Skip to main content

Advertisement

Log in

Human as the Ultimate Wound Healing Model: Strategies for Studies Investigating the Dermal Lipidome

  • Wound Care and Healing (A Friedman, Section Editor)
  • Published:
Current Dermatology Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

The purpose of this review was to educate the reader of the multiple roles undertaken by the human epidermal lipidome and the experimental techniques of measuring them.

Recent Findings

Damage to skin elicits a wound healing process that is capped by the recreation of the lipid barrier. In addition to barrier function, lipids also undertake an active signaling role during wound healing. Achievement of these multiple functions necessitates a significant complexity and diversity in the lipidome resulting in a composition that is unique to the human skin. As such, any attempts to delineate the function of the lipidome during the wound healing process in humans need to be addressed via studies undertaken in humans.

Summary

The human cutaneous lipidome is unique and plays a functionally significant role in maintaining barrier and regulating wound healing. Modern mass spectrometry and Raman spectroscopy-based methods enable the investigation of epidermal lipidome with respect to those functions.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

Recently Published Papers of Particular Interest Have Been Highlighted as: • Of Importance

  1. Nicolaides N. Skin lipids: their biochemical uniqueness. Science. 1974;186:19–26.

    Article  CAS  PubMed  Google Scholar 

  2. Rogers J, Harding C, Mayo A, Banks J, Rawlings A. Stratum corneum lipids: the effect of ageing and the seasons. Arch Dermatol Res. 1996;288:765–70.

    Article  CAS  PubMed  Google Scholar 

  3. Muizzuddin N, Hellemans L, Van Overloop L, Corstjens H, Declercq L, Maes D. Structural and functional differences in barrier properties of African American, Caucasian and East Asian skin. J Dermatol Sci. 2010;59:123–8.

    Article  CAS  PubMed  Google Scholar 

  4. Pappas A, Fantasia J, Chen T. Age and ethnic variations in sebaceous lipids. Dermatoendocrinol. 2013;5:319–24. Demonstrates the variability of the skin surface lipidome among humans

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Lampe MA, Burlingame AL, Whitney J, Williams ML, Brown BE, Roitman E, Elias PM. Human stratum corneum lipids: characterization and regional variations. J Lipid Res. 1983;24:120–30.

    CAS  PubMed  Google Scholar 

  6. Tingstad JE, Wurster DE, Higuchi T. Investigation of human skin lipids II. J Am Pharm Assoc Sci Ed. 1958;47:192–3.

    Article  CAS  Google Scholar 

  7. Picardo M, Ottaviani M, Camera E, Mastrofrancesco A. Sebaceous gland lipids. Dermatoendocrinol. 2009;1:68–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Fischer CL, Drake DR, Dawson DV, Blanchette DR, Brogden KA, Wertz PW. Antibacterial activity of sphingoid bases and fatty acids against gram-positive and gram-negative bacteria. Antimicrob Agents Chemother. 2012;56:1157–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Drake DR, Brogden KA, Dawson DV, Wertz PW. Thematic review series: skin lipids. Antimicrobial lipids at the skin surface. J Lipid Res. 2008;49:4–11.

    Article  CAS  PubMed  Google Scholar 

  10. Cossette C, Patel P, Anumolu JR, Sivendran S, Lee GJ, Gravel S, Graham FD, Lesimple A, Mamer OA, Rokach J, Powell WS. Human neutrophils convert the sebum-derived polyunsaturated fatty acid sebaleic acid to a potent granulocyte chemoattractant. J Biol Chem. 2008;283:11234–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Smith KR, Thiboutot DM. Thematic review series: skin lipids. Sebaceous gland lipids: friend or foe? J Lipid Res. 2008;49:271–81.

    Article  CAS  PubMed  Google Scholar 

  12. Motta S, Monti M, Sesana S, Mellesi L, Ghidoni R, Caputo R. Abnormality of water barrier function in psoriasis: role of ceramide fractions. Arch Dermatol. 1994;130:452–6.

    Article  CAS  PubMed  Google Scholar 

  13. Hon KL, Leung AKC, Barankin B. Barrier repair therapy in atopic dermatitis: an overview. Am J Clin Dermatol. 2013;14:389–99.

    Article  PubMed  Google Scholar 

  14. Mizutani Y, Mitsutake S, Tsuji K, Kihara A, Igarashi Y. Ceramide biosynthesis in keratinocyte and its role in skin function. Biochimie. 2009;91:784–90.

    Article  CAS  PubMed  Google Scholar 

  15. Di Nardo A, Wertz P, Giannetti A, Seidenari S. Ceramide and cholesterol composition of the skin of patients with atopic dermatitis. Acta Derm Venereol. 1998;78:27–30.

