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Article Navigation >  CHINESE JOURNAL OF BURNS AND WOUNDS  >  > Accepted Manuscript
Song Wei,Zhang Chao,Kong Yue,et al.Effects of polyvinyl alcohol-boric acid-based functionalized hydrogels on human skin fibroblasts and HaCaT cells[J].Chin J Burns Wounds,2026,42(3):1-10.DOI: 10.3760/cma.j.cn501225-20250825-00365.
Citation: Song Wei,Zhang Chao,Kong Yue,et al.Effects of polyvinyl alcohol-boric acid-based functionalized hydrogels on human skin fibroblasts and HaCaT cells[J].Chin J Burns Wounds,2026,42(3):1-10.DOI: 10.3760/cma.j.cn501225-20250825-00365.
shu

Effects of polyvinyl alcohol-boric acid-based functionalized hydrogels on human skin fibroblasts and HaCaT cells

doi: 10.3760/cma.j.cn501225-20250825-00365
  • 1.

    Key Laboratory of Photochemical Conversion and Optoelectronic Materials, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing 100190, China

  • 2.

    University of Chinese Academy of Sciences, Beijing 100049, China

  • 3.

    Research Center for Wound Repair and Tissue Regeneration, Medical Innovation Research Department, the PLA General Hospital, Beijing 100048, China

Funds:

General Program of National Natural Science Foundation of China 82471049, 82472166, 32471432, 52073293, 52273160

More Information
  • Corresponding author: Niu Zhongwei, Email: niu@mail.ipc.ac.cn
  • Received Date: 2025-08-25
    Available Online: 2026-03-03
    Abstract
  •   Objective  To investigate the effects of polyvinyl alcohol-boric acid (PVA-BA)-based functionalized hydrogels on human skin fibroblasts (HSFs) and HaCaT cells, providing experimental evidences for subsequent in vivo studies on wound repair and clinical translation of this hydrogel system.  Methods  This study was designed as a grouped and factorial experimental investigation. Based on PVA-BA, a freeze-thaw cycling method was employed to prepare PVA-BA hydrogel, PVA-BA-S hydrogel loaded with a final molarity of 5 μmol/L SB431542, and PVA-BA-B hydrogel loaded with a final molarity of 1 μmol/L BML-284. Fourier transform infrared spectroscopy and X-ray diffraction were employed to characterize the characteristic absorption peaks and diffraction patterns of the above-mentioned hydrogels. The drug release of PVA-BA-S hydrogel and PVA-BA-B hydrogel in phosphate-buffered saline (PBS) with pH values of 5.5 and 7.4 was detected using a liquid chromatography, and the cumulative drug release rate at 48 hours of immersion was calculated. According to the random number table method, HSFs were divided into control group with conventional culture, activation-only group with conventional culture after treatment with recombinant human transforming growth factor-β1 (TGF-β1) protein for 24 hours, as well as PVA-BA group and PVA-BA-S group cultured with PVA-BA hydrogel extract and PVA-BA-S hydrogel extract, respectively, after treatment with recombinant human TGF-β1 protein for 24 hours. After 24 hours of culture, mRNA expression levels of TGF-β pathway-related factors α-smooth muscle actin (α-SMA), TGF-β, Smad2, Smad3, type Ⅰ collagen (COL Ⅰ), COL Ⅲ in HSFs were detected using real-time fluorescence quantitative reverse transcription polymerase chain reaction. Protein expression levels of COL Ⅰ and COL Ⅲ in HSFs were assessed via the immunofluorescence method. According to the random number table method, HaCaT cells were divided into control group with conventional culture, PVA-BA group cultured with PVA-BA hydrogel extract, and PVA-BA-B group cultured with PVA-BA-B hydrogel extract. After 24 hours of culture, mRNA expression levels of Wnt pathway-related factors β-catenin, matrix metalloproteinase-9 (MMP-9), E-cadherin, N-cadherin in HaCaT cells were detected by real-time fluorescence quantitative reverse transcription polymerase chain reaction. The protein expression level of keratin 5 was evaluated by the immunofluorescence method. Except for characterization, the sample size for each experiment was 3.  Results  The Fourier transform infrared spectroscopy spectra of the PVA-BA hydrogel, PVA-BA-S hydrogel, and PVA-BA-B hydrogel all exhibited stretching vibration peaks corresponding to C-O and B-O bonds within the B-O-C group at wavenumbers of 1 100 and 1 450 cm⁻¹, and X-ray diffraction patterns all showed a sharp diffraction peak at around 20°. At 48 hours of immersion, the cumulative drug release rate of PVA-BA-S hydrogel in PBS at pH 5.5 was (70.9±2.3)%, which was significantly higher than (60.0±2.2)% in PBS at pH 7.4 (t=6.02, P<0.05); the cumulative drug release rate of PVA-BA-B hydrogel in PBS at pH 5.5 was (83.9±2.2)%, which was significantly higher than (65.2±1.7)% in PBS at pH 7.4 (t=11.63, P<0.05). After 24 hours of culture, the mRNA expression levels of TGF-β, COL Ⅰ, COL Ⅲ, and Smad3 of HSFs in PVA-BA-S group were significantly higher than those in control group (P<0.05), the mRNA expression levels of TGF-β, COL Ⅰ, COL Ⅲ, α-SMA, Smad2, and Smad3 were significantly lower than those in activation-only group and PVA-BA group (P<0.05), and the protein expression levels of COL Ⅰ and COL Ⅲ of HSFs in PVA-BA-S group were significantly lower than those in activation-only group and PVA-BA group (P<0.05). After 24 hours of culture, compared with those in control group and PVA-BA group, the PVA-BA-B group showed significantly increased mRNA expression levels of β-catenin, MMP-9, and N-cadherin (P<0.05) and a significantly decreased mRNA expression level of E-cadherin (both P values <0.05) in HaCaT cells; the protein expression level of keratin 5 of HaCaT cells in PVA-BA-B group was significantly higher than that in control group and PVA-BA group (both P values <0.05).  Conclusions  PVA-BA-S hydrogel and PVA-BA-B hydrogel based on the PVA-BA can effectively inhibit the fibrotic phenotype of activated HSFs and enhance the migratory ability of HaCaT cells by regulating the TGF-β pathway and Wnt pathway, respectively, providing a novel drug delivery strategy for functional wound healing.

     

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