ceramics. Our research focuses on bioactive ceramics doped with denser elements such as zirconium and strontium capable of both reducing the acidity and enhancing the x-ray visibility.

Our experts: Professor Hala Zreiqat, Dr Mohammad Mirkhalaf, Dr Young No

Worldwide, there are more than two million bone grafting surgical procedures to treat fractured bones arising from trauma, often exacerbated by underlying diseases such as osteoporosis. With additional surgery and the increased risk of disease transmission, bone grafts from a patient’s own body or from a donor can be used. 

We're developing novel ceramic materials that support the growth and regeneration of bone tissue with high strength, high toughness and high x-ray visibility properties.

Our experts: Professor Hala Zreiqat, Dr ZuFu Lu,

Metal ions and biomolecules play key roles in many biological processes, and their anomalous homeostasis in cells is related to diseases such as neurological disorders, cancer and diabetes.

Fluorescence imaging offers a unique route to detect the amount and location of metal ions and biomolecules in cells in a non-invasive way and allows us to better understand the physiological and pathological functions of metal ions and biomolecules in cell biology.

The project involves a synthesis process of a Carbon Quantum Dots (CQDs). The synthesised CQDs are designed and conjugated to achieve an optimised probe with biosensing and bioimaging applications.

Our experts: Professor Hala Zreiqat

Injuries and joint damage associated with young adulthood from playing sport can evolve into chronic injuries if treated incorrectly, leading to musculoskeletal diseases later in life.

Current therapies only deliver short-term improvements with many people suffering years of discomfort and pain from an injury that failed to heal satisfactorily. Such chronic joint injury can cause progressive and irreversible damage, ultimately resulting in osteoarthritis. This condition, which affects 1.8 million Australians and 15% of the world’s population, is extremely debilitating and painful.

Our research aims to develop an entirely new treatment for joint injuries by combining cell therapy with synthetic biomaterials to help maximise joint repair and reduce the likelihood of the injury developing into osteoarthritis.

Our experts: Professor Hala Zreiqat, Dr Ali Entezari

Ligament reconstructive procedures are common practice following ligament rupture and instability. Vital to the success of ligament reconstruction is adequate graft fixation without infection or rejection – a feat not widely achieved by current metallic solutions.

In collaboration with our industry partner, Allegra Orthopaedics Ltd, we are developing interference screws from a novel biodegradable ceramic material using innovative 3D printing techniques to overcome issues associated with current metallic fixators. The securing of ligament grafts with this bioceramic material will provide the strength required for initial fixation to the bone, with subsequent degradation and eventual replacement with the body’s own bone.

Our experts: Professor Hala Zreiqat

Skeletal fracture is a leading contributor to personal and socioeconomic burden. Although most fractures heal well, complications commonly arise in bones that are resistant to treatment and subject to delayed healing or nonunion. The search for a biomaterial that can successfully replace autografting has led to the emergence of synthetic bone void fillers.

However, to date, synthetic biomaterials have failed to simultaneously achieve the strength and toughness for load-bearing applications; implant architecture and bioactivity for osteoconductivity; and biodegradation to leave the body free of permanent materials. There remains a gap in the literature for an preformed, malleable, bone void filler material suitable for use in osseous defects of structurally integral bones. 

By investigating the effects of polymer and ceramic properties including material, size, and shape; this project aims to develop a composite bone void filler strip with properties optimized for load-bearing use. 

Our experts: Associate Professor Colin Dunstan, Professor Markus Seibel, Professor Hong Zhou

Bone tissue provides a fertile environment for cancer cells leading to the preferential metastasis of many cancers to bone including in particular breast cancer and prostate cancer. It is becoming apparent that bone tissue provides a receptive niche for cancer targeting to bone. The nature of the cell-to-cell interactions leading to targeting to bone of cancer cells is very important for full understanding and prevention of cancer metastasis to bone.

In particular this research has identified a role for vitamin D signalling directly on cancer cells and for changing the secretome of mesenchymal stem cells found in bone to promote cancer cell proliferation and the ongoing aim of this project is to identify the important components of the activated signalling pathways.

Our experts: Associate Professor Colin Dunstan,Professor Michael Murray

Our collaborators: Dr Tristan Rawling (UTS)

Treatment of breast cancer cells with analogues of omega three fatty acids is associated with either suppressed cell proliferation or reduced ability of breast cancer cells to migrate and to invade their way through matrix – a predictor of metastatic potential. Some analogues are able to potently inhibit tumour growth in vivo.  Ongoing research is evaluating the effects of chemical modulation of these analogues and determining their mechanisms of action on breast cancer.

Our experts: Professor Hala Zreiqat, Dr ZuFu Lu

Reprogramming fibroblasts into induced pluripotent stem cells (iPSCs) is an effective route for tissue repair an regeneration as iPSCs represent a potentially unlimited cell source for tissue applications and allows patients to use their own cells for tissue repair and regeneration without immune rejection. Whilst a successful, the approach is compromised due to the complexity of iPSCs production involving using genetic approach as well as the risk of teratoma formation resulted from the residual iPSCs.

In order to address the limitations of using iPSCs, we are developing new chemically-defined reprogramming technology to directly convert fibroblasts into osteoblasts without passing through the pluripotent state as a promising cell source for bone tissue repair or regeneration.

Our experts: Professor Hala Zreiqat, Dr ZuFu Lu

As we age, the onset and progression of degenerative bone diseases is caused by a cellular sensescence, a form of stable cell cycle arrest induced by cellular stress, and the proportion of senescent cells in our body increases. Behaving differently to regular cells, senescent cells and are characterised by senescence associated secretory phenotype (SASP) which creates a chronic inflammatory microenvironment detrimental for tissue repair and regeneration. With elderly patients, tissue-engineered approaches to treat diseases may need to be tailored and focus on these senescent cells.

We aim to gain more insight into the roles of how senescent stem cells and osteoblasts contribute to bone tissue repair and regeneration, and develop novel strategies focusing on these senescent cells and creating such a pro-regenerated microenvironment for tissue repair and regeneration.