ArticleTheranostics2014
Luminescent dual sensors reveal extracellular pH-gradients and hypoxia on chronic wounds that disrupt epidermal repair.
Article in Theranostics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 134 citations in OpenAlex.
- Oxygenation Status in Chronic Leg Ulcer After Topical Hemoglobin Application May Act as a Surrogate Marker to Find the Best Treatment Strategy and to Avoid Ineffective Conservative Long-term Therapy.Molecular imaging and biology · 2018Trial
- The Role of Skin Surface pH in Age Associated Pruritus: Mechanistic and Clinical Insights.American journal of clinical dermatology · 2026Review
- Intracellular pH dynamics promotes zebrafish larval tail regeneration.bioRxiv : the preprint server for biology · 2026Article
- Fluorescent Polymeric Nanofibers as Ratiometric Multiplexed Skin Sensors of pH and Oxygen.Advanced healthcare materials · 2026Article
- Article
- Inflammation-Responsive Hydrogels in Perioperative Pain and Wound Management: Design Strategies and Emerging Potential.Gels (Basel, Switzerland) · 2025Review
- Autofluorescence properties of wound-associated bacteria cultured under various temperature, salinity, and pH conditions.BMC microbiology · 2025Article
- ZnO colludes with C. acnes in healing delay and Scar hyperplasia by barrier destruction.Journal of nanobiotechnology · 2025Article
- Assessing Wound Healing in Vivo Using a Dual-Function Phosphorescent Probe Sensitive to Tissue Oxygenation and Regenerating Collagen.ACS applied materials & interfaces · 2025Article
- The Acid-Buffered Engineered Gel Promotes In Vitro Cutaneous Healing and Fights Resistant Bacteria in Wounds.Pharmaceutics · 2024Article
- Wound pH-Modulating Strategies for Diabetic Wound Healing.Advances in wound care · 2024Review
- pH-regulated single cell migration.Pflugers Archiv : European journal of physiology · 2024Review
- Kick-Starting Wound Healing: A Review of Pro-Healing Drugs.International journal of molecular sciences · 2024Review
- Quantification of oxygen consumption in head and neck cancer using fluorescent sensor foil technology.Frontiers in oncology · 2024Article
- Fabrication and evaluation of vitamin doped Zno/AgNPs nanocomposite based wheat gluten films: a promising findings for burn wound treatment.Scientific reports · 2023Article
- Expression of pH-Sensitive TRPC4 in Common Skin Tumors.International journal of molecular sciences · 2023Article
- The Challenges of OInternational journal of molecular sciences · 2022Review
- Investigation of the Mechanism and Chemistry Underlying Staphylococcus aureusJournal of bacteriology · 2022Article
- Tolerance and resistance of microbial biofilms.Nature reviews. Microbiology · 2022Review
- The structure-function relationship of Pseudomonas aeruginosa in infections and its influence on the microenvironment.FEMS microbiology reviews · 2022Review
Corrections and comments
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Authors and funding
22 authors at 7 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Wound repair is a quiescent mechanism to restore barriers in multicellular organisms upon injury. In chronic wounds, however, this program prematurely stalls. It is known that patterns of extracellular signals within the wound fluid are crucial to healing. Extracellular pH (pHe) is precisely regulated and potentially important in signaling within wounds due to its diverse cellular effects. Additionally, sufficient oxygenation is a prerequisite for cell proliferation and protein synthesis during tissue repair. It was, however, impossible to study these parameters in vivo due to the lack of imaging tools. Here, we present luminescent biocompatible sensor foils for dual imaging of pHe and oxygenation in vivo. To visualize pHe and oxygen, we used time-domain dual lifetime referencing (tdDLR) and luminescence lifetime imaging (LLI), respectively. With these dual sensors, we discovered centripetally increasing pHe-gradients on human chronic wound surfaces. In a therapeutic approach, we identify pHe-gradients as pivotal governors of cell proliferation and migration, and show that these pHe-gradients disrupt epidermal barrier repair, thus wound closure. Parallel oxygen imaging also revealed marked hypoxia, albeit with no correlating oxygen partial pressure (pO2)-gradient. This highlights the distinct role of pHe-gradients in perturbed healing. We also found that pHe-gradients on chronic wounds of humans are predominantly generated via centrifugally increasing pHe-regulatory Na+/H+-exchanger-1 (NHE1)-expression. We show that the modification of pHe on chronic wound surfaces poses a promising strategy to improve healing. The study has broad implications for cell science where spatial pHe-variations play key roles, e.g. in tumor growth. Furthermore, the novel dual sensors presented herein can be used to visualize pHe and oxygenation in various biomedical fields.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.