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There has been little understanding of acidification functionality in wound healing, highlighting the need to study the efficacy of wound acidification on wound closure and cellular activity in non-infected wounds. This study is focused on establishing the healing potential of wound acidification in non-infected wounds. Acidic buffers, constituting either phosphoric or citric acid, were employed to modify the physiological pH of non-infected full-thickness excisional murine wounds. Acidification of the wound by acidic buffers was found to be an effective strategy to improve wound healing. A significant improvement in wound healing parameters was observed as early as 2 days post-treatment with acidic buffers compared to controls, with faster rate of epithelialization, wound closure and higher levels of collagen at day 7. pH is shown to play a role in mediating the rate of wound healing, with acidic buffers formulated at pH 4 observed to stimulate faster recovery of wounded tissues than pH 6 buffers. Our study shows the importance of maintaining an acidic wound microenvironment at pH 4, which could be a potential therapeutic strategy for wound management. Refereed/Peer-reviewed

Thesis (PhD(Pharmaceutical Science))--University of South Australia, 2022. Includes bibliographical references. This dissertation established pH as an important factor in enhancing wound healing. Altering wound microenvironment with low molarity acidic buffers at pH 4 increased proliferation and migration of skin cells in vitro. A time-dependent effect was also observed with once-every-second-day treatment significantly improved cell proliferation and migration in vitro. These findings were further proven in vivo, with pH 4 acidic buffers showing excellent wound recovery as early as 2-days post treatment with evidence of increased re-epithelialization, wound contracture, and upregulation of collagen levels. A hydrogel formulation was then developed using natural chitosan and citric acid buffer system, showing excellent anti-microbial activity and enhanced cell growth, presenting a potential wound management formulation for treating both infected and un-infected chronic wounds.

Refereed/Peer-reviewed Strategies that alter the pH of wounds to improve healing outcomes are an emerging area of interest. Currently, there is limited understanding of the effect of hydrogen (H+) on the functionality of skin cells during proliferation and migration, highlighting the need for research to determine the effect of pH during wound healing. This study aimed to determine the effect of acidification on the metabolic activity and migration of human immortalized keratinocytes (HaCaT) and human foreskin fibroblasts (HFF). In vitro models were used with phosphoric and citric acid buffers at a pH range between 3 and 7. Our results showed that cells were more viable in buffers with low rather than high ionic strength. A time-dependent effect of the acidification treatment was also observed with cell metabolic activity varying with treatment duration and frequency. Our results showed that a 24 h treatment and subsequent resting phase significantly improved cell proliferation and migration. This in vitro study is the first to establish a correlation between the role of acidic pH, molarity and treatment regimen in cellular activity. Our data demonstrated a positive effect of acidic pH on cell metabolic activity and migration rate, suggesting a clinical potential in indications such as wound healing.