CLINICAL NONINVASIVE METHODS OF ASSESSING HEALING INCLUDE:

     - Scanning laser Doppler measurement of blood supply (angiogenesis).

     - Ultrasound structural evaluation of quality of healing.

COLLABORATIVE PROGRAMMES:

The institute has a major international collaborative arrangement with universities in China (Xi'an, Beijing, Wuhan) and Vietnam (Hanoi); this has resulted in a number of joint publications ranging from the epidemiology of chronic wounds in China to the effect of traditional wound healing agents on cell metabolism.

EDUCATIONAL PROGRAMMES

The unit has organised a number of educational wound healing programmes ranging from symposia on different aspects of healing to International congresses including two of the annual European Tissue Repair Society's meetings, one of which was the first meeting of the Society in 1991. International meetings in China, Thailand, Vietnam in conjunction with Europe have been organised by the Wound Healing Institute.

OXFORD -BASED WOUND HEALING EDUCATIONAL PROGRAMMES

A number of wound healing educational programmes are organised by the institute each year, a major one being the Oxford-European Wound Healing Summer School.

Further details of the Summer School will follow soon.

WOUND HEALING PRECLINICAL RESEARCH FACILITIES

Cell Culture Laboratory

Another major part of our programme has been the studies carried out in the cell culture laboratory under the direction of Dr Margaret Hughes.

We see the role of this programme as fourfold, carrying out experimental studies, clinical treatment, service to other researchers including Industry, and teaching cell culture techniques.

Need for experimental in vitro work

As inferred in the title of one journal: ATLA (Alternatives To Laboratory Animals), there is an increasing need to find alternative ways of performing pre-clinical studies for the testing of new treatments for many conditions, including problems of abnormalities in or the failure of wound healing. Animal tests have become a very emotive issue. Apart from this, they allow only a limited number of observations, are expensive to carry out and, in spite of many common factors, there may be wide species differences in biochemistry and metabolites. In vitro cell culture studies allow the use of human tissue and many varieties of tissue can be investigated. In the wound healing laboratory we use skin cells, culturing mainly fibroblasts, keratinocytes, melanocytes. It is important to realise that cells from neo-natal donors are not necessarily equivalent to adult cells in their response to growth factors, hormones or other chemicals. Failure to take account of this fact has led to some false generalisations being made by some groups in the past. Because of availability, many of our studies have used normal skin cells, but it is realised that the phenotypes differ, and some studies have used wound cells. While there is an outlay in setting up equipment and in maintenance, the ongoing costs should be less than for animals. Vast numbers of cells can be produced from a very small piece of tissue. Some types of cells, such as fibroblasts, can be passaged many times and still retain their principal characteristics. For example, high passage wound fibroblasts continue to induce a greater contraction of collagen than normal skin fibroblasts from the same patient. Vials of cells can be cryopreserved and used for repeat or different studies later. Obviously there are also limitations to using cultured cells which are in an isolated closed system, in a much simpler environment than the complex milieu in vivo, and one must beware of making oversimplified extrapolations to the in vivo situation.

Experimental Research

Our experimental research focuses on using cultured cells to investigate some of the processes involved in wound healing. Proliferation of cells is important in several stages of wound healing and we use in vitro models to examine some of the mechanisms involved in wound healing, e.g., fibroblast-populated collagen lattices to study contraction/contracture; a scratch technique to study re-epithelialization. We have investigated the effects of drugs such as minoxidil and tamoxifen as well as some traditional remedies. The results of which have been published in scientific journals.

Burn trauma and wounds are a major problem in many developing countries and traditional medicines play a large role in their treatment. We have investigated the effects of some herbal remedies from China, Vietnam and even from UK in some of our in vitro wound models. Thus we have been able to show significant stimulation of fibroblast and keratinocyte proliferation and of keratinocyte migration by Eupolin, a plant extract licensed for clinical use in Vietnam. In addition, this extract inhibited contraction by fibroblasts in the collagen lattice model which has led to the suggestion that those using it clinically should monitor the quality of scarring to see if this is improved with Eupolin treatment.

In relation to the microenvironment of wounds we have studied the effects of wound fluid from leg ulcer patients, both on the growth of normal fibroblasts and on the potential degradation of growth factors using a fibroblast strain for bio-assay. In collaborative studies, colleagues from the Clinical Biochemistry Department have been investigating the composition of wound fluid from healing and non-healing leg ulcers. The aim of this work is to develop useful clinical markers as predictors of healing and nonhealing wounds.

Cell culture clinical treatment

We have grown both allogeneic (from Transplant Centre donors) and autologous keratinocytes without feeder layers, either as epithelial sheets or as monolayers on various polymeric materials for the treatment of leg ulcer patients and for some preparatory studies for potential clinical use.

INDUSTRIAL

We have cooperated with various industrial companies in the investigation of materials for tissue engineering, determining the in vitro toxicity, and the ability of material to carry cells and/or allow the proliferation of cells. We have also studied the effect of some debriding agents on normal human skin samples in vitro prior to clinical evaluation.

ONGOING WORK:

Ongoing experimental studies include the investigation of the effects of changing physical parameters, including warming. In addition the culture of tissue from hypertrophic scars and keloids to obtain cells for use in the various wound healing models is being used to extend in vitro work on therapeutic agents such as Tamoxifen, which we have previously shown to inhibit collagen lattice contraction by normal human fibroblasts.

WOUND HEALING CLINICAL THERAPEUTIC STUDIES

The institute carries out clinical trials on dressings, growth factors, tissue engineered skin equivalents and other new therapies for the treatment of wounds. This is a major part of the Institute's programme.