Abstract
Previous research studies have clearly shown that failure of foot ulcer healing can eventually lead to amputation. It is therefore important that the diagnosis and treatment of ulcers is both timely and effective. Two major classes of regulators of extracellular matrix (ECM) – growth factors and the group of enzymes termed matrix metalloproteinases (MMPs) – and their effect on healing diabetic wounds are the focus of this study. A number of animal models of wound healing are also discussed, with the aim of developing strategies to improve the rate of tissue repair in diabetes.

Abstract
Wound healing is a complex physiological process; hence a reproducible in vitro model of skin provides a valuable tool to further understand the biology of dermal wound repair and to investigate techniques to improve wound healing. Human skin equivalent models (HSEs) have been proposed to serve as an in vitro model for these purposes; however, there is currently no readily available HSE model in Australia.
In this study, we describe the production of a HSE obtained by seeding human keratinocytes onto a de-epidermised dermis, (DED) which was then submerged in medium for 3 days and subsequently cultured at the air-liquid interface for up to 20 days. The model was characterised morphologically and biochemically over the 20 days of culture at the air-liquid interface and showed histological features similar to those observed in an in vivo epidermis. Immunohistochemistry of the epidermal markers keratin 6, keratin 14, keratins 1/10/11 and the basement membrane marker collagen type IV, revealed typical differentiation. The HSE was then examined for its potential as a burn wound healing model. Burn wounds were created in the model and the re-epithelialisation of the wounds was followed for 6 days by keratinocyte morphology; metabolic activity was analysed every 2 days. Keratinocytes began to migrate into the wound bed after 2 days and continued to migrate for the next 4 days, suggesting that the HSEs generated may be of great value for studies of the wound healing process and for the evaluation of new therapies.

Abstract
The specific involvement of individual cell types in wound repair is generally well understood. How cells interact with each other at the wound site and what effect this has on their healing-related functions, however, is not so clear. To begin exploring the influence cell-cell interactions have on wound healing, this article examines how inflammatory T cells effect skin fibroblast and keratinocyte function. Our studies show that T cells can reduce collagen production by fibroblasts and induce programmed cell death (apoptosis) in keratinocytes, with both of these outcomes having the potential to impair healing. Given that a number of different cell types are present in a wound, the challenge is to identify the cell-cell interactions that are beneficial and those that are detrimental to healing so they can be manipulated appropriately to promote repair.

Abstract
Activated protein C (APC) is a serine protease that plays a central role in physiological anticoagulation and has, more recently, been shown to be a potent anti-inflammatory mediator. Recent work in our lab shows that APC upregulates expression and activation of matrix metalloproteinase-2 (MMP-2), an enzyme that plays a prominent role during angiogenesis in cultured human skin fibroblasts (HF), endothelial cells and keratinocytes (HK). Furthermore, APC promotes the migration and proliferation of these cells in vitro. In a full-thickness rat skin healing model, APC enhances wound healing compared to saline control. In summary, our results demonstrate that APC promotes cutaneous wound healing at least partly by upregulating MMP-2 activity, increasing angiogenesis, promoting re-epithelialisation and dampening inflammation. These unique properties of APC make it an attractive therapeutic agent to promote the healing of chronic wounds.

Abstract
The sex hormones oestrogen and testosterone are important mediators of wound repair. Oestrogen enhances wound healing by reducing inflammation and enhancing matrix production. However, in post-menopausal women, when oestrogen levels are decreased, wound healing is impaired and susceptibility to chronic non-healing wounds increases. Surprisingly, although the speed of healing is impaired, an improvement in the quality of scarring is observed. Testosterone, in contrast, inhibits wound repair and is associated with enhanced inflammation.
One of the most important consequences of hormonal changes is the age-related delay in cutaneous wound healing observed in both males and females, which leads to substantial morbidity and mortality. Manipulation of hormone levels may provide alternative treatments for promoting healing in non-healing wounds and may be of value in promoting reduced scarring

Abstract
The actin cytoskeleton is an essential network of filaments found in all cells and is important in the process of migration, adhesion and proliferation. All these processes are fundamental to wound repair. Members of the gelsolin family of actin-severing proteins are important regulators of cytoskeletal organisation. Manipulation of these proteins has revealed important roles in wound repair, suggesting that they may be potential new targets for therapeutic intervention to help improve wound healing and reduce scar formation.