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Synergistic protective and regenerative effects of hyaluronic acid and polynucleotides against UVA-induced oxidative stress in dermal fibroblasts
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  • Published: 30 January 2026

Synergistic protective and regenerative effects of hyaluronic acid and polynucleotides against UVA-induced oxidative stress in dermal fibroblasts

  • Trang Thanh Thien Tran1,2 na1,
  • Soon Chul Heo1,3 na1,
  • Jun Hee Lee1,2,3,4,5,6 &
  • …
  • Hae-Won Kim1,2,3,4,5,6 

Scientific Reports , Article number:  (2026) Cite this article

We are providing an unedited version of this manuscript to give early access to its findings. Before final publication, the manuscript will undergo further editing. Please note there may be errors present which affect the content, and all legal disclaimers apply.

Subjects

  • Cell biology
  • Diseases
  • Medical research
  • Molecular biology

Abstract

Ultraviolet A (UVA) radiation, a principal driver of skin photoaging, generates excessive reactive oxygen species (ROS) in dermal fibroblasts, causing oxidative stress, loss of viability, inflammatory signaling, and extracellular matrix (ECM) degradation. Hyaluronic acid (HA) and polynucleotides (PN) are clinically used dermal biomaterials; however, their protection against UVA injury remains insufficiently defined. We evaluated HA, PN, and their combination in human dermal fibroblasts (HDFs) subjected to photodamage. HDFs were pretreated with HA, PN, or both, irradiated with 20 J/cm2 UVA, and then maintained in treated media to mimic therapeutic recovery. UVA reduced viability and proliferation, downregulated ECM genes (COL1A1, FN1), and increased intracellular and mitochondrial ROS and proinflammatory cytokine gene (TNF-α). Monotherapy partially alleviated these changes. In contrast, combined HA + PN synergistically improved survival and proliferation, lowered ROS to near baseline, restored ECM transcription, and upregulated antioxidant enzymes (GPX1, SOD2). HA + PN also increased fibroblast invasion, indicating regenerative activity beyond cytoprotective effects. Under basal conditions, neither HA nor PN showed cytotoxicity or prooxidant effects, while modestly enhancing ECM transcription. These findings demonstrate that HA and PN act synergistically to counter UVA-induced oxidative stress and support dermal regeneration, highlighting a combinatorial bioactive strategy for photoaged skin.

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Data availability

The data of this study are available from the corresponding author upon reasonable request.

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Acknowledgements

The authors acknowledge the technical assistance and constructive discussions provided by colleagues during this study.

Funding

This study was supported by the National Research Foundation and funded by the Korean Government (grant number: RS-2022-NR072135).

Author information

Author notes

  1. Trang Thanh Thien Tran and Soon Chul Heo have contributed equally to this work

Authors and Affiliations

  1. Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan, 31116, Republic of Korea

    Trang Thanh Thien Tran, Soon Chul Heo, Jun Hee Lee & Hae-Won Kim

  2. Department of Nanobiomedical Science and BK21 Four NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan, 31116, Republic of Korea

    Trang Thanh Thien Tran, Jun Hee Lee & Hae-Won Kim

  3. Mechanobiology Dental Medicine Research Center, Dankook University, Cheonan, 31116, Republic of Korea

    Soon Chul Heo, Jun Hee Lee & Hae-Won Kim

  4. Department of Nanobiomedical Science and BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan, 31116, Republic of Korea

    Jun Hee Lee & Hae-Won Kim

  5. Department of Biomaterials Science, College of Dentistry, Dankook University, Cheonan, 31116, Republic of Korea

    Jun Hee Lee & Hae-Won Kim

  6. Department of Regenerative Dental Medicine, College of Dentistry, Dankook University, Cheonan, 31116, Republic of Korea

    Jun Hee Lee & Hae-Won Kim

Authors
  1. Trang Thanh Thien Tran
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  2. Soon Chul Heo
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Contributions

Trang Thanh Thien Tran and Soon Chul Heo : Conceptualization, Data curation, Formal Analysis, Investigation, Methodology, Visualization, Writing—original draft. Jun Hee Lee and Hae-Won Kim : Funding acquisition, Project administration, Supervision, Validation, Visualization, Writing—review and editing. All authors read and approved the final manuscript.

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Correspondence to Jun Hee Lee or Hae-Won Kim.

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Tran, T.T.T., Heo, S.C., Lee, J.H. et al. Synergistic protective and regenerative effects of hyaluronic acid and polynucleotides against UVA-induced oxidative stress in dermal fibroblasts. Sci Rep (2026). https://doi.org/10.1038/s41598-026-37730-5

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  • Received: 02 October 2025

  • Accepted: 23 January 2026

  • Published: 30 January 2026

  • DOI: https://doi.org/10.1038/s41598-026-37730-5

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Keywords

  • Ultraviolet A
  • Oxidative stress
  • Human dermal fibroblasts
  • Hyaluronic acid
  • Polynucleotides
  • Dermal regeneration
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