Lung Surfactant Accelerates Skin Wound Healing: A Translational Study with a Randomized Clinical Phase I Study.
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
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
13 02 2020
13 02 2020
Historique:
received:
30
08
2019
accepted:
28
01
2020
entrez:
15
2
2020
pubmed:
15
2
2020
medline:
13
11
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 32054903
doi: 10.1038/s41598-020-59394-5
pii: 10.1038/s41598-020-59394-5
pmc: PMC7018835
doi:
Substances chimiques
Pulmonary Surfactant-Associated Proteins
0
Surface-Active Agents
0
Types de publication
Clinical Trial, Phase I
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2581Références
Harding, K. Innovation and wound healing. J. Wound Care 24(Suppl 4b), 7–13, https://doi.org/10.12968/jowc.2015.24.Sup4b.7 (2015).
doi: 10.12968/jowc.2015.24.Sup4b.7
pubmed: 25853643
Sen, C. K. et al. Human skin wounds: a major and snowballing threat to public health and the economy. Wound Repair. Regen. 17, 763–771, https://doi.org/10.1111/j.1524-475X.2009.00543.x (2009).
doi: 10.1111/j.1524-475X.2009.00543.x
pubmed: 19903300
pmcid: 2810192
Mirastschijski, U., Sander, J. T., Weyand, B. & Rennekampff, H. O. Rehabilitation of burn patients: An underestimated socio-economic burden. Burn. 39, 262–268, https://doi.org/10.1016/j.burns.2012.06.009 (2013).
doi: 10.1016/j.burns.2012.06.009
DGfW. S3-Leitlinie 091-001 “Lokaltherapie chronischer Wunden bei den Risiken CVI, PAVK und Diabetes mellitus”, 2012).
Mirastschijski, U. et al. The cost of post-burn scarring. Annals of burns and fire disasters 39, 976 (published online http://www.medbc.com/meditline/await_pub.htm , 2015).
Eming, S. A., Krieg, T. & Davidson, J. M. Inflammation in wound repair: molecular and cellular mechanisms. J. Investig. Dermatology 127, 514–525 (2007).
doi: 10.1038/sj.jid.5700701
Eming, S. A., Martin, P. & Tomic-Canic, M. Wound repair and regeneration: mechanisms, signaling, and translation. Sci. Transl. Med. 6, 265sr266, https://doi.org/10.1126/scitranslmed.3009337 (2014).
doi: 10.1126/scitranslmed.3009337
Olmeda, B., Martinez-Calle, M. & Perez-Gil, J. Pulmonary surfactant metabolism in the alveolar airspace: Biogenesis, extracellular conversions, recycling. Ann. Anatomy = Anatomischer Anzeiger: Off. Organ. Anatomische Ges. 209, 78–92, https://doi.org/10.1016/j.aanat.2016.09.008 (2017).
doi: 10.1016/j.aanat.2016.09.008
Knudsen, L. & Ochs, M. The micromechanics of lung alveoli: structure and function of surfactant and tissue components. Histochem. Cell. Biol. 150, 661–676, https://doi.org/10.1007/s00418-018-1747-9 (2018).
doi: 10.1007/s00418-018-1747-9
pubmed: 30390118
pmcid: 6267411
Bernhard, W. Lung surfactant: Function and composition in the context of development and respiratory physiology. Ann. Anatomy = Anatomischer Anzeiger: Off. Organ. Anatomische Ges. 208, 146–150, https://doi.org/10.1016/j.aanat.2016.08.003 (2016).
doi: 10.1016/j.aanat.2016.08.003
Wright, J. R. Immunoregulatory functions of surfactant proteins. Nat. Reviews. Immunology 5, 58–68, https://doi.org/10.1038/nri1528 (2005).
doi: 10.1038/nri1528
pubmed: 15630429
Halliday, H. L. Surfactants: past, present and future. J. Perinatol. 28(Suppl 1), S47–56 (2008).
doi: 10.1038/jp.2008.50
Akei, H. et al. Surface tension influences cell shape and phagocytosis in alveolar macrophages. Am. J. Physiol. Lung Cell Mol. Physiol 291, L572–579 (2006).
