January 19, 2021

IBAL Formulation Topical Application Wound Healing and Low pH levels References

The pH of wounds during healing and infection: a descriptive literature review


Review found evidence to suggest that wound pH, and specifically an ‘Alkaline pH’, is conducive to bacterial bio-burden and reflective of the specific physiological processes of the healing cascade. The pH of a wound is also involved in the development and management of a biofilm. This is evidenced by identifying that bacteria increased biofilm growth in an alkaline environment. It has also been shown that once established biofilms become resistant to fluctuations in pH they can survive in pH ranges that would normally be inhibitory to growth under planktonic conditions.


The relationship between pH and wound healing


In intact dermal tissue (i.e. effectively sealed from the environment by the epidermis), the products of oxidative respiration, CO 2 and anaerobic respiration (lactic acid), are removed from the local environment by the return flow of venous blood. An indicator of this is the lower pH of venous blood (7.35) compared to that of arterial blood (7.45). The pH of intact skin ranges from about 4.8 to 6.0, while the interstitial fluid exhibits a near neutral pH. The low skin pH is attributed mainly to the presence of the so-called "acid mantle," a natural barrier to the external environment.


Acidic Environment and Wound Healing: A Review


Applying acids to the wound surface lowers the pH of the infected surfaces and makes an environment unsuitable for the growth and multiplication of the bacteria. This has been proved by microbiological studies and the rapid clearing up of infected surfaces. Application of acid is effective in clearing bacterial pathogens from contaminated or infected wound beds by creating an acidic environment unfavorable for the growth of bacterial pathogens present on the wound surface.


The effects of pH on wound healing, biofilms, and antimicrobial efficacy


pH has been shown to affect matrix metalloproteinase activity, tissue inhibitors of matrix metalloproteinases activity, fibroblast activity, keratinocyte proliferation, microbial proliferation, and also immunological responses in a wound; the patient's defense mechanisms change the local pH of a wound to effect microorganism invasion and proliferation; this pH change has been found to affect the performance of antimicrobials, and therefore the efficacy in biological environments directly relevant to wound healing. Based on the available body of scientific evidence to date, it is clear that pH has a role to play in both the healing of and treatment of chronic and acute wounds.


Influence of pH on wound-healing: a new perspective for wound-therapy?


The pH value within the wound-milieu influences indirectly and directly all biochemical reactions taking place in this process of healing. Investigations have shown that in fact some healing processes such as the take-rate of skin-grafts require an alkaline milieu. The conclusion to be drawn at present is that the wound pH indeed proves to be a potent influential factor for the healing process and that different pH ranges are required for certain distinct phases of wound healing. 


The significance of surface pH in chronic wounds


The pH environment also influences oxygen release to the tissues. Oxygen delivery to damaged tissue particularly in the chronic wound is dependent not only on perfusion but diffusion. A lowering of pH by 0.6 units releases almost 50% more oxygen and a five-fold increase in release of oxygen by a shift of 0.9 pH units. Within the chronic wound this is important as the likelihood of healing is high if tissue oxygen tension (pO2 ) is >40mmHg, but is unlikely at levels of <20mmHg. 


Functional Regulation of the Plasma Protein Histidine-Rich Glycoprotein by Zn2+ in Settings of Tissue Injury


The observed Zn2+binding to histidine-rich glycoprotein appears to regulate its function at sites pertaining to wound healing and is mediated through the pH and Zn2+-sensing ability of the histidine-rich region. It is evident that the large number of proposed HRG ligands cannot be accommodated simultaneously, therefore it is plausible the HRR may finely tune individual interactions by modifying the native or cleaved form of HRG by altering its conformational structure through the charged state of histidine, induced by acidic pH or binding to Zn2+. The HRR may therefore act as the regulatory module throughout each of the wound-healing stages and hence restrict the type of ligand interactions that can take place to facilitate biological processes that contribute to efficient tissue regeneration.


Endothelial Antioxidant-1: a Key Mediator of Copper-dependent Wound Healing in vivo


Cu chaperone Antioxidant-1 (Atox1) in the cytosol supplies Cu to the secretory enzymes such as lysyl oxidase (LOX), while Atox1 in the nucleus functions as a Cu-dependent transcription factor. Using mouse cutaneous wound healing model, here we show that Cu content (by X-ray Fluorescence Microscopy) and nuclear Atox1 are increased after wounding, and that wound healing with and without Cu treatment is impaired in Atox1−/− mice. Endothelial cell (EC)-specific Atox1−/− mice and gene transfer of nuclear-target Atox1 in Atox1−/− mice reveal that Atox1 in ECs as well as transcription factor function of Atox1 are required for wound healing.


Recent advances in topical wound care


Hydrogels are polymers, glycerine or water-based gels, impregnated gauzes or sheet dressings. Their high water content does not allow them to absorb large amount of exudates so they cannot be used on heavy exuding wounds. They have a gentle yet effective debriding and desloughing action by rehydrating necrotic tissue and removing it without damaging healthy tissue and absorbing slough and exudates. They rehydrate the wound bed, reduce pain because of their cooling effect, are non-adhesive, fill dead spaces, are easy to apply and remove.[30–32] They are best suited for dry wounds or those with minimal exudates. But they require a secondary dressing.


pH-Dependent Metal Ion Toxicity Influences the Antibacterial Activity of Two Natural Mineral Mixtures


Recent studies have demonstrated that several mineral products sold for medicinal purposes demonstrate antimicrobial activity, but little is known about the physicochemical properties involved in antibacterial activity. We conclude that the acidic environment of the hydrated minerals significantly contributes to antibacterial activity by increasing the availability and toxicity of metal ions. These findings provide impetus for further investigation of the physiological effects of mineral products and their applications in complementary antibacterial therapies.


The Effect of pH on the Extracellular Matrix and Biofilms


The pH profiles of healthy skin, acute wounds, and chronic wounds differ significantly. Chronic wounds have an alkaline pH whereas healthy skin has a slightly acidic pH. Although there is evidence on the effect of pH on protease production and bacterial proliferation in wounds, there is little evidence to show its effect on ECM synthesis and degradation.

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