Effect of Probiotic Limosilactobacillus reuteri and Hyaluronic Acid Gel Combination Therapy on Neutrophil Response, Neovascularization, and Reepithelialization in the Wound-Healing Process Following Tooth Extraction: An In Vivo Study

Abstract This study aimed to analyze the effects of supportive therapy using a combination of Limosilactobacillus reuteri (L. reuteri) and hyaluronic acid (HA) gel on the wound-healing process during inflammatory, proliferative, and remodeling/maturation phases following tooth extraction. Forty-five white Wistar rats (Rattus norvegicus) were divided into five treatment groups after the left mandibular central incisor was extracted. The experimental groups were treated with HA gel, probiotic L. reuteri gel, a combination of HA gel and L. reuteri gel, and povidone-iodine (PVP-I). The negative control group was treated with sterile tampons. Tissue samples were collected on days 3, 7, and 14 post-tooth extractions and analyzed histologically using hematoxylin–eosin (HE) staining to evaluate neutrophil numbers, neovascularization, and epithelial thickness. Data analysis was performed using IBM SPSS version 29. Inter-rater reliability was tested using the intraclass correlation coefficient (ICC), followed by normality and homogeneity tests. For normally distributed data, parametric hypothesis testing was conducted using one-way ANOVA at a 95% confidence level (p < 0.05). The post hoc least significant difference test was used to observe significant differences between the groups. Significant differences in neutrophil numbers, neovascularization, and re-epithelialization were found between the negative control and combination group (p < 0.05) on days 3, 7, and 14. HA and L. reuteri combination therapy is effective in accelerating wound healing after tooth extraction.