doi: 10.1152/ajplung.00060.2006
Kolomaznik, M., Nova, Z. & Calkovska, A. Pulmonary surfactant and bacterial lipopolysaccharide: the interaction and its functional consequences. Physiol. Res. 66, S147–S157 (2017).
doi: 10.33549/physiolres.933672
Yang, L. et al. Surfactant protein B propeptide contains a saposin-like protein domain with antimicrobial activity at low pH. J. Immunol. 184, 975–983, https://doi.org/10.4049/jimmunol.0900650 (2010).
doi: 10.4049/jimmunol.0900650
pubmed: 20007532
Bernhard, W. et al. Commercial versus native surfactants. Surface activity, molecular components, and the effect of calcium. Am. J. Respiratory Crit. Care Med. 162, 1524–1533, https://doi.org/10.1164/ajrccm.162.4.9908104 (2000).
doi: 10.1164/ajrccm.162.4.9908104
Kuronuma, K. et al. Anionic pulmonary surfactant phospholipids inhibit inflammatory responses from alveolar macrophages and U937 cells by binding the lipopolysaccharide-interacting proteins CD14 and MD-2. J. Biol. Chem. 284, 25488–25500, https://doi.org/10.1074/jbc.M109.040832 (2009).
doi: 10.1074/jbc.M109.040832
pubmed: 19584052
pmcid: 2757950
Tonks, A. et al. Surfactant phospholipid DPPC downregulates monocyte respiratory burst via modulation of PKC. Am. J. Physiol. Lung Cell Mol. Physiol 288, L1070–1080, https://doi.org/10.1152/ajplung.00386.2004 (2005).
doi: 10.1152/ajplung.00386.2004
pubmed: 15681395
Raychaudhuri, B. et al. Surfactant blocks lipopolysaccharide signaling by inhibiting both mitogen-activated protein and IkappaB kinases in human alveolar macrophages. Am. J. Respir. Cell Mol. Biol. 30, 228–232, https://doi.org/10.1165/rcmb.2003-0263OC (2004).
doi: 10.1165/rcmb.2003-0263OC
pubmed: 12920056
Volk, S. W. & Bohling, M. W. Comparative wound healing–are the small animal veterinarian’s clinical patients an improved translational model for human wound healing research? Wound Repair. Regen. 21, 372–381, https://doi.org/10.1111/wrr.12049 (2013).
doi: 10.1111/wrr.12049
pubmed: 23627643
Chen, L., Mirza, R., Kwon, Y., DiPietro, L. A. & Koh, T. J. The murine excisional wound model: Contraction revisited. Wound Repair. Regen. 23, 874–877, https://doi.org/10.1111/wrr.12338 (2015).
doi: 10.1111/wrr.12338
pubmed: 26136050
pmcid: 5094847
Willenborg, S. & Eming, S. A. Macrophages - sensors and effectors coordinating skin damage and repair. J. der Deutschen Dermatologischen Gesellschaft = Journal Ger. Soc. Dermatology: JDDG 12(214-221), 214–223, https://doi.org/10.1111/ddg.12290 (2014).
doi: 10.1111/ddg.12290
Mirastschijski, U. et al. Novel specific human and mouse stromelysin-1 (MMP-3) and stromelysin-2 (MMP-10) antibodies for biochemical and immunohistochemical analyses. Wound Repair Regen, https://doi.org/10.1111/wrr.12704 (2019).
doi: 10.1111/wrr.12704
Agren, M. S., Mirastschijski, U., Karlsmark, T. & Saarialho-Kere, U. K. Topical synthetic inhibitor of matrix metalloproteinases delays epidermal regeneration of human wounds. Exp. Dermatol. 10, 337–348 (2001).
doi: 10.1034/j.1600-0625.2001.100506.x
Moher, D. et al. CONSORT 2010 Explanation and Elaboration: Updated guidelines for reporting parallel group randomised trials. J. Clin. Epidemiol. 63, e1–37, https://doi.org/10.1016/j.jclinepi.2010.03.004 (2010).
doi: 10.1016/j.jclinepi.2010.03.004
pubmed: 20346624
Ashcroft, G. S. & Ashworth, J. J. Potential role of estrogens in wound healing. Am. J. Clin. Dermatol. 4, 737–743, https://doi.org/10.2165/00128071-200304110-00002 (2003).
