Details
| Original language | English |
|---|---|
| Article number | 2581 |
| Journal | Scientific reports |
| Volume | 10 |
| Issue number | 1 |
| Publication status | Published - 13 Feb 2020 |
Abstract
Lung surfactants are used for reducing alveolar surface tension in preterm infants to ease breathing. Phospholipid films with surfactant proteins regulate the activity of alveolar macrophages and reduce inflammation. Aberrant skin wound healing is characterized by persistent inflammation. The aim of the study was to investigate if lung surfactant can promote wound healing. Preclinical wound models, e.g. cell scratch assays and full-thickness excisional wounds in mice, and a randomized, phase I clinical trial in healthy human volunteers using a suction blister model were used to study the effect of the commercially available bovine lung surfactant on skin wound repair. Lung surfactant increased migration of keratinocytes in a concentration-dependent manner with no effect on fibroblasts. Significantly reduced expression levels were found for pro-inflammatory and pro-fibrotic genes in murine wounds. Because of these beneficial effects in preclinical experiments, a clinical phase I study was initiated to monitor safety and tolerability of surfactant when applied topically onto human wounds and normal skin. No adverse effects were observed. Subepidermal wounds healed significantly faster with surfactant compared to control. Our study provides lung surfactant as a strong candidate for innovative treatment of chronic skin wounds and as additive for treatment of burn wounds to reduce inflammation and prevent excessive scarring.
Keywords
- Animals, Blister/drug therapy, Cell Proliferation/drug effects, Cicatrix/drug therapy, Female, Fibroblasts/drug effects, Humans, Inflammation/drug therapy, Keratinocytes/drug effects, Mice, Pulmonary Surfactant-Associated Proteins/pharmacology, Skin/drug effects, Surface-Active Agents, Wound Healing/drug effects
ASJC Scopus subject areas
Sustainable Development Goals
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In: Scientific reports, Vol. 10, No. 1, 2581, 13.02.2020.
Research output: Contribution to journal › Article › Research › peer review
}
TY - JOUR
T1 - Lung Surfactant Accelerates Skin Wound Healing
T2 - A Translational Study with a Randomized Clinical Phase I Study
AU - Mirastschijski, Ursula
AU - Schwab, Igor
AU - Coger, Vincent
AU - Zier, Ulrich
AU - Rianna, Carmela
AU - He, Wei
AU - Maedler, Kathrin
AU - Kelm, Sørge
AU - Radtke, Arlo
AU - Belge, Gazanfer
AU - Lindner, Patrick
AU - Stahl, Frank
AU - Scharpenberg, Martin
AU - Lasota, Lukas
AU - Timm, Jürgen
N1 - Funding information: We acknowledge Reinhild Schnabel, Angela Fülbier, Regina Bolte, Petra Berger and Katrischa Hennekens for excellent technical assistance. We are grateful to K. Junker (Department of Pathology), and C. Lorenz (Department of Pediatric Surgery, both Klinikum Bremen-Mitte, Bremen) for their support and cooperation in this study, to M. Klouche (Bremen Center for Laboratory Medicine GmbH) for performing the blood sample analyses and to Melanie Braun (Blutspendedienst Hamburg) for providing the buffy coats from anonymous funded by the European Research Council under the European Communihealthy donors. We thank Lyomark Pharma GmbH for donating Alveofact®ty’s Seventh Framework Programmefor the clinical study. This work was (FP7/2007-2013; n° 243195) and under the European Union’s Horizon 2020 research and innovation programme (No. 693017).
PY - 2020/2/13
Y1 - 2020/2/13
N2 - Lung surfactants are used for reducing alveolar surface tension in preterm infants to ease breathing. Phospholipid films with surfactant proteins regulate the activity of alveolar macrophages and reduce inflammation. Aberrant skin wound healing is characterized by persistent inflammation. The aim of the study was to investigate if lung surfactant can promote wound healing. Preclinical wound models, e.g. cell scratch assays and full-thickness excisional wounds in mice, and a randomized, phase I clinical trial in healthy human volunteers using a suction blister model were used to study the effect of the commercially available bovine lung surfactant on skin wound repair. Lung surfactant increased migration of keratinocytes in a concentration-dependent manner with no effect on fibroblasts. Significantly reduced expression levels were found for pro-inflammatory and pro-fibrotic genes in murine wounds. Because of these beneficial effects in preclinical experiments, a clinical phase I study was initiated to monitor safety and tolerability of surfactant when applied topically onto human wounds and normal skin. No adverse effects were observed. Subepidermal wounds healed significantly faster with surfactant compared to control. Our study provides lung surfactant as a strong candidate for innovative treatment of chronic skin wounds and as additive for treatment of burn wounds to reduce inflammation and prevent excessive scarring.
AB - Lung surfactants are used for reducing alveolar surface tension in preterm infants to ease breathing. Phospholipid films with surfactant proteins regulate the activity of alveolar macrophages and reduce inflammation. Aberrant skin wound healing is characterized by persistent inflammation. The aim of the study was to investigate if lung surfactant can promote wound healing. Preclinical wound models, e.g. cell scratch assays and full-thickness excisional wounds in mice, and a randomized, phase I clinical trial in healthy human volunteers using a suction blister model were used to study the effect of the commercially available bovine lung surfactant on skin wound repair. Lung surfactant increased migration of keratinocytes in a concentration-dependent manner with no effect on fibroblasts. Significantly reduced expression levels were found for pro-inflammatory and pro-fibrotic genes in murine wounds. Because of these beneficial effects in preclinical experiments, a clinical phase I study was initiated to monitor safety and tolerability of surfactant when applied topically onto human wounds and normal skin. No adverse effects were observed. Subepidermal wounds healed significantly faster with surfactant compared to control. Our study provides lung surfactant as a strong candidate for innovative treatment of chronic skin wounds and as additive for treatment of burn wounds to reduce inflammation and prevent excessive scarring.
KW - Animals
KW - Blister/drug therapy
KW - Cell Proliferation/drug effects
KW - Cicatrix/drug therapy
KW - Female
KW - Fibroblasts/drug effects
KW - Humans
KW - Inflammation/drug therapy
KW - Keratinocytes/drug effects
KW - Mice
KW - Pulmonary Surfactant-Associated Proteins/pharmacology
KW - Skin/drug effects
KW - Surface-Active Agents
KW - Wound Healing/drug effects
UR - http://www.scopus.com/inward/record.url?scp=85079338726&partnerID=8YFLogxK
U2 - 10.1038/s41598-020-59394-5
DO - 10.1038/s41598-020-59394-5
M3 - Article
C2 - 32054903
VL - 10
JO - Scientific reports
JF - Scientific reports
SN - 2045-2322
IS - 1
M1 - 2581
ER -