Developing In Vivo Methods Of Adipose Tissue Engineering
Funder
National Health and Medical Research Council
Funding Amount
$374,703.00
Summary
Surgical repair and replacement of soft tissues after tumour removal or to repair existing damage requires fat tissue with a good blood supply. Tissue engineering allows us to create new fat grafts for replacement tissue without causing unnecessary pain or trauma to the patient. We have developed a method for growing fat tissue using a chamber to maintain a space for the tissue to grow into, a blood vessel to supply nutrients to the growing tissue, cells or tissue from the host to encourage cell ....Surgical repair and replacement of soft tissues after tumour removal or to repair existing damage requires fat tissue with a good blood supply. Tissue engineering allows us to create new fat grafts for replacement tissue without causing unnecessary pain or trauma to the patient. We have developed a method for growing fat tissue using a chamber to maintain a space for the tissue to grow into, a blood vessel to supply nutrients to the growing tissue, cells or tissue from the host to encourage cell growth and migration and a matrix or scaffold to support the developing tissue and guide it to form the type of tissue we want (fat, muscle etc). We have shown that the tissue graft may cause fat to grow due to causing an inflammatory reaction and confirmed this by adding a mild inflammatory compound to the chamber instead of a tissue graft. This compound caused the chamber to grow fat tissue. The aim of this project is to determine which of the growth factors or other signaling factors released by the inflammation process is responsible for causing fat tissue production and to identify what cells are being attracted to the chamber to help grow the fat, so that we can further improve our engineering of fat tissue. Understanding the pathways which mediate or stimulate fat growth will provide new opportunities for improving fat growth and allow the engineering of larger fat grafts in larger animals and eventually human clinical application. Beyond that, inflammation is involved in many disease processes (eg. obesity, metabolic syndrome, diabetes, cancer), and these fields of study will also benefit from our research.Read moreRead less
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
Optimizing Implanted Cell Survival Using A Tissue Engineering Model
Funder
National Health and Medical Research Council
Funding Amount
$589,175.00
Summary
Cell therapy and tissue engineering involve the insertion of specific cells into damaged tissues or into a bioraector in a patient's body to generate new replacement tissues. This project seeks to improve two factors associated with inserting cells : 1. The innate survival characteristics of the cells being inserted, and 2. The blood vessel supply at the site of insertion. These techniques will greatly improve the survival of inserted cells.
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
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.
Improved Ex-vivo Culture Of Keratinocytes For Clinical Applications
Funder
National Health and Medical Research Council
Funding Amount
$275,203.00
Summary
Skin cells grown for clinical applications currently require animal-derived cells and-or non-defined products for their expansion in the laboratory; these reagents can potentially infect patients who receive these therapies. This project will identify the essential components provided by these reagents and develop a fully synthetic and defined culture system. This improvement will provide safer, cost-effective grafts and cell-based therapies that will benefit patients suffering burns and wounds.
Reevaluation Of The Anatomy Of The Human Lymphatic Vessel Network
Funder
National Health and Medical Research Council
Funding Amount
$539,750.00
Summary
The mode of spread of cancer cells from a primary tumour to other parts of the body is still not completely understood, although the lymphatic system is known to be important in this process. Lymph vessels are tiny transparent channels that form a network over the entire body. They transport tissue fluid to regional lymph glands in the neck, armpits, groin, chest and abdomen where the immune response maybe initiated to combat foreign agents such as bacteria and cancer cells. Current knowledge of ....The mode of spread of cancer cells from a primary tumour to other parts of the body is still not completely understood, although the lymphatic system is known to be important in this process. Lymph vessels are tiny transparent channels that form a network over the entire body. They transport tissue fluid to regional lymph glands in the neck, armpits, groin, chest and abdomen where the immune response maybe initiated to combat foreign agents such as bacteria and cancer cells. Current knowledge of the anatomy of these tiny vessels is based on work done by Sappey more than a century ago. There is an urgent need to update this work as many of his conclusions have been found to be inaccurate. We will use our pioneering methods of microsurgical tissue transfer- now being used worldwide - and our extensive experience in delineating fine channels, to address some of the basic questions about the anatomical pathways of spread of cancer. We hope to discover for example: why cancer on one side of the back can spread to glands in the opposite groin or armpit, thought by Sappey to be impossible; why cancer on one side of the tongue can spread to lymph glands on the opposite side of the neck; and why there is sometimes swelling of the limbs following lymph gland ablation by surgery or radiotherapy of glands in the groin or armpit. Currently it is thought that the only major connections with the venous system are at the base of the neck. Our initial work has shown unexpected connections with blood vessels in the periphery and unreported lymphatic vessel pathways between the skin and deep tissues. The results of this research will give information that will aid in localizing and treating the spread of malignancies and will underlie future treatment of obstructed lymph vessels that are the cause of painful, disabling swelling (lymphoedema) of the limbs.Read moreRead less
Three Dimensional Ex Vivo Modelling Of Neuromuscular Junction Formation
Funder
National Health and Medical Research Council
Funding Amount
$120,253.00
Summary
Re-establishing functional connections between neurons and muscle is an important step in the recovery process after neuromuscular injury or surgery. In order to study the connection forming process in isolation a biological model of nerve muscle connection formation is required. This study aims to buid a biological model consisting of neurons and muscles in a three dimensional environment and to assess the quality of the functional connections that develop.