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 -