    Article  CAS  PubMed  Google Scholar 

  16. Elias PM. Epidermal lipids, barrier function, and desquamation. J. Invest. Dermatol. 1983;80:44s–9s.

    Article  CAS  Google Scholar 

  17. Wijesinghe DS, Brentnall M, Mietla JA, Hoeferlin LA, Diegelmann RF, Boise LH, Chalfant CE. Ceramide kinase is required for a normal eicosanoid response and the subsequent orderly migration of fibroblasts. J Lipid Res. 2014;55:1298–309.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Nicolaou A. Eicosanoids in skin inflammation. Prostaglandins Leukot Essent Fat Acids PLEFA. 2013;88:131–8. Provides an excellent description of how eicosanoids are involved in the regulation of skin inflammation

    Article  CAS  Google Scholar 

  19. Hoeferlin LA, Huynh QK, Mietla JA, Sell SA, Tucker J, Chalfant CE, Wijesinghe DS. The lipid portion of activated platelet-rich plasma significantly contributes to its wound healing properties. Adv. Wound Care. 2015;4:100–9.

    Article  Google Scholar 

  20. Sun L, Xu L, Henry FA, Spiegel S, Nielsen TB. A new wound healing agent—sphingosylphosphorylcholine. J. Invest. Dermatol. 1996;106:232–7.

    Article  CAS  PubMed  Google Scholar 

  21. Xu K-P, Yin J, Yu F-SX. Lysophosphatidic acid promoting corneal epithelial wound healing by transactivation of epidermal growth factor receptor. Invest Ophthalmol Vis Sci. 2007;48:636–43.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Hellmann J, Tang Y, Spite M. Pro-resolving lipid mediators and diabetic wound healing. Curr Opin Endocrinol Diabetes Obes. 2012;19:104–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Ishikawa J, Narita H, Kondo N, Hotta M, Takagi Y, Masukawa Y, Kitahara T, Takema Y, Koyano S, Yamazaki S, Hatamochi A. Changes in the ceramide profile of atopic dermatitis patients. J. Invest. Dermatol. 2010;130:2511–4.

    Article  CAS  PubMed  Google Scholar 

  24. Yamamoto A, Serizawa S, Ito M, Sato Y. Stratum corneum lipid abnormalities in atopic dermatitis. Arch Dermatol Res. 1991;283:219–23.

    Article  CAS  PubMed  Google Scholar 

  25. Schäfer L, Kragballe K. Abnormalities in epidermal lipid metabolism in patients with atopic dermatitis. J. Invest. Dermatol. 1991;96:10–5.

    Article  PubMed  Google Scholar 

  26. Kleuser B, Japtok L. Sphingolipids and inflammatory diseases of the skin. Handb Exp Pharmacol. 2013;10.

  27. Higuchi K, Hara J, Okamoto R, Kawashima M, Imokawa G. The skin of atopic dermatitis patients contains a novel enzyme, glucosylceramide sphingomyelin deacylase, which cleaves the N-acyl linkage of sphingomyelin and glucosylceramide. Biochem J. 2000;350:747–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Motta S, Monti M, Sesana S, Caputo R, Carelli S, Ghidoni R. Ceramide composition of the psoriatic scale. Biochim Biophys Acta BBA-Mol Basis Dis. 1993;1182:147–51.

    Article  CAS  Google Scholar 

  29. Alessandrini F, Stachowitz S, Ring J, Behrendt H. The level of prosaposin is decreased in the skin of patients with psoriasis vulgaris. J. Invest. Dermatol. 2001;116:394–400.

    Article  CAS  PubMed  Google Scholar 

  30. Doering T, Holleran WM, Potratz A, Vielhaber G, Elias PM, Suzuki K, Sandhoff K. Sphingolipid activator proteins are required for epidermal permeability barrier formation. J Biol Chem. 1999;274:11038–45.

    Article  CAS  PubMed  Google Scholar 

  31. Grabowski GA. Gaucher disease and other storage disorders. ASH Educ Program Book. 2012;2012:13–8.

    Google Scholar 

  32. Holleran WM, Ginns EI, Menon GK, Grundmann JU, Fartasch M, McKinney CE, Elias PM, Sidransky E. Consequences of beta-glucocerebrosidase deficiency in epidermis. Ultrastructure and permeability barrier alterations in Gaucher disease. J Clin Invest. 1994;93:1756–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Castiel-Higounenc I, Chopart M, Ferraris C. Stratum corneum lipids: specificity, role, deficiencies and modulation. Ol Corps Gras Lipides. 2004;11:401–6.

    Article  CAS  Google Scholar 

  34. Mourelatos K, Eady EA, Cunliffe WJ, Clark SM, Cove JH. Temporal changes in sebum excretion and propionibacterial colonization in preadolescent children with and without acne. Br J Dermatol. 2007;156:22–31.

    Article  CAS  PubMed  Google Scholar 

  35. Harris HH, Downing DT, Stewart ME, Strauss JS. Sustainable rates of sebum secretion in acne patients and matched normal control subjects. J Am Acad Dermatol. 1983;8:200–3.

    Article  CAS  PubMed  Google Scholar 

  36. Piérard-Franchimont C, Piérard GE, Saint-Léger D, Lévêque JL, Kligman AM. Comparison of the kinetics of sebum secretion in young women with and without acne. Dermatologica. 1991;183:120–2.

