Skin Preconditioning Before Ablative Er:YAG Exposure Is Associated with a Different Temporal Cutaneous Recovery Trajectory: An Exploratory, Randomized, Vehicle-Controlled Split-Neck Study of 7% Ectoine

Background: This study investigated whether topical preconditioning with 7% ectoine modifies the cutaneous recovery trajectory following ablative Er:YAG laser treatment. Methods: In this exploratory proof-of-concept, randomized, vehicle-controlled split-neck study (retrospectively registered, ISRCTN69645337, 26 August 2026; no publicly time-stamped statistical analysis plan), 30 adults with Fitzpatrick phototype II applied 7% ectoine or its identical vehicle to opposite sides of the neck for 7 or 14 days before standardized Er:YAG treatment. Biophysical and 48 MHz ultrasound parameters were assessed through day 7. OBSERV 520x imaging was performed at baseline and on day 7, with CIELAB analysis comparing baseline and day 7. Results: Significant intervention-by-time interactions were observed for TEWL, hydration, pH, and erythema (all p < 0.0001). Immediately after treatment, ectoine-preconditioned skin showed higher TEWL and a small temperature difference (+0.150 °C). At 24 h, erythema, pH, and low-echogenic pixel content (LEP) were lower with ectoine (median LEP: 0.222% vs. 2.015%; p < 0.000001). By day 7, ectoine was associated with lower TEWL, erythema, pH, and LEP and higher hydration. Day-7 CIELAB analysis showed a smaller increase in a* (between-side difference: −0.64; p < 0.000001). Procedural pain was low (NRS: 1.60 ± 0.62), with no documented adverse events. Extending preconditioning to 14 days provided no consistent additional benefit. Conclusions: Ectoine-containing preconditioning was associated with differences across several complementary instrumental recovery outcomes. These exploratory, hypothesis-generating findings support further investigation of pre-procedural skin conditioning in prospectively registered studies.