Laser‐assisted drug delivery of synthetic alpha melanocyte stimulating hormone and L‐tyrosine leads to increased pigmentation area and expression of melanogenesis genes in a porcine hypertrophic scar model

Abstract

Objectives: One symptom of hypertrophic scar (HTS) that can develop after burn injury is dyschromia with hyper-and hypopigmentation. There are limited treatments for these conditions. Previously, we showed there is no expression of alpha melanocyte stimulating hormone (α-MSH) in hypopigmented scars, and if these melanocytes are treated with synthetic α-MSH in vitro, they respond by repigmenting. The current study tested the same hypothesis in the in vivo environment using laser-assisted drug delivery (LADD). Methods: HTSs were created in red Duroc pigs. At Day 77 (pre), they were treated with CO 2 fractional ablative laser (FLSR). Synthetic α-MSH was delivered as a topical solution dissolved in L-tyrosine (n = 6, treated). Control scars received LADD of L-tyrosine only (n = 2, control). Scars were treated and examined weekly through Week 4. Digital images and punch biopsies of hyper, hypo-, and normally pigmented scar and skin were collected. Digital pictures were analyzed with ImageJ by tracing the area of hyperpigmentation. Epidermal sheets were obtained from punch biopsies through dispase separation and RNA was isolated. qRT-PCR was run for melanogenesis-related genes: tyrosinase (TYR), tyrosinase-related protein-1 (TYRP1), and dopachrome tautomerase (DCT). Two-way ANOVA with multiple comparisons and Dunnett's correction compared the groups. Results: The areas of hyperpigmentation were variable before treatment. Therefore, data is represented as fold-change where each scar was normalized to its own pre value. Within the LADD of NDP α-MSH + L-tyrosine group, hyperpigmented areas gradually increased each week, reaching 1.3-fold over pre by Week 4. At each timepoint, area of hyperpigmentation was greater in the treated versus the control (1.04 ± 0.05 vs. 0.89 ± 0.08, 1.21 ± 0.07 vs. 0.98 ± 0.24, 1.21 ± 0.08 vs. 1.04 ± 0.11, 1.28 ± 0.11 vs. 0.94 ± 0.25; fold-change from pre-). Within the treatment group, pretreatment, levels of TYR were decreased −17.76 ± 4.52 below the level of normal skin in hypopigmented scars. After 1 treatment, potentially due to laser fractionation, the levels decreased to −43.49 ± 5.52. After 2, 3, and 4 treatments, there was ever increasing levels of TYR to almost the level of normally pigmented skin Week 4]). This pattern was also observed for TYRP1 (pre = −12.

Comparison of photodamage in non-pigmented and pigmented human skin equivalents exposed to repeated ultraviolet radiation to investigate the role of melanocytes in skin photoprotection

“…Individual typological angle (ITA) and melanin index (MI) measurements were obtained using a colourimeter, the SkinColorCatch (Delfin Technologies, Surrey, United Kingdom). The SkinColorCatch is a clinical instrument and colourimeter that is extensively used to determine facets of skin tone reliably in both in vitro ( 56 ) and in vivo settings ( 59–62 ). The readings were repeated three times in different surface areas to get an average value of the parameter.…”

Treatment of hypopigmented burn hypertrophic scars with short‐term topical tacrolimus does not lead to repigmentation

“…No topical formulation has been attempted in patients as of yet, although in our lab, we have tested its effect in vitro with success 13 and in vivo with limited success. 19 The use of topical tacrolimus has been successful in leading to repigmentation in the treatment of patients with vitiligo and may potentially be repurposed for use in hypopigmented burn scars. Tacrolimus (FK506) is a nonsteroidal anti-inflammatory and immunosuppressive drug that was first used as a topical agent to treat atopic dermatitis 20 and is commonly used systemically to prevent rejection after organ transplantation.…”

Metabolic Syndrome and Adipokines Profile in Bipolar Depression

“…The S100B is a calcium-binding protein responsible for transcriptional regulation and DNA repair, cell differentiation, cell growth and migration, and programmed cell death [12]. The S100B is predominantly expressed by astrocytes [13], and also by other cell types: melanocytes [14], chondrocytes, adipocytes [15,16], skeletal muscle, and a few other cell types [17]. In their research, Fujiya et al [18] proposed that the S100B functions as an adipokine in the interaction between adipocytes and macrophages.…”