doi: 10.2165/00128071-200304110-00002
pubmed: 14572296
Curstedt, T. Surfactant protein C: basics to bedside. J Perinatol 25 Suppl 2, S36–38; discussion S39, https://doi.org/10.1038/sj.jp.7211318 (2005).
doi: 10.1038/sj.jp.7211318
Curstedt, T. & Johansson, J. New synthetic surfactant - how and when? Biol. Neonate 89, 336–339, https://doi.org/10.1159/000092871 (2006).
doi: 10.1159/000092871
pubmed: 16770074
Numata, M., Kandasamy, P. & Voelker, D. R. Anionic pulmonary surfactant lipid regulation of innate immunity. Expert. Rev. Respir. Med. 6, 243–246, https://doi.org/10.1586/ers.12.21 (2012).
doi: 10.1586/ers.12.21
pubmed: 22788936
pmcid: 4444359
Seeds, M. C. et al. Secretory phospholipase A2-mediated depletion of phosphatidylglycerol in early acute respiratory distress syndrome. Am. J. Med. Sci. 343, 446–451, https://doi.org/10.1097/MAJ.0b013e318239c96c (2012).
doi: 10.1097/MAJ.0b013e318239c96c
pubmed: 22173044
pmcid: 3307942
Ikegami, M., Whitsett, J. A., Martis, P. C. & Weaver, T. E. Reversibility of lung inflammation caused by SP-B deficiency. Am. J. Physiol. Lung Cell Mol. Physiol 289, L962–970, https://doi.org/10.1152/ajplung.00214.2005 (2005).
doi: 10.1152/ajplung.00214.2005
pubmed: 16024721
Mao, P. et al. Human alveolar epithelial type II cells in primary culture. Physiol Rep 3, https://doi.org/10.14814/phy2.12288 (2015).
doi: 10.14814/phy2.12288
Lemke, A. et al. Human amniotic membrane as newly identified source of amniotic fluid pulmonary surfactant. Sci. Rep. 7, 6406, https://doi.org/10.1038/s41598-017-06402-w (2017).
doi: 10.1038/s41598-017-06402-w
pubmed: 28743969
pmcid: 5527005
Mo, Y. K. et al. Surfactant protein expression in human skin: evidence and implications. J. Investig. Dermatology 127, 381–386, https://doi.org/10.1038/sj.jid.5700561 (2007).
doi: 10.1038/sj.jid.5700561
Madsen, J. et al. Localization of lung surfactant protein D on mucosal surfaces in human tissues. J. Immunol. 164, 5866–5870 (2000).
doi: 10.4049/jimmunol.164.11.5866
Freeman, B. A., Panus, P. C., Matalon, S., Buckley, B. J. & Baker, R. R. Oxidant injury to the alveolar epithelium: biochemical and pharmacologic studies. Res Rep Health Eff Inst, 1–30; discussion 31–39 (1993).
Rugonyi, S., Biswas, S. C. & Hall, S. B. The biophysical function of pulmonary surfactant. Respiratory Physiol. Neurobiol. 163, 244–255, https://doi.org/10.1016/j.resp.2008.05.018 (2008).
doi: 10.1016/j.resp.2008.05.018
Bersani, I., Kunzmann, S. & Speer, C. P. Immunomodulatory properties of surfactant preparations. Expert. Rev. Anti Infect. Ther. 11, 99–110, https://doi.org/10.1586/eri.12.156 (2013).
doi: 10.1586/eri.12.156
pubmed: 23428105
Schyns, J., Bureau, F. & Marichal, T. Lung Interstitial Macrophages: Past, Present, and Future. J. Immunol. Res. 2018, 5160794, https://doi.org/10.1155/2018/5160794 (2018).
doi: 10.1155/2018/5160794
pubmed: 29854841
pmcid: 5952507
Sindrilaru, A. et al. An unrestrained proinflammatory M1 macrophage population induced by iron impairs wound healing in humans and mice. J. Clin. Investigation 121, 985–997, https://doi.org/10.1172/JCI44490 (2011).
doi: 10.1172/JCI44490
Mirza, R. & Koh, T. J. Dysregulation of monocyte/macrophage phenotype in wounds of diabetic mice. Cytokine 56, 256–264, https://doi.org/10.1016/j.cyto.2011.06.016 (2011).
