Heat Shock Transcription Factors In Bone Remodeling And Disease
Funder
National Health and Medical Research Council
Funding Amount
$480,427.00
Summary
The denisity of bone is finely balaned and required for a healthy lifestyle. During times of disease, damage or drug treatments the bone can be compromised, often decreasing in density and becoming fragile. This often leads to fractures, pain and a poor quality of life. This proposal seeks to investigate whether stress insults to bones plays a role in the loss of bone. This will provide new insights into bone loss during disease and lead to novel treatment strategies.
Biological, Functional And Radiographic Evaluation Of Autologous Chondrocyte Implantation
Funder
National Health and Medical Research Council
Funding Amount
$307,400.00
Summary
We will test the hypothesis that autologous chondrocyte implantation (ACI) and extensor realignment produces superior clinical, biological and radiographic results when compared with conventional treatment of realignment and debridement. We will specifically address the following aims: 1. Quantify the clinical outcome of ACI compared to the traditionally used treatment of debridement through the use of functional evaluation in a blinded randomised controlled clinical trial; 2. Evaluate the radio ....We will test the hypothesis that autologous chondrocyte implantation (ACI) and extensor realignment produces superior clinical, biological and radiographic results when compared with conventional treatment of realignment and debridement. We will specifically address the following aims: 1. Quantify the clinical outcome of ACI compared to the traditionally used treatment of debridement through the use of functional evaluation in a blinded randomised controlled clinical trial; 2. Evaluate the radiographic changes in the patellofemoral joint that occur as a result of ACI, using high resolution magnetic resonance imaging (MRI) to quantify the regeneration of hyaline articular cartilage; 3. Using the new technique of confocal arthroscopy, we will compare the histologic appearances of the ACI graft and its interface with adjacent articular cartilage; 4. Evaluate patient, surgical and explant chondrocyte characteristics in relation to functional, radiographic and biological outcomes. With respect to the matrix-induced autologous chondrocyte implantation (MACI) technique, we wish to clarify the clinical practice as a definitive treatment for articular cartilage defects. This will be the first randomised, controlled clinical trial of the MACI technique compared to that used by other groups. A positive clinical outcome from this trial will help promote the three cornerstones of this procedure – successful cell culture, efficient surgical procedures, and complimentary postoperative rehabilitation. Furthermore, this research will: a) Enhance the expansion of the MACI technique; b) Encourage development of endoscopic techniques of implantation using a combination of – • Preoperative defect registration with MRI • pre-cut custom patches, implanted with • Computer-assisted navigation techniques: c) Increase the potential to cater for a larger number of patients requiring articular cartilage repair; d) Confirm the long-term durability of regenerated cartilage in the 4th year and beyond; e) Add further commercial value by demonstrating MACI may prevent the onset of osteoarthritis.Read moreRead less
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