Self-assembling RADA16 peptide hydrogel supports hemostasis, synechiae reduction, and wound healing in a sheep model of endoscopic nasal surgery

Objectives: Complications of endoscopic sinus/nasal turbinate surgery include postoperative hemorrhage, synechiae formation, and poor wound healing. Our primary objectives were to evaluate whether a topical hydrogel based on self-assembling RADA16 peptides: i) reduces bleeding and synechiae formation, and ii) supports wound healing, using a sheep nasal surgery model. Methods: Thirty sheep received endoscopic surgery-created bilateral nasal mucosal injuries on the middle turbinate/opposing septum. Injuries were randomly assigned RADA16, Gelatin-thrombin, or no treatment. Outcomes included intra-operative hemostasis, scar tissue/synechiae formation and wound healing at 2 weeks and the 6-week study terminus, and histopathology. Results: Intra-operative hemostasis time improved with RADA16 and Gelatin-thrombin versus Control wounds (139.7 +/- 56.2 s, 145.4 +/- 58.1 s, and 224.0 +/- 69.9 s, respectively; p < 0.0001 for both comparisons). Two-week synechiae scores (maximum 4 points) were similar in Controls (2.9 +/- 1.8 points) and Gelatin-thrombin (3.1 +/- 1.6 points) wounds ( p > 0.05), but were reduced in RADA16 sites by 91% versus Controls and 92% versus Gelatin-thrombin treatment (0.3 +/- 0.6 points; p < 0.0001 for both comparisons). Six-week synechiae scores were similar in Control (1.1 +/- 1.7 points) and Gelatin-thrombin (1.7 +/- 2.0 points) wounds ( p > 0.05), but reduced 100% in RADA16-treated wounds. Synechiae occurred in fewer RADA16-treated sites at 2 weeks (20%) versus Gelatin-thrombin (80%) and Controls (75%; p < 0.01) and at 6 weeks (0%, 50% and 35%, respectively; p < 0.01). RADA16 was associated with significantly lower 6-week histopathology scores, driven by reduced submucosal fibrosis and angiogenesis.Conclusion: Although RADA16 and Gelatin-thrombin similarly accelerated hemostasis in this sheep endoscopic sinus surgery model, only RADA16 reduced postoperative synechiae formation at 2 weeks with an absence of synechiae at 6 weeks. Histology suggested RADA16 enhanced mucosal regeneration.(c) 2022 Japanese Society of Otorhinolaryngology-Head and Neck Surgery, Inc. Published byElsevier B.V.This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ )