GENERATION OF VASCULARISED, BIOENGINEERED SOFT TISSUES
Funder
National Health and Medical Research Council
Funding Amount
$445,045.00
Summary
One of the most exciting areas in reconstructive surgery today is the tissue engineering of body parts, the process by which blood vessels are implanted into skin, muscle, bone, cartilage or even synthetic materials, to build composite living structures. Once a circulation becomes established, the engineered part can be transferred by joining the implanted blood vessels to corresponding ones at the recipient site. We have discovered that new tissue will grow out of a surgically created blood ves ....One of the most exciting areas in reconstructive surgery today is the tissue engineering of body parts, the process by which blood vessels are implanted into skin, muscle, bone, cartilage or even synthetic materials, to build composite living structures. Once a circulation becomes established, the engineered part can be transferred by joining the implanted blood vessels to corresponding ones at the recipient site. We have discovered that new tissue will grow out of a surgically created blood vessel loop placed in a cylindrical plastic chamber filled with a scaffold made of naturally occurring structural molecules. In Part 1 of this project, it is planned to optimise the rate of new vascularised tissue growth through the addition to the growth chamber of various biodegradable scaffolds. In Part 2, we aim to produce fat by 3 possible methods using: (a) cells from the rat scrotum, (b) skeletal muscle separated from its blood supply for 24 hours, or (c) bone marrow-derived stem cells, as well as bone from stem cells of the same source. In Part 3, vascularised bone, fat and connective tissue, as produced in Part 2, will be microsurgically transferred to another site in the body to study the short-term (4 weeks) and long-term (12 weeks) survival and changes (if any) in these tissues. These unique methods are currently being patented. This technology introduces the possibility of producing tailor-made tissues of specific composition to suit the repair of a particular tissue type, for example, (1) myocutaneous flaps to replace tissue loss following traumatic injury, (2) bone for nose, digit or joint repair, and (3) fat to provide a bulky flap as required in contour defects of the face and neck. The development of new growth chambers of appropriate body shapes (eg. ears, noses, etc) has significant commercial implications.Read moreRead less
Engineering Tissues And Organs In Vivo From Stem Cells
Funder
National Health and Medical Research Council
Funding Amount
$549,480.00
Summary
Tissue engineering is an exciting new area of medical research. We have developed a unique animal model of tissue engineering where new tissue spontaneously sprouts from the surface of a vascular loop enclosed inside a plastic chamber. The tissue thus created has its own blood supply. By adding cultured cells or altering the environment of the chamber we have been able to grow new specific tissues such as fat and muscle. This technology potentially allows the generation of spare body parts to re ....Tissue engineering is an exciting new area of medical research. We have developed a unique animal model of tissue engineering where new tissue spontaneously sprouts from the surface of a vascular loop enclosed inside a plastic chamber. The tissue thus created has its own blood supply. By adding cultured cells or altering the environment of the chamber we have been able to grow new specific tissues such as fat and muscle. This technology potentially allows the generation of spare body parts to replace lost or worn out organs and tissues. We have recently reproduced this model in the mouse to be able to screen a range of mouse and human stem cells. These cells have the ability to change (i.e. differentiate) into many different types of cell depending on how they are stimulated. In Part 1 of this project we will determine in the mouse chamber the growth characteristics and survival rates of these stem cells. A chamber encapsulating a flowing blood vessel will be implanted subcutaneously in each groin. In one chamber we will inject fluorescently labelled stem cells in a growth medium and in the other growth medium alone. Tissue will be analysed at 1, 2 and 4 weeks. In Part 2 we will inject a variety of Rosa26 labelled mouse stem cells obtained from several different tissues. Through the aid of naturally occurring growth and differentiation factors they will differentiate into one of several different tissues including fat, cartilage, bone, neural tissue, blood vessels, liver, etc, which will be identified by histology and cell culture. In one experiment we will genetically alter cells injected into the chamber so that they produce only skeletal muscle. In Part 3 we will grow new human tissues by injecting human stem cells into the same tissue engineering chambers in mice which will tolerate cells from other mammals (these are known as SCID mice). Success in novel method would be the precursor for the production of new human tissues to repair specific defects.Read moreRead less
In Vivo Tissue Engineering Of Adipose Tissue For Reconstructive Surgery
Funder
National Health and Medical Research Council
Funding Amount
$713,545.00
Summary
