Blue Light for Donor Site Healing in Burn Patients

Burn injuries frequently require surgical treatment with split-thickness skin grafting. This procedure involves harvesting skin from a healthy area of the body, commonly referred to as the donor site (DS). Although donor sites are considered superficial wounds, their healing process can be associated with clinically relevant complications, including delayed re-epithelialization, pain, inflammation, and risk of infection. These complications may prolong hospitalization, negatively affect patient comfort and quality of life, and influence the overall outcome of burn management. Therefore, strategies that may accelerate DS healing while maintaining safety and tolerability are of considerable clinical interest.

Photobiomodulation with blue light (BL) has emerged as a promising therapeutic approach in the management of several types of skin wounds. Experimental and clinical evidence suggests that BL may exert antimicrobial effects, modulate inflammatory processes, and stimulate tissue repair mechanisms involved in wound healing. These biological effects could potentially support faster re-epithelialization and improved wound bed conditions. However, clinical evidence specifically addressing the role of BL therapy in DS healing among burn patients remains limited.

This clinical investigation aims to evaluate the clinical effectiveness and safety of BL photobiomodulation when used in addition to the Standard of Care (SoC) for the treatment of DS wounds in patients undergoing skin grafting for burn injuries.

Study Design The study is designed as an interventional, controlled, prospective, single-center post-market clinical study. The intervention involves the use of a CE-marked medical device (EmoLED) that emits blue light and is already approved and routinely used in clinical practice in accordance with the manufacturer's indications and applicable regulatory standards.

The study will enroll 25 patients with intermediate or deep burn injuries who require surgical treatment with split-thickness skin grafting and who present at least two DS areas suitable for comparative evaluation.

To reduce inter-individual variability and improve the internal validity of the study, an intra-patient controlled design will be used. Each participant will serve as their own control. Two donor site areas will be assigned to different treatment modalities:

• Experimental treatment: SoC plus BL therapy
• Control treatment: SoC alone In the study protocol, the DS on the right will receive the experimental treatment (SoC + BL), while the DS on the left will receive the SoC only. This design allows a direct comparison of clinical outcomes between the two treatment strategies within the same patient, minimizing the influence of patient-specific variables such as age, comorbidities, systemic inflammatory response, and nutritional status.

Study Procedures The day of the surgical intervention will be considered Day 0, during which the Case Report Form (CRF) will be prepared and baseline patient data will be collected. The DS areas will be measured and documented, including photographic documentation.

The experimental treatment with BL will begin at the first postoperative dressing change (Day 2) and will be repeated once per week for a total treatment duration of approximately 3-4 weeks, depending on the healing progression. BL will be applied to the entire donor site area for 60 seconds during each session using the study device.

DS assigned to the control arm will receive only the SoC, according to the wound care procedures routinely applied at the study center.

Clinical evaluation of both DS will be performed weekly during the treatment period, including completion of the CRF and collection of relevant clinical data. Each evaluation will include:

• direct clinical observation of the wound
• completion of validated clinical assessment scales
• structured patient interview when feasible
• laboratory reporting of skin swab results when performed
• standardized photographic documentation of donor site areas The treatment phase is expected to last approximately 30 days, or until complete re-epithelialization of the DS. After wound healing, participants will undergo follow-up visits at 1 month and 3 months to evaluate the quality of the resulting scars and monitor potential late adverse events. When patients are discharged from the hospital before completion of follow-up, these assessments will be performed at the dedicated outpatient clinic of the study unit.

Data Sources and Data Collection

Data collected during the study will originate from source documents, including:

• hospital medical records
• clinical assessment scales
• photographic documentation
• laboratory reports (skin swab analysis)
• paper or electronic Case Report Forms (CRFs) Data will initially be recorded in paper CRFs and subsequently entered into an electronic database for analysis. Immediate completion of the CRF at the end of each visit will be encouraged to reduce missing or incomplete data.

Data Quality Assurance

Several procedures will be implemented to ensure data validity, accuracy, and completeness, including:

• cross-checking between medical records and CRFs to verify data consistency
• double data entry when digital transcription is performed, in order to minimize transcription errors
• standardized training of all members of the research team on study procedures and data collection methods
• periodic monitoring of CRFs by the study monitor to verify completeness and data quality
• systematic archiving of clinical photographs identified by patient code To ensure the reliability of visual assessments, photographic documentation will be reviewed by at least two trained clinical operators, who will independently evaluate wound characteristics and healing progression.