doi: 10.1016/j.cyto.2011.06.016
pubmed: 21803601
Schultze, J. L., Schmieder, A. & Goerdt, S. Macrophage activation in human diseases. Semin. Immunology 27, 249–256, https://doi.org/10.1016/j.smim.2015.07.003 (2015).
doi: 10.1016/j.smim.2015.07.003
Dehghani, M., Azarpira, N., Mohammad Karimi, V., Mossayebi, H. & Esfandiari, E. Grafting with Cryopreserved Amniotic Membrane versus Conservative Wound Care in Treatment of Pressure Ulcers: A Randomized Clinical Trial. Bull. Emerg. Trauma. 5, 249–258, https://doi.org/10.18869/acadpub.beat.5.4.452. (2017).
doi: 10.18869/acadpub.beat.5.4.452.
pubmed: 29177171
pmcid: 5694597
Tenenhaus, M. The Use of Dehydrated Human Amnion/Chorion Membranes in the Treatment of Burns and Complex Wounds: Current and Future Applications. Ann. Plast. Surg. 78, S11–S13, https://doi.org/10.1097/SAP.0000000000000983 (2017).
doi: 10.1097/SAP.0000000000000983
pubmed: 28079550
Glat, P. M. The Evolution of Burn Injury Management: Using Dehydrated Human Amnion/Chorion Membrane Allografts in Clinical Practice. Ann. Plast. Surg. 78, S1, https://doi.org/10.1097/SAP.0000000000000982 (2017).
doi: 10.1097/SAP.0000000000000982
pubmed: 28079547
Mohammadi, A. A., Eskandari, S., Johari, H. G. & Rajabnejad, A. Using Amniotic Membrane as a Novel Method to Reduce Post-burn Hypertrophic Scar Formation: A Prospective Follow-up Study. J. Cutan. Aesthet. Surg. 10, 13–17, https://doi.org/10.4103/JCAS.JCAS_109_16 (2017).
doi: 10.4103/JCAS.JCAS_109_16
pubmed: 28529415
pmcid: 5418975
Zhao, B. et al. Exosomes derived from human amniotic epithelial cells accelerate wound healing and inhibit scar formation. J. Mol. Histol. 48, 121–132, https://doi.org/10.1007/s10735-017-9711-x (2017).
doi: 10.1007/s10735-017-9711-x
pubmed: 28229263
Tate, S., Price, A. & Harding, K. Dressings for venous leg ulcers. BMJ 361, k1604, https://doi.org/10.1136/bmj.k1604 (2018).
doi: 10.1136/bmj.k1604
pubmed: 29720376
Mullins, R. J., Richards, C. & Walker, T. Allergic reactions to oral, surgical and topical bovine collagen. Anaphylactic Risk Surgeons. Aust. N. Z. J. Ophthalmol. 24, 257–260, https://doi.org/10.1111/j.1442-9071.1996.tb01589.x (1996).
doi: 10.1111/j.1442-9071.1996.tb01589.x
pubmed: 8913129
Fitzgerald, R. H., Sabolinski, M. L. & Skornicki, M. Evaluation of Wound Closure Rates Using a Human Fibroblast-derived Dermal Substitute Versus a Fetal Bovine Collagen Dressing: A Retrospective Study. Wound Manag. Prev. 65, 26–34 (2019).
doi: 10.25270/wmp.2019.9.2634
Garwood, C. S. et al. The Use of Bovine Collagen-glycosaminoglycan Matrix for Atypical Lower Extremity Ulcers. Wounds 28, 298–305 (2016).
pubmed: 27701125
Kolenik, S. A. 3rd, McGovern, T. W. & Leffell, D. J. Use of a lyophilized bovine collagen matrix in postoperative wound healing. Dermatol. Surg. 25, 303–307, https://doi.org/10.1046/j.1524-4725.1999.08230.x (1999).
doi: 10.1046/j.1524-4725.1999.08230.x
pubmed: 10417587
Falanga, V. et al. Rapid healing of venous ulcers and lack of clinical rejection with an allogeneic cultured human skin equivalent. Human Skin Equivalent Investigators Group. Arch. Dermatol. 134, 293–300 (1998).
