Abstract
Fibrosis and scar formation is a medical condition observed under various circumstances, ranging from skin wound healing to cardiac deterioration after myocardial infarction. Among other complex interdependent phases during wound healing, fibrosis is associated with an increased fibroblast to myofibroblast transition. A common hypothesis is that decreasing the pH of non-healing, alkaline wounds to a pH range of 6.0 to 6.5 increases healing rates. A new material-based strategy to change the pH by use of electronic ion pumps is here proposed. In contrast to passive acidic wound dressings limited by non-controlled delivery kinetics, the unique electronic ion pump design and operation enables a continuous regulation of pH by H+ delivery over prolonged durations. In an in vitro model, fibroblast to myofibroblast differentiation is attenuated by lowering the physiological pH to an acidic regime of 6.62 ± 0.06. Compared to differentiated myofibroblasts in media at pH 7.4, gene and protein expression of fibrosis relevant markers α-smooth muscle actin and collagen 1 is significantly reduced. In conclusion, myofibroblast differentiation can be steered by controlling the pH of the cellular microenvironment by use of the electronic ion pump technology as new bioelectronic drug delivery devices. This technology opens up new therapeutic avenues to induce scar-free wound healing.
Highlights
The wound healing process is characterised by highly complex and interdependent phases, involving haemostasis, inflammation, migration, proliferation, and maturation
By using a second electronic ion pump to physically separate the counter electrode from the cell culture, we could guarantee the cytocompatibility of the system and did not impose potential additional effects arising from e.g. metallic counter electrodes or Ag/AgCl electrodes directly immersed in the cell culture well
We could demonstrate that fibroblast to myofibroblast differentiation can be steered by controlling the environmental pH to 6.5
Summary
The wound healing process is characterised by highly complex and interdependent phases, involving haemostasis, inflammation, migration, proliferation, and maturation. In addition to primary effects such as low healing rates or secondary effects such as bacterial infection, skin wound fibrosis and pronounced scar formation present a high prevalence, affecting over 100 million patients each year [3]. These effects cause significant physical and psychological distress to individual patients, in particular after occurrence of burn wound contractures [4], and impose a high financial burden to the healthcare system. It is crucial to achieve a functional technology for wound healing, which expresses therapeutic factors in a dynamic and highly addressable fashion in order to optimise efficacy, and to minimise scar formation
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