Novel Use of Synthetic Peptide Hydrogel to Improve Outcomes in Adult Tonsillectomy: A Pilot Study

Introduction: RADA-16 is a synthetic peptide hydrogel shown to improve wound healing and hemostasis. We aimed to evaluate the utility of intraoperative RADA-16 application on patient outcomes following adult tonsillectomy.

Methods: This multi-site randomized controlled trial (RCT) and retrospective cohort study was conducted between September 2025 to January 2026. Adult patients undergoing tonsillectomy received either a standard post-operative analgesic regimen or were given intraoperative application of RADA-16 plus the post-operative analgesic regimen. Outcome measures included pain, post tonsillectomy hemorrhage (PTH), emergency department (ED) visits, return to diet, and rescue analgesic usage. Data was collected with surveys and chart review. Longitudinal pain trends were analyzed using linear mixed-effects models. Analgesic burden and return to diet were evaluated via Poisson regression, Cox Proportional Hazards, and Kaplan-Meier. Adverse outcomes were assessed using Fisher’s exact test.

Results: The study included 26 patients: 12 from the RCT and 14 from the retrospective cohort (mean age 29.2; 69% female; 42% Hispanic). 13 patients received RADA-16 and 13 did not. Baseline characteristics, including surgical technique performed and surgical indication, were similar between groups (p>0.05). The RADA-16 group reported significantly lower daily pain scores compared to controls (-16.4 points, p=0.039). RADA-16 patients were 3.16 times more likely to stop opioid use earlier (95%CI 1.24-8.09) and demonstrated a 67% reduction in total opioid consumption (p < 0.001). They also required ibuprofen for significantly fewer days (p=0.026). Dietary recovery was significantly faster in the treatment group (p=0.004); by postoperative day 5, nearly 70% of RADA-16 patients were tolerating soft diet compared to 20% of controls. Though 30-day ED visits and PTH were fewer in the RADA-16 group, this was not statistically significant (p=0.48 and 1.0, respectively).

Conclusions: In adult tonsillectomy, intraoperative application of RADA-16 significantly decreased post-operative pain and quickened recovery.