doi: 10.1001/archderm.134.3.293
DiDomenico, L. A. et al. Aseptically Processed Placental Membrane Improves Healing of Diabetic Foot Ulcerations: Prospective, Randomized Clinical Trial. Plastic Reconstructive Surgery. Glob. Open. 4, e1095, https://doi.org/10.1097/GOX.0000000000001095 (2016).
doi: 10.1097/GOX.0000000000001095
Lo, V., Lara-Corrales, I., Stuparich, A. & Pope, E. Amniotic membrane grafting in patients with epidermolysis bullosa with chronic wounds. J. Am. Acad. Dermatol. 62, 1038–1044, https://doi.org/10.1016/j.jaad.2009.02.048 (2010).
doi: 10.1016/j.jaad.2009.02.048
pubmed: 20466177
Johnson, E. L., Tassis, E. K., Michael, G. M. & Whittinghill, S. G. Viable placental allograft as a biological dressing in the clinical management of full-thickness thermal occupational burns: Two case reports. Med. 96, e9045, https://doi.org/10.1097/MD.0000000000009045 (2017).
doi: 10.1097/MD.0000000000009045
Kuntz, G., Wauer, R. R., Bernhard, W. & Pynn, C. J. Vol. 1 1–48 (Lyomark Pharma GmbH, Oberhaching, Germany, 2008).
Benz-Bohm, G. Kinderradiologie. 2nd edn., (Thieme, 2005).
Otte, A. et al. A tumor-derived population (SCCOHT-1) as cellular model for a small cell ovarian carcinoma of the hypercalcemic type. Int. J. Oncol. 41, 765–775, https://doi.org/10.3892/ijo.2012.1468 (2012).
doi: 10.3892/ijo.2012.1468
pubmed: 22581215
Repnik, U., Knezevic, M. & Jeras, M. Simple and cost-effective isolation of monocytes from buffy coats. J. Immunol. Methods 278, 283–292 (2003).
doi: 10.1016/S0022-1759(03)00231-X
Rehders, M. et al. Effects of lunar and mars dust simulants on HaCat keratinocytes and CHO-K1 fibroblasts. Adv. Space Res. 47, 1200–1213 (2011).
doi: 10.1016/j.asr.2010.11.033
Schindelin, J. et al. Fiji: an open-source platform for biological-image analysis. Nat. Methods 9, 676–682, https://doi.org/10.1038/nmeth.2019 (2012).
doi: 10.1038/nmeth.2019
Ascione, F. et al. Comparison between fibroblast wound healing and cell random migration assays in vitro. Exp. Cell Res. 347, 123–132, https://doi.org/10.1016/j.yexcr.2016.07.015 (2016).
doi: 10.1016/j.yexcr.2016.07.015
pubmed: 27475838
Rianna, C. & Radmacher, M. Influence of microenvironment topography and stiffness on the mechanics and motility of normal and cancer renal cells. Nanoscale 9, 11222–11230, https://doi.org/10.1039/c7nr02940c (2017).
doi: 10.1039/c7nr02940c
pubmed: 28752168
Tomasek, J. J. & Akiyama, S. K. Fibroblast-mediated collagen gel contraction does not require fibronectin-alpha 5 beta 1 integrin interaction. Anat. Rec. 234, 153–160, https://doi.org/10.1002/ar.1092340202 (1992).
doi: 10.1002/ar.1092340202
pubmed: 1416102
Mirastschijski, U., Haaksma, C. J., Tomasek, J. J. & Agren, M. S. Matrix metalloproteinase inhibitor GM 6001 attenuates keratinocyte migration, contraction and myofibroblast formation in skin wounds. Exp. Cell Res. 299, 465–475, https://doi.org/10.1016/j.yexcr.2004.06.007 (2004).
doi: 10.1016/j.yexcr.2004.06.007
pubmed: 15350544
Mirastschijski, U. et al. Ectopic localization of matrix metalloproteinase-9 in chronic cutaneous wounds. Hum. Pathol. 33, 355–364, https://doi.org/10.1053/hupa.2002.32221 (2002).
