It has been shown several times that a dexpanthenol-containing formulation in the follow-up of laser treatment leads to positive clinical effects. The underlying mechanisms are not yet fully understood. A recent study using 3D skin models empirically demonstrated that the clinical effects of pantothenic acid (calcium pantothenate) are mainly due to regulation of MMP-3.
Adequate skin care following laser treatment has a positive effect on the healing of superficial wounds caused by medical or cosmetic interventions. To explore how wound-healing-promoting agents contribute to improved and faster wound closure, scientists have developed 3D skin models and gene expression analyses (box). Dexpanthenol, which is enzymatically converted into calcium pantothenate (pantothenic acid) by biotransformation in the organism, has demonstrated wound healing-promoting and hydrating properties. “Calcium pantothenate promotes accelerated wound closure,” summarizes Dr. rer.nat. Sebastian Huth from the Department of Dermatology and Allergology at the University Hospital RWTH Aachen (D) summarized the clinical effects of this compound [1]. As recent data show, matrix metalloproteinase-3 (MMP-3), among others, is significantly involved in accelerating wound healing (overview 1). To find out more about this, Huth et al. conducted experiments on laser-induced wounds on a three-dimensional skin model, the results of which they presented at this year’s virtual annual meeting of the Arbeitsgemeinschaft dermatologische Forschung (ADF).
Dexpanthenol promotes rapid wound closure
To study wound healing in a physiological model, a three-dimensional wound healing model was used in whichCO2 lasers were used to induce reproducible, defined injuries to the epidermis and upper dermis [2]. Subsequent topical application of a 5% dexpanthenol-containing emulsion was found to result in better wound healing than controls treated with petrolatum. To assess whether the improved wound healing was associated with the active ingredient dexpanthenol, the skin models were cultured with and without the addition of pantothenate (20 μg/ml). It was observed that after three days, wound closure was more advanced in the presence of pantothenate. Five days after laser intervention, the wounds in the pantothenate condition were shown to be almost completely re-epithelialized, whereas lesions were still visible in the controls. The promotion of the wound healing process by dexpanthenol could also be objectified on a genetic level. In the laser-irradiated skin models cultured with pantothenate-containing medium, quantitative real time PCR demonstrated modulatory effects on individual genes relevant to wound healing. Among others, increased mRNA expression of MMP-3, IL1α, and keratin-associated protein 4-12 (KRTAP4-12) and decreased expression of antimicrobial peptide S100A7 were detectable in the pantothenate condition.
That post-treatment with emulsions containing dexpanthenol followingCO2 laser irradiation is associated with accelerated wound healing compared with petrolatum was also shown by Heise et al. 2019 show by documenting wound diameters at day 1 and 2 after laser treatment [3]. In addition, visual inspection on days 1, 2, and 5 after laser intervention revealed significantly more favorable cosmetic results as well as better re-epithelialization of dexpanthenol-treated wounds compared with posttreatment with petrolatum. In summary, this comparative study indicates that post-operative treatment after laser treatment with a dexpanthenol-containing formulation results in accelerated wound healing compared to petrolatum, with this being particularly evident in the early stages of wound healing.
MMP-3 stimulates wound healing
To find out more details about the role of MMP-3 and its regulation by calcium pantothenate in wound healing processes, Huth et al. Using fibroblasts and keratinocytes to develop 3-D skin models with an MMP-3 knockdown [1,9]. Fractional ablative Er:YAG laser was used to induce superficial injuries. Histologic analysis three days after laser treatments showed that wound closure was slower in skin models with experimentally induced MMP-3 loss compared with MMP-3-expressing controls. The latter showed complete wound closure five days after laser intervention, whereas MMP-3 knockdown cells continued to have lesions at this time. Using microarray expression analysis, upregulation of several cytokines and chemokines (e.g., IL36B, CXCL17, IL37, CXCL5) and antimicrobial peptides, among others, was detected in the skin models with an MMP-3 knockdown on day 3 after laser irradiation compared with the MMP-3-expressing controls. This reflects delayed wound healing and a reduction in epidermal keratinocyte proliferation in the absence of MMP-3. Overall, these study results highlight the key role of MMP-3 in wound healing processes.
Congress: Arbeitsgemeinschaft Dermatologische Forschung 2021
Literature:
- Huth S, et al: MMP-3 plays a major role in calcium pantothenate-promoted wound healing after fractional ablative laser treatment. Dr. rer.nat. Sebastian Huth, ADF, 04.03.2021.
- Marquardt Y, et al. : Characterization of a novel standardized human three-dimensional skin wound healing model using non-sequential fractional ultrapulsed CO2 laser treatments. Lasers in Surgery and Medicine, 2015; 47(3): 257-265.
- Heise R, et al: Accelerated wound healing with a dexpanthenol-containing ointment after fractional ablative CO 2 laser resurfacing of photo-damaged skin in a randomized prospective clinical trial. Cutan Ocul Toxicol 2019; 38(3): 274-278.
- Marquardt Y, Baron JM, Huth S: Three-dimensional skin models serve as a basis for replication and research of various skin diseases and their treatment in vitro. Perspectives in Dermatology/2020 | Deutsches Ärzteblatt. DOI: 10.3238/PersDerma.2020.06.12.05
- RWTH Aachen University Hospital, Clinic for Dermatology and Allergology, www.ukaachen.de/kliniken-institute/klinik-fuer-dermatologie-und-allergologie-hautklinik/forschung/ag-baron
- Strobel S: The influence of matrix metalloproteinases and chlorhexidine on adhesive bonding. Swiss Dental Journal 2015; 2: 141-145
- Nguyen TT, Mobashery S, Chang M: Roles of matrix metalloproteinases in cutaneous wound healing. Wound Healing – New insights into ancient challnges: IntechOpen: London, UK, 2016. DOI: 10.5772/64611, www.intechopen.com
- Schmitt L, et al: Comprehensive molecular characterization of microneedling therapy in a human three-dimensional skin model. PLOS ONE, https://doi.org/10.1371/journal.pone.0204318 September 20, 2018.
- Huth S, et al: Upregulation of MMP-3 is a key mechanism in calcium pantothenate-mediated wound healing after fractional ablative laser treatment, P229, Abstract volume, ADF 2021.
DERMATOLOGIE PRAXIS 2021; 31(3): 44-45 (published 2.6.21, ahead of print).