Journal article
Ti3C2Tx MXene augments osmo-adaptive repression of the inflammatory stress response for improved wound repair
Nanoscale, v 17(20), pp 12758-12774
23 May 2025
PMID: 40314768
Abstract
Chronic non-healing wounds represent a growing global health challenge that is poorly addressed by current advances in wound care dressings. Hyperosmotic stress linked, for example, to poor glycaemic control, is a known but under-investigated contributor to the chronic wound environment and a known inflammatory stimulus. MXene (Ti3C2Tx) has been considered for smart dressing applications but has not been investigated for use with bioactive agents to directly moderate hyperosmotic stress for improved wound care. In this study, Ti3C2Tx, in combination with osmolyte betaine, was used to investigate hyperosmotic stress-induced effects on wound closure. The effect of these materials was measured using a wound closure scratch assay, and data was used to mathematically model changes in HaCaT human keratocyte migratory rate and velocity. Changes in the upregulation of apoptotic and inflammatory markers were measured, and qualitative changes in phalloidin-labelled actin cytoskeletal structure were observed. A tert-butyl glycine betainate (tBu-GB) polyacrylate microgel loaded Ti3C2Tx dressing was then fabricated and tested for biocompatibility and slow elution of osmolyte over time. Osmotic stress at levels that did not induce cell death reduced the migratory capacity of keratocytes to close the scratch. Migration by osmotically stressed keratocytes was reduced by more than 50% at 24 h and remained at 65% (+/- 5%) at 48 h compared to complete scratch closure at 24 h in the cell only control. This reduction was reversed by a Ti3C2Tx coating, allowing complete scratch closure by 48 h in the osmotically stressed group. Exposure of osmotically stressed cells to betaine increased normalised wound closure in the osmotically stressed keraotycte group at each time point and this was augmented by the presence of a Ti3C2Tx coating. Osmotic stress induced upregulation of inflammatory markers IL-6, IL-1 alpha, IL-1 beta, CXCL1, and CXCL8 by at least 10-fold. The effect was significantly greater in the presence of bacterial LPS and this was significantly reduced by the presence of Ti3C2Tx alone and in combination with betaine. Sustained and slow release of betaine was demonstrated from a tBu-GB-microgel loaded Ti3C2Tx dressing over 48 h supporting the use of such dressings to improve osmotic stress induced, poor wound closure rates.
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Details
- Title
- Ti3C2Tx MXene augments osmo-adaptive repression of the inflammatory stress response for improved wound repair
- Creators
- Sertan Kiziloz - Univ Brighton, Ctr Regenerat Med & Devices, Sch Appl Sci, Brighton BN2 4GJ, EnglandEmma J. Ward - Univ Brighton, Ctr Regenerat Med & Devices, Sch Appl Sci, Brighton BN2 4GJ, EnglandDaniel Hawthorne - Univ Brighton, Ctr Regenerat Med & Devices, Sch Appl Sci, Brighton BN2 4GJ, EnglandAvick Sinha - Univ Brighton, Ctr Regenerat Med & Devices, Sch Appl Sci, Brighton BN2 4GJ, EnglandGrace Cooksley - UCL GOS Inst Child Hlth, Dev Biol & Canc DBC Res & Teaching Dept, London WC1N 1EH, EnglandDipak Sarker - Univ Brighton, Ctr Regenerat Med & Devices, Sch Appl Sci, Brighton BN2 4GJ, EnglandCyril Crua - Univ Sussex, Sch Engn & Informat, Brighton BN1 9QJ, EnglandAndrew Lloyd - Univ Brighton, Ctr Regenerat Med & Devices, Sch Appl Sci, Brighton BN2 4GJ, EnglandChristopher E. Shuck - Rutgers State Univ, Dept Chem & Chem Biol, Piscataway, NJ 08854 USAYury Gogotsi - Drexel University, Materials Science and EngineeringSusan Sandeman (Corresponding Author) - University of Brighton
- Publication Details
- Nanoscale, v 17(20), pp 12758-12774
- Publisher
- Royal Society of Chemistry
- Grant note
- EPSRC; UK Research & Innovation (UKRI); Engineering & Physical Sciences Research Council (EPSRC) EP/W023164/1 / University of Brighton
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Materials Science and Engineering
- Web of Science ID
- WOS:001480101500001
- Scopus ID
- 2-s2.0-105004217638
- Other Identifier
- 991022048372404721