doi: 10.1053/hupa.2002.32221
pubmed: 11979378
Mirastschijski, U., Impola, U., Karsdal, M. A., Saarialho-Kere, U. & Agren, M. S. Matrix metalloproteinase inhibitor BB-3103 unlike the serine proteinase inhibitor aprotinin abrogates epidermal healing of human skin wounds ex vivo. J. Investig. Dermatology 118, 55–64, https://doi.org/10.1046/j.0022-202x.2001.01652.x (2002).
doi: 10.1046/j.0022-202x.2001.01652.x
Ardestani, A. et al. MST1 is a key regulator of beta cell apoptosis and dysfunction in diabetes. Nat. Med. 20, 385–397, https://doi.org/10.1038/nm.3482 (2014).
doi: 10.1038/nm.3482
pubmed: 24633305
pmcid: 3981675
He, W. et al. Ageing potentiates diet-induced glucose intolerance, beta-cell failure and tissue inflammation through TLR4. Sci. Rep. 8, 2767, https://doi.org/10.1038/s41598-018-20909-w (2018).
doi: 10.1038/s41598-018-20909-w
pubmed: 29426925
pmcid: 5807311
Aust, M. C. et al. Percutaneous collagen induction-Regeneration in place of cicatrisation? J. Plast. Reconstr. Aesthet. Surg. 64, 97–107, https://doi.org/10.1016/j.bjps.2010.03.038 (2010).
doi: 10.1016/j.bjps.2010.03.038
pubmed: 20413357
Stahl, F. et al. Transcriptome analysis. Adv. Biochem. Eng. Biotechnol. 127, 1–25, https://doi.org/10.1007/10_2011_102 (2012).
doi: 10.1007/10_2011_102
pubmed: 21952979
Schmidt, S. et al. Transcriptome-based identification of antioxidative gene expression after fish oil supplementation in normo- and dyslipidemic men. Nutr. Metab. 9, 45, https://doi.org/10.1186/1743-7075-9-45 (2012).
doi: 10.1186/1743-7075-9-45
Schmidt, S. et al. Different gene expression profiles in normo- and dyslipidemic men after fish oil supplementation: results from a randomized controlled trial. Lipids Health Dis. 11, 105, https://doi.org/10.1186/1476-511X-11-105 (2012).
doi: 10.1186/1476-511X-11-105
pubmed: 22929118
pmcid: 3484010
von der Haar, M., Lindner, P., Scheper, T. & Stahl, F. Array Analysis Manager—An automated DNA microarray analysis tool simplifying microarray data filtering, bias recognition, normalization, and expression analysis. Engineering in Life Sciences, https://doi.org/10.1002/elsc.201700046 (2017).
doi: 10.1002/elsc.201700046
von der Haar, M. et al. The Impact of Photobleaching on Microarray Analysis. Biol. 4, 556–572, https://doi.org/10.3390/biology4030556 (2015).
doi: 10.3390/biology4030556
von der Haar, M. et al. Optimization of Cyanine Dye Stability and Analysis of FRET Interaction on DNA Microarrays. Biology (Basel) 5, https://doi.org/10.3390/biology5040047 (2016).
doi: 10.3390/biology5040047
Eisen, M. B., Spellman, P. T., Brown, P. O. & Botstein, D. Cluster analysis and display of genome-wide expression patterns. Proc. Natl Acad. Sci. USA 95, 14863–14868 (1998).
doi: 10.1073/pnas.95.25.14863
Astner, S. et al. Non-invasive evaluation of the kinetics of allergic and irritant contact dermatitis. J. Investig. Dermatology 124, 351–359, https://doi.org/10.1111/j.0022-202X.2004.23605.x (2005).
doi: 10.1111/j.0022-202X.2004.23605.x
Mirastschijski, U. et al. Matrix metalloproteinase inhibition delays wound healing and blocks the latent transforming growth factor-beta1-promoted myofibroblast formation and function. Wound Repair. Regen. 18, 223–234, https://doi.org/10.1111/j.1524-475X.2010.00574.x (2010).
doi: 10.1111/j.1524-475X.2010.00574.x
pubmed: 20409148
pmcid: 2859473
Carlsson, A. M. Assessment of chronic pain. I. Aspects of the reliability and validity of the visual analogue scale. Pain. 16, 87–101 (1983).
doi: 10.1016/0304-3959(83)90088-X