Interaction between patient-administered adjunctive palatal topical hyaluronic acid and smoking status in free gingival grafting: a retrospective cohort study

Free gingival graft (FGG) harvesting is frequently associated with postoperative morbidity, driving the search for effective adjunctive agents. This retrospective, non-randomised cohort study evaluated the clinical outcomes associated with the use of topical Hyaluronic Acid (HA) gel on palatal donor site healing and patient-reported morbidity following FGG procedures in both smokers (S +) and non-smokers (S-). Distinct from the sub-dressing application methods commonly reported in the literature, this study evaluated a practical, patient-administered protocol to assess its real-world clinical utility. Eighty non-randomised patients requiring FGG were categorised into four groups based on smoking status and HA usage ( n = 20 per group). The experimental groups applied 0.2% HA gel to the donor site via digital massage three times daily for 14 days. Recipient site (graft shrinkage %) and donor site (VAS-pain, epithelialisation %) parameters were assessed over 3 months. Results were evaluated at a p < 0.05 significance level. Significantly thicker baseline palatal soft tissue thickness (PSTT) was observed in the control group ( p = 0.003) compared to the S-G + and S + G + subgroups, indicating a potential confounder. However, covariate adjustment (ANCOVA) confirmed that paradoxical donor site outcomes, significantly higher Day 3 pain ( p = 0.002) and delayed epithelialisation at Day 14 and 1 month ( p < 0.05) in the S-G + subgroup, persisted after adjusting for baseline PSTT. At the recipient site, graft shrinkage was not significantly correlated with smoking status or daily consumption, generating the hypothesis of a potential ‘threshold effect’ rather than a dose-dependent relationship. FGG yielded stable recipient site outcomes irrespective of smoking status. Conversely, at the donor site, the observed performance of topical HA appeared protocol-dependent. Within the limits of this retrospective cohort, the 'real-world' regimen of patient-administered digital massage was associated with higher pain and delayed recovery in non-smokers, associations that persisted after statistical adjustment for baseline PSTT and serve to generate the hypothesis of a potential application-related mechanical effect. Consequently, to minimise mechanical irritation whilst ensuring therapeutic benefit, future research should investigate whether atraumatic application methods (e.g., syringe delivery) can optimise outcomes compared to manual massage. These findings suggest that developing novel, atraumatic applicators could be a key focus for subsequent clinical trials. ClinicalTrials.gov NCT07143760. Registered retrospectively on 19/08/2025, representing a limitation in prospective reporting transparency.