Effect of Artesunate Combined With Fractional CO₂ Laser on the Hypertrophic Scar in a Rabbit Model

Abstract

Background and ObjectivesHypertrophic scar (HS), a common complication in wound healing, is characterized by the disarrangement of collagen, fibers, and extracellular matrix. Artesunate (ART) can inhibit the abnormal formation of fibroblasts and collagens. Fractional CO2 laser (FCO2L) can facilitate tissue remodeling and the absorption of drugs into ablative microthermal columns in HS. So far, no research has investigated the efficacy of ART combined with an FCO2L in treating HS. To investigate the theoretical basis and clinical significance of this combination, we established a rabbit model of HS to observe the change in the expression of transforming growth factor β1 (TGF‐β1) and proliferating cell nuclear antigen (PCNA).Study Design/Materials and MethodsForty New Zealand white rabbits were randomly divided into four groups: control group, ART group, FCO2L group, and ART + FCO2L (combination) group. Four wounds were surgically established in the ear of each rabbit and allowed to develop into HS. ART (20 μL/cm2) was injected in ART and combination groups, and FCO2L (combo mode, deep energy:10m J, super energy: 50 mJ) in FCO2L and combination groups on the 28th day after HS occurred. Three rounds of treatment were applied (once every 14 days). HS samples were measured by hematoxylin and eosin staining, Van Gieson staining, immunohistochemistry, and Western blot analysis on the 70th day.ResultsThe morphological and histopathological changes in HS were significant. HSs were smoother and smaller and the collagen fibers were thinner and less disordered in the combination group than those in ART and FCO2L groups. Meanwhile, the hypertrophic index (HI), fiber density (NA), and collagen fiber content (AA) were lower in the combination group (1.54 ± 0.15, 3.30 ± 0.22, 30.37 ± 1.41%) than in the ART group (2.51 ± 0.22, 4.69 ± 0.16, 44.68 ± 2.30%) and FCO2L group (1.99 ± 0.14, 4.13 ± 0.12, 37.74 ± 1.38%) (P < 0.01). Additionally, the expressions of TGF‐β1 and PCNA protein were suppressed in the ART group (0.30 ± 0.03, 0.25 ± 0.03) and FCO2L group (0.35 ± 0.03, 0.32 ± 0.05), and the suppression was more significant in the combination group(0.07 ± 0.02, 0.07 ± 0.02) (P < 0.01).ConclusionsThe combination of ART and FCO2L can effectively reduce HS in the rabbit model. This is the first report about this combination in the treatment of HS. A novel treatment is expected to be based on our findings. Lasers Surg. Med. © 2021 Wiley Periodicals LLC

Global research status of pathological scar reported over the period 2001–2021: A 20‐year bibliometric analysis

“…Among them, the animal scar model is one of the important methods to study pathological scar at present. The commonly used animal scar models include traditional animal scar models, such as the rodent model, rabbit ear model, and porcine model; however, none of these animal scar models can perfectly simulate the pathological scar formation and healing process of humans 37,38 . The rapid development of new technologies such as in vitro transplantation technology, transgenic technology, and tissue engineering technology also provides new ideas and strong support for the construction of scar model 39 .…”

“…The commonly used animal scar models include traditional animal scar models, such as the rodent model, rabbit ear model, and porcine model; however, none of these animal scar models can perfectly simulate the pathological scar formation and healing process of humans. 37 , 38 The rapid development of new technologies such as in vitro transplantation technology, transgenic technology, and tissue engineering technology also provides new ideas and strong support for the construction of scar model. 39 Organs‐on‐chips, which have been widely used in organ and disease models, are highly likely to be used to construct scar models in vitro in future.…”

Effectiveness and safety of fractional micro-plasma radio-frequency treatment combined with ablative fractional carbon dioxide laser treatment for hypertrophic scar: a retrospective study

“…A further subgroup analysis was also performed which revealed that patients at the early stage could experience more significant improvement after the treatment of combined therapy. Ablative fractional CO 2 laser technology has been employed for many years; however, it is only in recent years that this technique has been applied to the treatment of hypertrophic scars (3,4,(13)(14)(15)(16)(17)(18)(19). Several case reports firstly reported the effectiveness of ablative fractional CO 2 laser treatment for hypertrophic scars (20,21), then Makboul et al enrolled 40 patients with hypertrophic scars and confirmed ablative fractional CO 2 laser treatment as a feasible management for hypertrophic scarring (22).…”

CO2 Laser for Esthetic Healing of Injuries and Surgical Wounds with Small Parenchymal Defects in Oral Soft Tissues

“…Recently, the effectiveness of CO 2 lasers (a fractional CO 2 laser, in particular) for the treatment of epithelial scars from trauma, surgical wounds and acne was reported in clinical studies using biopsy samples [5][6][7][8][9], in studies using a scar scale or a visual analog scale [10][11][12][13][14][15][16] and in basic studies using experimental animals [17][18][19][20][21][22][23][24].…”