IR-808 loaded nanoethosomes for aggregation-enhanced synergistic transdermal photodynamic/photothermal treatment of hypertrophic scars.

Synergistic transdermal photodynamic therapy (PDT)/photothermal therapy (PTT) has emerged as a novel strategy for improving hypertrophic scar (HS) therapeutic outcomes. Herein, a near-infrared heptamethine cyanine dye, named IR-808, has been selected as the desirable photosensitizer owing to its PDT and PTT properties. Benefitting from the transdermal delivery ability of ethosomes (ESs), IR-808 loaded nanoethosomes (IR-808-ES) have been prepared as a novel nanophotosensitizer for the transdermal PDT/PTT of HSs. The special structure of IR-808 aggregate distribution in the ES lipid membrane enhances ROS generation and hyperthermia. The in vitro experiments indicate that the IR-808-ES enhances the PDT/PTT efficacy for inducing the HS fibroblast (HSF) apoptosis via the intrinsic mitochondrial pathway. Furthermore, the in vivo transdermal delivery studies reveal that the IR-808-ES efficiently delivers IR-808 into HSFs in the HS tissue. Systematic assessments in the rabbit ear HS models demonstrate that the enhanced PDT/PTT performance of the IR-808-ES has remarkable therapeutic effects on improving the HS appearance, promoting HSF apoptosis and remodeling collagen fibers. Therefore, the IR-808-ES integrates both the transdermal delivery ability and the aggregation-enhanced PDT/PTT effect, and these features endow the IR-808-ES with significant potential as a novel nanophotosensitizer for the transdermal phototherapy of HSs in the clinical field.

Efficacy and safety of a dual-scan protocol for carbon dioxide laser in the treatment of split-thickness skin graft contraction in a red Duroc pig model.

BACKGROUND: Fractional CO2 laser plays an important role in scar management post split-thickness skin graft by loosening the graft contracture and restoring the smoothness of the surface. However, the optimal treatment protocol remains unknown. This study applied a dual-scan protocol to achieve both releasing and ablation of contracted skin graft. We comprehensively describe this treatment method and compare the efficacy and safety between this dual-scan method and the conventional mono-scan mode. METHODS: A hypercontracted scar model after split-thickness skin grafting in red Duroc pigs was established. All scars meeting the inclusion criteria were randomly divided into four groups: high fluence-low density (HF-LD), low fluence-high density (LF-HD), combined group and control group. The energy per unit area was similar in the HF-LD and LF-HD groups. Two laser interventions were performed at a 6-week interval. The efficacy of the treatment was evaluated by objective measures of scar area, release rate, elasticity, thickness and flatness, while the safety was evaluated based on adverse reactions and melanin index. Collagen structure was observed histologically. The animals were followed up for a maximum of 126 days after modeling. RESULTS: A total of 28 contracted scars were included, 7 in each group. At 18 weeks postoperatively, the HF-LD and the combined groups showed significantly increased scar release rate (p = 0.000) and elasticity (p = 0.036) and decreased type I/III collagen ratio (p = 0.002) compared with the control and LF-HD groups. In terms of flatness, the combined group was significantly better than the HF-LD group for elevations <1 mm (p = 0.019). No significant skin side effects, pigmentation or scar thickness changes were observed at 18 weeks. CONCLUSIONS: Dual-scan protocol could achieve superficial ablation and deep release of contracted split-thickness skin graft in a single treatment, with similar contraction release and texture improvement compared to a single deep scan. Its main advantage is to restore a smoother scar appearance. Adequate laser penetration was necessary for the release of contracted scars.