Controlling pH by electronic ion pumps to fight fibrosis
| Autor: | Anne Géraldine Guex, Markus Rottmar, Katharina Maniura-Weber, Daniel Simon, David J. Poxson, René M. Rossi, Giuseppino Fortunato, Magnus Berggren |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Skin wound
Chemistry Medical Biotechnology 02 engineering and technology 010402 general chemistry 021001 nanoscience & nanotechnology medicine.disease 01 natural sciences 0104 chemical sciences Collagen type I alpha 1 medicine.anatomical_structure Ion pump Fibrosis Drug delivery medicine Biophysics General Materials Science Medicinsk bioteknik 0210 nano-technology Fibroblast Wound healing Myofibroblast Myofibroblasts pH Electronic ion pumps |
| Popis: | 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 alpha-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. (C) 2021 The Authors. Published by Elsevier Ltd. Funding Agencies|Novartis Foundation for Medical-Biological ResearchUK Research & Innovation (UKRI)Biotechnology and Biological Sciences Research Council (BBSRC) [18C144]; Swedish Foundation for Strategic ResearchSwedish Foundation for Strategic Research; Knut and Alice Wallenberg FoundationKnut & Alice Wallenberg Foundation; VinnovaVinnova |
| Databáze: | OpenAIRE |
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