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. 2025 Sep;20(9):365-373.
doi: 10.1080/17460751.2025.2567177. Epub 2025 Sep 29.

The effects of polynucleotides-based biomimetic hydrogels in tissue repair: a 2D and 3D in vitro study

Maria Teresa Colangelo  1 , Stefano Guizzardi  1 , Luana Laschera  1 , Marco Meleti  2 , Carlo Galli  1
Affiliations

The effects of polynucleotides-based biomimetic hydrogels in tissue repair: a 2D and 3D in vitro study

Maria Teresa Colangelo et al. Regen Med. 2025 Sep.

Abstract

Introduction: Biomimetics offers promising tools to improve wound healing in difficult clinical conditions. Polynucleotides (PN) show high potential for tissue repair in oral and periodontal surgery, by relying on the body's inherent self-healing capabilities. The aim of the present study was to elucidate in vitro the effects of Odonto-PN (O-PN) and Regenfast (REG), two PN-based compounds, on oral tissue repair.

Methods: We employed 3D spheroid cultures and cell scratch assays to simulate wound healing in vitro, assessing cell migration and morphology under normal conditions and following mitomycin-induced inhibition of cell growth.

Results: Both O-PN and REG supported early cell viability and spheroid disassembly. O-PN supported the initial outgrowth of fibroblasts, whereas REG enhanced sustained cell migration at later time points. In scratch assays, REG effectively facilitated defect closure - even under mitomycin treatment - and induced a more elongated, migratory cell phenotype.

Conclusions: These findings suggest that both O-PN and REG can favorably modulate fibroblast function to support wound repair. While O-PN fosters early activation and cell viability, REG exerts potent pro-migratory effects that may be particularly useful for complex periodontal regeneration. Their selective use could provide valuable adjuncts in clinical protocols aimed at restoring delicate oral structures, such as the interdental papillae.

Keywords: Polynucleotides; cell movement; cell shape; fibroblasts; wound healing.

Plain language summary

When gums are damaged or need surgery, healing can be slow and difficult and support therapies may be required. We investigated two hydrogels made from DNA fragments called polynucleotides. One treatment contains only polynucleotides (O-PN). The other mixes polynucleotides with hyaluronic acid, a natural substance in the body (REG). We grew gingival cells in the lab and tested how these treatments helped them. We asked two questions: do the treatments help cells stay alive early on, and do they help cells move into and close a wound-like gap? These hydrogels work mainly as a physical support for cells. By holding water and creating a soft, elastic environment similar to living tissue, they provide a moist surface where cells can attach, stay alive, and move. We found that O-PN helped cells stay active and spread around clusters of cells in the first days, while REG helped cells move farther and faster to close gaps. Importantly, this effect happened even when we used mitomycin c, a compound capable of stopping cells from dividing. This shows that REG affects cell movement, not just cell growth. These results suggest that O-PN may be most useful to support cell viability, while REG may help move cells into difficult areas to close defects, such periodontal pockets. This invitro study clarifies how these clinically used compounds act at the cellular level and will help refine their use and guide future protocol improvements in clinical practice.

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Conflict of interest statement

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

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