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

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.