Lessons Learned Evaluating Ablative Fractional CO2 Laser for Burn-Related Donor Site Scars

Abstract Hypertrophic scar (HTS) remains a comorbidity of burn injury, often requiring split thickness skin grafting (STSG) and resulting in symptomatic HTS at grafted sites and STSG donor sites (DS). Literature supports the use of ablative fractional CO2 laser (FLSR) to treat HTS, however many trials lack of control sites and tissue-level examinations. Given the widespread adoption of FLSR for HTS, delegation of non-treated scar sites for the sake of randomized controlled trial (RCT) is troubling for many clinicians. We trialed using STSG DS scars for randomization rather than withholding FLSR from HTS at grafted sites. Patients (n=20) were treated for DS scar with FLSR. DS scars were randomized and treated with either 6 FLSR treatments, follow-ups, and standard of care (SOC) or SOC only. Prior to treatment, DS skin and normal skin (NS) were evaluated for trans-epidermal water loss (TEWL), melanin index (MI), elasticity, and erythema. Serial biopsies were analyzed for epidermal thickness, rete ridge ratio (RRR), and papillary dermal cellularity. All sites, including a separate burn scar (BS) site, were evaluated using the patient and observer scar assessment scale (POSAS) -observer (-O), -patient (-P), Vancouver Scar Scale (VSS), and an institutional Scar Comparison Scale (SCS). Prior to treatment, the DS control (DS C), DS treated (DS T), and BS sites were hyperpigmented compared to normal skin. BS was less elastic than all other sites and had increased TEWL compared to normal skin. DS skin had increased cellularity, decreased rete ridge ratios, and increased epidermal thickness compared to NS. Clinician observers and patients perceived the BS site as more severe versus DS skin through the POSAS-O, POSAS-P, and VSS. Over time, DS C and DS T sites were not different in TEWL, elasticity, erythema, MI, cellularity, RRR, epidermal thickness, POSAS-O scores, POSAS-P scores, VSS scores, or SCS scores. Over time, burn scar did not change in TEWL, elasticity, erythema, MI, POSAS-O scores, POSAS-P scores, and VSS scores. Decreased SCS scores within the DS C, DS T, and BS sites indicated patient-perceived improvement in all scars throughout the study time course. NS and DS skin possess inherent physiological differences, though not to the degree of burn scars vs. NS. FLSR may not alter the rate of maturation and remodeling of DS skin compared to current SOC. While improvement in scar assessment was observed in laser-treated BS HTS, no specific control for these sites was analyzed. Due to differences in pathophysiology of HTS formation at grafted and donor sites, the STSG DS may not be an adequate substitute for BS HTS when designing RCTs to evaluate the effect of FLSR. Prior studies evaluating the use FLSR in burn-related HTS consist of low-powered clinical trials or case studies without control sites or tissue level examinations, prompting the design of a RCT in DS scars. However, this scar type may not be suitable for this study design. Future work should extend to extra-cellular matrix morphology and transcriptomics of donor site and burn scar healing to better understand the effects of laser treatment.