In regenerative endodontic procedures (REPs), it is crucial to find effective materials. This study introduces glycosaminoglycan (GAG) mimetic peptide amphiphile (PA, GAG-PA) and K-PA nanofibers, synthesized to emulate sulfated GAGs, aiming to enhance tissue repair within damaged pulp - an area where standardized protocols are currently lacking. The objective of this study was to investigate the regenerative potential of GAG-PA nanofibers in REP. Heparan sulfate mimicking PAs was designed to develop a bioactive nanofibrous supramolecular system. The cavities on the mesial surfaces of the first upper molars of 8 rats (4 rats in the study group and 4 in the control group) were prepared, and the pulps were perforated. Then, the material was applied onto the dental pulp, and the cavities were closed with a self-curing glass ionomer cement filling material. Physiological saline was used in the control group. Thirty days after application, the teeth were extracted, and the formation of regenerative tissue sections in the pulp was evaluated using hematoxylin and eosin (H&E) staining and Masson's trichrome staining. After 30 days, H&E staining demonstrated robust tissue regeneration in the implanted region, with minimal neutrophil infiltration. Masson's trichrome staining confirmed reparative dentin formation. Quantitative analysis revealed a regeneration percentage of 85% in the study group, compared to 80% in the control group. Statistical analysis showed no significant difference in regeneration between the groups (p > 0.05). Our comprehensive study, utilizing GAG-PA and K-PA nanofibers, demonstrated successful synthesis, characterization and formation of nanofiber networks. The in vivo experiment with rats exhibited substantial tissue regeneration with quantifiable results supporting the efficacy of the nanofiber approach. Statistical analysis confirmed the consistency between the study and control groups, emphasizing the potential of these nanofibers in endodontic tissue regeneration applications.
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