We are able to grow vascularised tissue in implanted plastic chambers to a predetermined size and shape in the rat and mouse (NHMRC Project Grant 01-03; #145782; CIA Morrison). The basis of this growth is blood vessel sprouting from the surface of the vessel bundle or loop, followed by synthesis of structural molecules and the migration of surrounding cells into the vascularised network to form a stable tissue. Unlike other in vivo models of tissue engineering, the tissue grows spontaneously and ....We are able to grow vascularised tissue in implanted plastic chambers to a predetermined size and shape in the rat and mouse (NHMRC Project Grant 01-03; #145782; CIA Morrison). The basis of this growth is blood vessel sprouting from the surface of the vessel bundle or loop, followed by synthesis of structural molecules and the migration of surrounding cells into the vascularised network to form a stable tissue. Unlike other in vivo models of tissue engineering, the tissue grows spontaneously and is densely vascularised, enabling continuous growth and surgically transfer to another part of the body, or to another animal. In this renewal application of the above NHMRC grant, we propose to direct these findings towards the development of vascularised fat tissue which would be ideal for reconstructive surgery as a stable, inert tissue filler. Our efforts to grow fat tissue in vivo to date have identified 4 major requirements: a fat precursor cell source; an instructive basement membrane matrix (which may include growth-differentiation factors); space into which the tissue can grow; a stable blood supply. We will focus here on optimising the precursor cell source and instructive matrix to generate vascularised fat tissue around the blood supply we can engender in our tissue engineering chamber. We have found Matrigel, a mouse tumor-derived matrix rich in basement membrane components, to be instructive for growing fat, and will also build on preliminary observations that either muscle or fat tissue can provide the appropriate precursor cells for this process. Finally we propose to adapt and upsize the vascularised fat tissue chamber to the pig, in a step towards human use, and assess its transplantability and longevity. The clinical application of our work is to produce breast reconstruction tissue and lipo filling for contour deformities resulting from trauma, congenital deformity, ageing and cancer surgery, particularly breast reconstruction.Read moreRead less
Outcomes Of The Arterial Switch Operation: A Multi-centre Study
Funder
National Health and Medical Research Council
Funding Amount
$86,733.00
Summary
The arterial switch operation is the surgery of choice for children born with transposition of the great arteries, a congenital heart defect where the main two vessels of the heart arise from wrong pumping chambers of the heart. There are very few studies looking at adults after this operation. We aim to study all patients who have had an arterial switch. The results of this study will further increase our knowledge of the long term consequences of having the arterial switch operation.
Understanding The Mechanisms Of Development And Treatment In Hydrocephalus.
Funder
National Health and Medical Research Council
Funding Amount
$395,914.00
Summary
This project aims to investigate the progressive change in cerebrospinal fluid dynamics, axonal damage and tissue mechanical properties during the development and treatment of hydrocephalus in-vivo. Results from this study is important to elucidate the mechanisms of hydrocephalus and to improve treatment and diagnosis of hydrocephalus.
Detection, Prevention And Treatment Of Failure Of The Fontan Circulation
Funder
National Health and Medical Research Council
Funding Amount
$90,533.00
Summary
Children born with complex heart defects and only one pumping chamber can now live into adulthood with an operation called the Fontan procedure. As this operation has only existed for 40 years, the long-term expectations for these children and young adults are still unclear, and their population is growing every year. This project aims to answer questions about the follow-up and medical management of people living with a Fontan procedure.
Detection Of Liver And Renal Function Abnormalities In The Australian & New Zealand Population Of Fontan Patients
Funder
National Health and Medical Research Council
Funding Amount
$345,080.00
Summary
Children born with complex heart defects and only one pumping chamber can now live into adulthood with an operation called the Fontan procedure. As this operation has only existed for 40 years, the long-term expectations for these children and young adults are still unclear, and their population is growing every year. There is now evidence that they may suffer from liver and kidney failure. This project will identify the severity of liver and kidney damage in our population of Fontan patients.
Refining Methods For Obtaining, Synthesising And Interpreting Research Evidence In Surgery
Funder
National Health and Medical Research Council
Funding Amount
$314,312.00
Summary
Research evidence plays a crucial role in improving clinical care. However the main forms of evidence and the tools that facilitate evidence use - namely randomised controlled trials (RCT) and structured systematic reviews of existing research - have had limited application in surgery for a variety of reasons. This project aims to promote the use of research evidence in surgical decision making by developing tools tailored to the predominance of non-RCTs in surgery and surgeons' information need ....Research evidence plays a crucial role in improving clinical care. However the main forms of evidence and the tools that facilitate evidence use - namely randomised controlled trials (RCT) and structured systematic reviews of existing research - have had limited application in surgery for a variety of reasons. This project aims to promote the use of research evidence in surgical decision making by developing tools tailored to the predominance of non-RCTs in surgery and surgeons' information needs.Read moreRead less
In this Fellowship I will capitalise on my role as Professor of Surgery and Public Health at Monash University, Director of the National Trauma Research Institute, and a surgeon at The Alfred Hospital, to lead a program of research that improves our understanding of what works in trauma care and trauma systems, uses scientific strategies to ensure research makes a difference to practice and policy, and supports further research that seeks to understand how research can best be used to improve in ....In this Fellowship I will capitalise on my role as Professor of Surgery and Public Health at Monash University, Director of the National Trauma Research Institute, and a surgeon at The Alfred Hospital, to lead a program of research that improves our understanding of what works in trauma care and trauma systems, uses scientific strategies to ensure research makes a difference to practice and policy, and supports further research that seeks to understand how research can best be used to improve injured peoples' lives.Read moreRead less