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Peer-reviewedCC BYInternational journal of molecular sciences

Poly-L-Lactic Acid Attenuates Fibrotic Remodeling During Cutaneous Wound Healing

  • Kyung-A Byun1,2,3
  • Hyoung Moon Kim1,2,4
  • Seyeon Oh2,3
  • Ki Woong Yu1,2,5
  • Ji Min Lee6
  • Kuk Hui Son7
  • Kyunghee Byun1,3,8
8 affiliations
  1. 1Department of Anatomy & Cell Biology, College of Medicine, Gachon University, Incheon 21936, Republic of Korea
  2. 2Functional Cellular Networks Laboratory, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon 21999, Republic of Korea
  3. 3LIBON Inc., Incheon 22006, Republic of Korea
  4. 4Maylin Apgujeong Clinic, Seoul 06024, Republic of Korea
  5. 5Maylin Clinic Jamsil Lotte Hotel Branch, Seoul 05554, Republic of Korea
  6. 6Director Global Clinic Gangnam, Seoul 06611, Republic of Korea
  7. 7Department of Thoracic and Cardiovascular Surgery, Gachon University Gil Medical Center, Gachon University, Incheon 21565, Republic of Korea
  8. 8Department of Health Sciences and Technology, Gachon Advanced Institute for Health & Sciences and Technology (GAIHST), Gachon University, Incheon 21999, Republic of Korea
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Abstract

Pathological hypoxia following cutaneous injury is a critical driver of wound chronicity and fibrotic remodeling. The nuclear receptor binding SET domain protein 2 (NSD2)/lysine demethylase 2A (KDM2A)–histone H3 lysine 36 dimethylation (H3K36me2) axis is a known regulator of hypoxia-induced epithelial-to-mesenchymal transition (EMT) in malignancy; however, its role in skin repair remains largely unexplored. We investigated whether poly-L-lactic acid (PLLA) could attenuate fibrotic remodeling by modulating the NSD2/KDM2A–H3K36me2 axis and examining angiogenic signaling. We used a murine 9 mm punch-wound model for in vivo assessment and HaCaT keratinocytes and human dermal fibroblasts (HDFs) exposed to 2% O2 as in vitro hypoxia models. PLLA was administered to evaluate its impact on angiogenic signaling, collagen architecture, and the NSD2/KDM2A pathway. PLLA was associated with increased angiogenic markers and reduced expression of several hypoxia-associated epigenetic and fibrotic markers. In mice, PLLA increased vascular endothelial growth factor (VEGF)/VEGF receptor 2 expression and blood vessel abundance. In addition, PLLA decreased NSD2 and H3K36me2 levels while increasing KDM2A levels. Histological analysis showed less dense collagen staining and a change in the collagen type I/type III staining ratio, alongside a smaller photographically defined residual lesion area. Under controlled hypoxic conditions in vitro, PLLA suppressed EMT-related transcription factors, including Snail, Slug, and Twist, in keratinocytes and attenuated transforming growth factor-β1/phosphorylated mothers against decapentaplegic homolog 2/3 signaling and α-smooth muscle actin expression in fibroblasts. These findings support further study of PLLA-associated changes in vascular, epithelial, and fibrotic markers during wound remodeling.

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Cite

BibTeXRIS
BibTeX
@article{byun2026polyllactic,
  title = {{Poly-L-Lactic Acid Attenuates Fibrotic Remodeling During Cutaneous Wound Healing}},
  author = {Kyung-A Byun and Hyoung Moon Kim and Seyeon Oh and Ki Woong Yu and Ji Min Lee and Kuk Hui Son and Kyunghee Byun},
  journal = {International journal of molecular sciences},
  year = {2026},
  month = oct,
  doi = {10.3390/ijms27198874},
  url = {https://europepmc.org/article/PMC/PMC13665362},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Poly-L-Lactic Acid Attenuates Fibrotic Remodeling During Cutaneous Wound Healing
AU  - Kyung-A Byun
AU  - Hyoung Moon Kim
AU  - Seyeon Oh
AU  - Ki Woong Yu
AU  - Ji Min Lee
AU  - Kuk Hui Son
AU  - Kyunghee Byun
PY  - 2026
DA  - 2026/10/01
JO  - International journal of molecular sciences
DO  - 10.3390/ijms27198874
UR  - https://europepmc.org/article/PMC/PMC13665362
AB  - Pathological hypoxia following cutaneous injury is a critical driver of wound chronicity and fibrotic remodeling. The nuclear receptor binding SET domain protein 2 (NSD2)/lysine demethylase 2A (KDM2A)–histone H3 lysine 36 dimethylation (H3K36me2) axis is a known regulator of hypoxia-induced epithelial-to-mesenchymal transition (EMT) in malignancy; however, its role in skin repair remains largely unexplored. We investigated whether poly-L-lactic acid (PLLA) could attenuate fibrotic remodeling by modulating the NSD2/KDM2A–H3K36me2 axis and examining angiogenic signaling. We used a murine 9 mm punch-wound model for in vivo assessment and HaCaT keratinocytes and human dermal fibroblasts (HDFs) exposed to 2% O2 as in vitro hypoxia models. PLLA was administered to evaluate its impact on angiogenic signaling, collagen architecture, and the NSD2/KDM2A pathway. PLLA was associated with increased angiogenic markers and reduced expression of several hypoxia-associated epigenetic and fibrotic markers. In mice, PLLA increased vascular endothelial growth factor (VEGF)/VEGF receptor 2 expression and blood vessel abundance. In addition, PLLA decreased NSD2 and H3K36me2 levels while increasing KDM2A levels. Histological analysis showed less dense collagen staining and a change in the collagen type I/type III staining ratio, alongside a smaller photographically defined residual lesion area. Under controlled hypoxic conditions in vitro, PLLA suppressed EMT-related transcription factors, including Snail, Slug, and Twist, in keratinocytes and attenuated transforming growth factor-β1/phosphorylated mothers against decapentaplegic homolog 2/3 signaling and α-smooth muscle actin expression in fibroblasts. These findings support further study of PLLA-associated changes in vascular, epithelial, and fibrotic markers during wound remodeling.
SN  - 1422-0067
ER  -