Abstract
Chronic wounds are a significant socioeconomic problem for governments worldwide. Approximately 15% of people who suffer from diabetes will experience a lower-limb ulcer at some stage of their lives, and 24% of these wounds will ultimately result in amputation of the lower limb. Hyperbaric Oxygen Therapy (HBOT) has been shown to aid the healing of chronic wounds; however, the causal reasons for the improved healing remain unclear and hence current HBOT protocols remain empirical. Here we develop a three-species mathematical model of wound healing that is used to simulate the application of hyperbaric oxygen therapy in the treatment of wounds. Based on our modelling, we predict that intermittent HBOT will assist chronic wound healing while normobaric oxygen is ineffective in treating such wounds. Furthermore, treatment should continue until healing is complete, and HBOT will not stimulate healing under all circumstances, leading us to conclude that finding the right protocol for an individual patient is crucial if HBOT is to be effective. We provide constraints that depend on the model parameters for the range of HBOT protocols that will stimulate healing. More specifically, we predict that patients with a poor arterial supply of oxygen, high consumption of oxygen by the wound tissue, chronically hypoxic wounds, and/or a dysfunctional endothelial cell response to oxygen are at risk of nonresponsiveness to HBOT. The work of this paper can, in some way, highlight which patients are most likely to respond well to HBOT (for example, those with a good arterial supply), and thus has the potential to assist in improving both the success rate and hence the cost-effectiveness of this therapy.
Highlights
Chronic leg ulceration is a significant socioeconomic problem [1]
There is much debate about the best way to treat these wounds, and one treatment that is shrouded with controversy is Hyperbaric Oxygen Therapy (HBOT)
There are currently no conclusive data showing that HBOT can assist chronic wound healing, but there has been some clinical success
Summary
Chronic leg ulceration is a significant socioeconomic problem [1]. Those who suffer from leg ulcers experience considerable pain, immobility and decreased quality of life [2]. A successfully healing wound (or an ‘‘acute’’ wound) is typically thought to progress through four stages; haemostasis, inflammation, proliferation and remodelling [4,5], these processes are interconnected and overlapping. Inflammation sees the production of chemoattractants that stimulate fibroblasts, the dominant cell in the proliferative stage of healing, to migrate into the wound site and to produce collagen, the main component of the extracellular matrix (ECM). The joining of two capillary sprouts within a healing wound forms a loop through which blood can flow and new sprouts develop from this vessel propagating angiogenesis [7]
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