hyperbaric oxygen (HBO) therapy and wound dressing in chronic wound treatment: biotechnological applications

Clinical and experimental studies have widely shown that in diabetic patients wound healing is impaired. Usually, those patients present chronic non healing wounds localised at pressure sites on the foot. So far, the mechanisms implicated in this pathology are still poorly understood: an important role is played by the neurological and vascular disorders; anyway, the diabetic condition itself is associated with the altered wound healing capability. A normal wound healing process requires many consecutive steps: haemostasis, inflammation and cellular infiltration, cell proliferation and granular tissue formation, epithelialization and wound closure. In diabetic patients, wounds exhibit a marked alteration of both inflammation/cell infiltration and cell proliferation/granular tissue formation steps: the progress of wound repair during this phases depends upon a sophisticated interaction between inflammatory cells, biochemical mediators, such as growth factors, extracellular matrix and microenvironmental cell populations. A key role is exerted by fibroblasts, that synthesize and organise most of the extracellular matrix molecules and release in the wound space a variety of growth factors. To realize an optimal environment for the wound healing process, it’s necessary an adequate wound dressing. The dressing design is quite complicate, because needs to ensure that the wound remains moist, free of infections, with an optimal pH and temperature, and must provide an adequate environment for cell survival and proliferation. Usually dressing, besides many inert components, are enriched of antimicrobials, antiseptics, silver-ion impregnated bandages, growth factors, extracellular matrix molecules. The choice of the dressing is usually made on the basis of the type, state and site of the wound, but also on the personal experience and components availability. In wound healing treatment, despite of the importance of an adequate dressing and of the heterogeneity of products available, there have been few clinical and experimental trials to establish the advantages/disadvantages of the different dressings. In the recent years, the importance of the oxygen levels in the wound site has been appreciated. Disruption of microcirculation seems to be the initial event leading to hypoxia, that remains in chronic wound conditions. Several studies reported that in diabetic patients HBO treatment is effective in improving oxygen tension at the wound site. Adequate oxygen tension is needed to sustain cellular metabolism in the wound environment. In particular, immune system cells need oxygen for their antibacterial activity; fibroblast synthesize, modify and deposit collagen only when oxygen is present at rather high partial pressure. Moreover, higher oxygen tension following HBO treatment inhibits anaerobic pathogens proliferation, promotes neoangiogensis, that in turn is crucial to restore optimal tissues oxygenation, and seems to increase the effectiveness of antibiotics. In order to deepen our knowledge about the mechanisms that lead to wound healing impairment in diabetic patients, we decided to prepare an experimenta trial to characterize fibroblasts obtained from chronic wounds tissue fragments. Samples have been obtained from impaired wound healing diabetic patients included in a HBO therapy protocol. Fibroblasts migration and proliferation from the tissue fragments have been evaluated in vitro; moreover, the cells have been exposed in vitro to several wound dressing components. In a successive step, will be measured fibroblasts capability to synthesize and release extracellular matrix molecules (i.e. collagen, CAMs). Evaluating HBO and dressing components effects on the metabolism of the fibroblasts obtained from different patients, will be possible to prepare specific therapeutic protocols that combine HBO therapy/specific dressing designs aimed at improve fibroblast activity and thus chronic wounds healing.