Safety Monitoring Safety assessments will be conducted throughout the study in accordance with standard clinical practice and the study protocol.

The following safety parameters will be monitored:

• occurrence of adverse events (AE) potentially related to blue light exposure
• occurrence of serious adverse events (SAE) during the treatment and follow-up periods

Potential local adverse reactions to BL therapy may include:

• sensation of warmth or heat
• skin irritation
• erythema
• itching or rash

All AE and SAE will be documented in the CRF, including:

• date of onset and resolution
• severity
• suspected relationship to the treatment
• clinical outcome AE will be collected at each dressing change and at any additional time when the patient reports symptoms or complications. Serious adverse events will be reported within 24 hours from the time they become known to the investigator, in accordance with applicable regulatory requirements.

Based on currently available evidence and the safety profile of the device, no specific risks related to study participation are anticipated beyond those associated with standard wound care procedures.

Protocol Deviations All protocol deviations will be identified, documented, and managed in compliance with Good Clinical Practice (GCP) and applicable regulatory requirements.

Potential deviations may include:

• Incorrect allocation of DS areas (experimental vs control). An inadvertent inversion between treated and control areas could occur. In such cases, the deviation will be documented and the analysis will be corrected according to the actual treatment administered. To prevent this error, DS will be clearly labeled and photographed at the time of the first treatment.
• Missed or delayed follow-up visits. Some participants may not attend the scheduled follow-up visits at 1 or 3 months. In these cases, attempts will be made to reschedule the visit whenever possible. Reminder phone calls and scheduling flexibility will be implemented to improve adherence. If follow-up data cannot be recovered, the missing information will be handled as missing data during statistical analysis.
• Missed application of blue light therapy. If the experimental treatment is not applied during a scheduled dressing change due to logistical or operational issues, the treatment will be administered at the next dressing session without excluding the wound pair from the main statistical comparison. Procedural checklists and regular team briefings will be used to minimize the risk of recurrence.

Statistical Analysis Plan Baseline demographic and clinical characteristics of enrolled patients will be summarized using descriptive statistics.

Because each patient contributes two DS, the statistical unit of analysis will be the individual wound, with paired observations within the same patient.

Comparisons between treatment modalities will be performed using paired statistical tests, selected according to the distribution and type of variables:

• parametric tests for normally distributed continuous variables
• non-parametric paired tests for non-normal distributions
• categorical data analysis where appropriate

The time to complete wound healing will be analyzed using survival analysis techniques, including:

• Kaplan-Meier survival curves
• log-rank test for comparison between treatment conditions Results will be reported using point estimates and 95% confidence intervals. The level of statistical significance will be set at p < 0.05. The planned sample size of 25 participants is considered adequate for this exploratory clinical investigation and allows paired comparisons of DS within subjects while ensuring feasibility within a single specialized burn center.

Handling of Missing Data Missing data may arise from incomplete assessments, missed follow-up visits, or documentation errors. When missing data occur, the circumstances will be documented in the CRF. Whenever possible, attempts will be made to retrieve missing information through review of medical records or contact with the patient.

Data that remain unavailable will be treated as missing values in the statistical analysis, and sensitivity analyses may be performed when appropriate to evaluate their potential impact on study results.

Inclusion criteria

• Patients with intermediate-deep burns with Total Body Surface Area (TBSA) > 10% requiring surgical treatment with escharectomy, presenting at least two Donor Site.
• Patients over 18 years of age;
• Patients who have signed the informed Consent Form (ICF) and understood the purpose of the study, or, if unable to give consent personally due to their condition, their legal guardian.

Exclusion criteria

• Intermediate-deep burns TBSA < 10% or superficial burns;
• Patients under the age of 18;
• Patients who are participating in other clinical trials with drugs or medical devices;
• Patients with neoplasms or other conditions requiring the use of cytostatic or immunosuppressive drugs;
• Patients with conditions that induce skin photosensitivity;
• Pregnant or breastfeeding women;
• Patients or relatives who are unable to understand the purposes of the trial;