In Vitro Evidence for Oral Soft Tissue Regenerative Effects of a Polynucleotide-Hyaluronan Formulation.
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BORIS DOI
Publisher DOI
PubMed ID
41252639
Description
Objectives
We aimed to investigate the effects of a polynucleotide-hyaluronan (PN-HA) formulation on human palatal fibroblasts (HPFs) and oral epithelial cells (OKF6/TERT-2) to assess its potential application in oral soft tissue reconstructive procedures.Material And Methods
The impact of PN-HA on cell viability, migration, and proliferation was assessed using functional assays. Gene expression of wound healing-related growth factors, inflammatory cytokines, and keratinization markers was evaluated by qRT-PCR, while protein expression and kinase signaling were analyzed via immunofluorescence and immunoblotting.Results
PN-HA preserved cell viability and significantly (p < 0.05) enhanced migration of both HPFs and OKF6/TERT-2 compared to untreated control cells. While it significantly (p < 0.01) increased proliferation in HPFs, no direct proliferative effect was observed in OKF6/TERT-2 monocultures. In HPFs, PN-HA upregulated TGFB1, PDGFB, and FGF2 genes encoding the respective pro-migratory/pro-proliferative growth factors, whereas TGFB3 and EGF were selectively induced in OKF6/TERT-2. PN-HA markedly increased pro-inflammatory cytokine expression and activated p38 MAPK signaling in epithelial cells, alongside ERK1/2 activation and moderate increase in adenosine A2A receptor expression in both cell types. A pronounced upregulation of keratinocyte differentiation markers was observed at both mRNA and protein levels. Notably, in epithelial-fibroblast cocultures, PN-HA significantly (p < 0.01) enhanced epithelial proliferation, likely mediated by increased FGF7 and HGF expression in fibroblasts.Conclusions
PN-HA promotes oral fibroblast migration and proliferation, induces epithelial differentiation, and stimulates epithelial proliferation in coculture with fibroblasts. The observed cell- and context-specific effects highlight the potential of PN-HA to support soft tissue regeneration and keratinization in periodontal reconstructive surgeries.
We aimed to investigate the effects of a polynucleotide-hyaluronan (PN-HA) formulation on human palatal fibroblasts (HPFs) and oral epithelial cells (OKF6/TERT-2) to assess its potential application in oral soft tissue reconstructive procedures.Material And Methods
The impact of PN-HA on cell viability, migration, and proliferation was assessed using functional assays. Gene expression of wound healing-related growth factors, inflammatory cytokines, and keratinization markers was evaluated by qRT-PCR, while protein expression and kinase signaling were analyzed via immunofluorescence and immunoblotting.Results
PN-HA preserved cell viability and significantly (p < 0.05) enhanced migration of both HPFs and OKF6/TERT-2 compared to untreated control cells. While it significantly (p < 0.01) increased proliferation in HPFs, no direct proliferative effect was observed in OKF6/TERT-2 monocultures. In HPFs, PN-HA upregulated TGFB1, PDGFB, and FGF2 genes encoding the respective pro-migratory/pro-proliferative growth factors, whereas TGFB3 and EGF were selectively induced in OKF6/TERT-2. PN-HA markedly increased pro-inflammatory cytokine expression and activated p38 MAPK signaling in epithelial cells, alongside ERK1/2 activation and moderate increase in adenosine A2A receptor expression in both cell types. A pronounced upregulation of keratinocyte differentiation markers was observed at both mRNA and protein levels. Notably, in epithelial-fibroblast cocultures, PN-HA significantly (p < 0.01) enhanced epithelial proliferation, likely mediated by increased FGF7 and HGF expression in fibroblasts.Conclusions
PN-HA promotes oral fibroblast migration and proliferation, induces epithelial differentiation, and stimulates epithelial proliferation in coculture with fibroblasts. The observed cell- and context-specific effects highlight the potential of PN-HA to support soft tissue regeneration and keratinization in periodontal reconstructive surgeries.
Date of Publication
2025-12
Publication Type
Article
Subject(s)
Keyword(s)
connective tissue grafts
•
growth factors
•
hyaluronic acid
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oral soft tissue wound healing
•
polynucleotides
Language(s)
en
Contributor(s)
Mladenova, Ina | University of Bern |
Asparuhova Maria B. | University of Bern |
Additional Credits
University of Bern
University of Bern
Series
Clinical and Experimental Dental Research
Publisher
Wiley
ISSN
2057-4347
Access(Rights)
open.access