Pathophysiology And Prevention Of Methotrexate Chemotherapy-induced Bone Growth Defects
Funder
National Health and Medical Research Council
Funding Amount
$622,598.00
Summary
Childhood chemotherapy often causes growth arrest, osteoporosis, and fractures in cancer patients and survivors. Using a rat model, this project will study how the most commonly used chemotherapy drug methotrexate causes bone growth defects and examine any protective effects of two natural-derived substances. This work will increase our knowledge on chemotherapy-induced bone growth defects, and will be useful for developing a preventative treatment.
Mobilisation Of Endogenous Mesenchymal Progenitor Cells For Growth Plate Regeneration
Funder
National Health and Medical Research Council
Funding Amount
$605,251.00
Summary
Growth plate cartilage is responsible for bone growth in children. Its injury is common and is often repaired undesirably by bony tissue which causes significant bone growth defects. This project will develop a biological treatment through mobilising endogenous progenitor cells to enhance growth plate regeneration and prevent bone growth defects, which will allow patients to avoid highly invasive/costly corrective surgeries.
Roles Of Injury-induced Inflammatory Response In Regulating Bony Repair At Injured Growth Plate Cartilage
Funder
National Health and Medical Research Council
Funding Amount
$366,301.00
Summary
Children's growth plate cartilage is responsible for bone lengthening. Due to popularity of sports and play, trauma-induced growth plate damage and subsequently bone growth defects are common in children, with up to 30% of growth plate injury cases resulting in growth abnormality, for which the present surgical correction is highly invasive and not fully effective. Although we know that the growth plate injury-induced bone growth defects result from bony repair of the injured growth cartilage, w ....Children's growth plate cartilage is responsible for bone lengthening. Due to popularity of sports and play, trauma-induced growth plate damage and subsequently bone growth defects are common in children, with up to 30% of growth plate injury cases resulting in growth abnormality, for which the present surgical correction is highly invasive and not fully effective. Although we know that the growth plate injury-induced bone growth defects result from bony repair of the injured growth cartilage, we largely don't understand why and how this bony repair occurs. Understanding mechanisms for this faulty bony repair of injured growth plate will be critical prior to effective biological treatments can be developed. Recently, using an injury model in young rats, we found that bony tissue formation at injured growth plate is preceded sequentially by inflammatory, fibrogenic, chondrogenic and osteogenic responses. The inflammatory response is an initial event and our recent studies suggest that inflammatory response recruits inflammatory cells and produces important molecules that could significantly influence subsequent fibrogenic, chondrogenic and osteogenic events leading to the bony repair of the injured growth plate cartilage. The current proposal further addresses roles of the inflammatory response and the molecular pathways of this response in regulating downstream bony repair events. This project will generate novel understanding on the faulty bony repair of injured growth plate, and will provide valuable information for developing cost-effective and simple therapeutic intervention that aims to prevent bony repair and to enhance cartilage regeneration of the injured growth plate in children.Read moreRead less
Engineering The Second Generation Of Growth Factors And Cytokines For Regenerative Medicine Applications
Funder
National Health and Medical Research Council
Funding Amount
$538,848.00
Summary
Growth factors and cytokines have a great potential for regenerative medicine applications. Yet, most of these molecules have failed to show efficacy in humans or raised major safety concerns, due to high dosing and inappropriate delivery systems. In this project, we seek to engineer the next generation of growth factors and cytokines to display much better effectiveness at low doses. We will directly impact applications for chronic wounds, skin scar prevention, and bone regeneration.
Optimising Bone Regeneration Using Advanced Design And Fabrication Technologies
Funder
National Health and Medical Research Council
Funding Amount
$916,671.00
Summary
The aging population has produced a rapidly increasing demand for synthetic implants that can regenerate lost or diseased bone. This project will produce an implant that represents a viable alternative to bone autografts and allografts with broad applications for the repair of large or challenging bone defects. Such an achievement will have significant healthcare benefits by reducing patient morbidity and recovery time, and improving long-term outcomes.
I am an orthopaedic surgeon and clinician-scientist based at Sydney’s largest children’s hospital. My goal is to improve treatments for children with traumatic injuries and bone deformity. I have worked in bone research for over 20 years. My current research interests are finding new treatments for drug-resistant bacterial infections, treating genetic bone disease, and developing new medical devices to help children’s bones grow straight.
Tyrosine Kinase Receptor C-ros-oncogene 1 Mediates Twist-1 Haploinsufficiency Induced Craniosynostosis In Children: A Novel Therapeutic Target
Funder
National Health and Medical Research Council
Funding Amount
$562,863.00
Summary
Children with Saethre-Chotzen syndrome exhibit premature fussed coronal sutures, and other skull/ skeletal malformations. Surgical intervention is the only treatment option to ensure optimal cognitive and skeletal development. Our studies have identified a candidate molecular pathway that regulates bone formation by cranial bone cells from these patients. Targeting these key molecular signalling components with chemical inhibitors will help prevent the premature fusion of cranial sutures.
Bioactive And Biodegradable Scaffold And Novel Graft Source For The Repair Of Large Segmental Bone Defects
Funder
National Health and Medical Research Council
Funding Amount
$451,103.00
Summary
The treatment of large bone defects arising from trauma and tumour remains a challenge to orthopaedic surgeons. This project combines a well-established scaffold that can be custom-made to address patient specific requirements with a novel source of graft that can be harvested in significant volumes with minimal pain and morbidity. This novel tissue engineering approach will be evaluated in a previously established pre-clinical model that reflects the severity of challenging clinical scenarios.
Pre-clinical Validation Of A Novel Implant For Bone Tissue Engineering
Funder
National Health and Medical Research Council
Funding Amount
$435,767.00
Summary
The aim of this grant to was examine a new method for manufacturing implants to improve repair of critical bone defects. It involves new technology for the manufacture of porous scaffolds and testing their delivery in a biological, bone repair setting.
Novel Strategy For The Treatment Of Large Bone Defects Using A Unique Biomaterial With Tailored Microstructure
Funder
National Health and Medical Research Council
Funding Amount
$314,644.00
Summary
There is a rapidly increasing and pressing medical need for the development of synthetic implants that can regenerate large amounts of lost or diseased bone. This project will produce a unique implant with optimal mechanical and biological performance, which represents a viable alternative to bone grafting with broad applications for the repair of large or challenging bone defects. Such an achievement will produce significant healthcare benefits and improved long-term outcomes.