Controlling pH by electronic ion pumps to fight fibrosis. (March 2021)

• Record Type: Journal Article
• Authors: Guex, Anne Géraldine; Poxson, David J.; Simon, Daniel T.; Berggren, Magnus; Fortunato, Giuseppino; Rossi, René M.; Maniura-Weber, Katharina; Rottmar, Markus
• Is Part Of: Applied materials today. Volume 22(2021)
• Publication Date: 2021-03
• Subjects: Fibrosis -- Myofibroblasts -- pH -- Electronic ion pumps -- Drug delivery; Materials science -- Periodicals; Materials -- Research -- Periodicals; 620.1105
• DOI: 10.1016/j.apmt.2021.100936
• Languages: English
• ISSNs: 2352-9407

Abstract

Highlights: Controlled proton delivery by electronic ion pumps reduces pH to 6.5. An acidic environment attenuates myofibroblast differentiation (hallmark of fibrosis). A materials-based approach to reduce scar formation. 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. Graphical abstract: Image, graphical abstract