    Article  PubMed  Google Scholar 

  37. Ottaviani M, Camera E, Picardo M, Ottaviani M, Camera E, Picardo M. Lipid mediators in acne, lipid mediators in acne. Mediat Inflamm Mediat Inflamm. 2010;2010:e858176.

    Google Scholar 

  38. Meckfessel MH, Brandt S. The structure, function, and importance of ceramides in skin and their use as therapeutic agents in skin-care products. J Am Acad Dermatol. 2014;71:177–84.

    Article  CAS  PubMed  Google Scholar 

  39. Rabasco Álvarez, A. M., González Rodríguez, M. L., and et al. [2000] Lipids in pharmaceutical and cosmetic preparations. [online] https://idus.us.es/xmlui/handle/11441/17554 [Accessed July 6, 2016]

  40. Clausen M-L, Slotved H-C, Krogfelt KA, Agner T. Tape stripping technique for stratum corneum protein analysis. Sci Rep. 2016;6:19918.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Hendrix SW, Miller KH, Youket TE, Adam R, O’Connor RJ, Morel JG, Tepper BE. Optimization of the skin multiple analyte profile bioanalytical method for determination of skin biomarkers from D-Squame tape samples. Skin Res Technol Off J Int Soc Bioeng Skin ISBS Int Soc Digit Imaging Skin ISDIS Int Soc Skin Imaging ISSI. 2007;13:330–42.

    CAS  Google Scholar 

  42. Widgerow AD, King K, Tocco-Tussardi I, Banyard DA, Chiang R, Awad A, Afzel H, Bhatnager S, Melkumyan S, Wirth G, Evans GRD. The burn wound exudate-an under-utilized resource. Burns J Int Soc Burn Inj. 2015;41:11–7.

    Article  Google Scholar 

  43. Danielsen PL, Jorgensen LN, Jørgensen B, Karlsmark T, Agren MS. Erythema persists longer than one year in split-thickness skin graft donor sites. Acta Derm Venereol. 2013;93:281–5.

    Article  PubMed  Google Scholar 

  44. Lawrence JC, Ameen H. Swabs and other sampling techniques. J Wound Care. 1998;7:232–3.

    CAS  PubMed  Google Scholar 

  45. Yang S, Kampp J. Common dermatologic procedures. Med Clin North Am. 2015;99:1305–21.

    Article  PubMed  Google Scholar 

  46. Nwomeh BC, Liang HX, Diegelmann RF, Cohen IK, Yager DR. Dynamics of the matrix metalloproteinases MMP-1 and MMP-8 in acute open human dermal wounds. Wound Repair Regen. 1998;6:127–34.

    Article  CAS  PubMed  Google Scholar 

  47. Efron, D. T., and Barbul, A. [2003] Subcutaneous Sponge Models in Wound Healing: Methods and Protocols [DiPietro, L. A. ed], pp. 83–93, Humana Press Inc., Totowa, New Jersey

  48. Alaish SM, Bettinger DA, Olutoye OO, Gould LJ, Yager DR, Davis A, Crossland MC, Diegelmann RF, Cohen I. Comparison of the polyvinyl alcohol [PVA] and ePTFE [Impra®] subcutaneous implants as models to evaluate wound healing potential in humans. Wound Repair Regen. 1995;3:292–8.

    Article  CAS  PubMed  Google Scholar 

  49. Jorgensen LN, Olsen L, Kallehave F, Karlsmark T, Diegelmann RF, Cohen IK, Gottrup F. The wound healing process in surgical patients evaluated by the ePTFE and the polyvinyl alcohol sponge: a comparison with special reference to the intra-patient variation. Wound Repair Regen. 1995;3:527–32.

    Article  CAS  PubMed  Google Scholar 

  50. Jorgensen LN, Madsen SM, Gottrup F. Implantable wound healing models and the determination of subcutaneous collagen deposition in expanded polytetrafluoroethylene implants. Methods Mol Med. 2003;78:263–73.

    PubMed  Google Scholar 

  51. Diegelmann RF, Lindblad WJ, Cohen IK. A subcutaneous implant for wound healing studies in humans. J Surg Res. 1986;40:229–37.

    Article  CAS  PubMed  Google Scholar 

  52. Oswal V, Belle A, Diegelmann R, Najarian K. Comput. Math Methods Med. 2013;2013:592790.

    Google Scholar 

  53. Boniforti L, Passi S, Caprilli F, Porro MN. Skin surface lipids. Identification and determination by thin-layer chromatography and gas-liquid chromatography. Clin Chim Acta. 1973;47:223–31.

    Article  CAS  PubMed  Google Scholar 

  54. Wertz PW, Schwartzendruber DC, Madison KC, Downing DT. Composition and morphology of epidermal cyst lipids. J. Invest. Dermatol. 1987;89:419–25.

    Article  CAS  PubMed  Google Scholar 

  55. Masukawa Y, Narita H, Sato H, Naoe A, Kondo N, Sugai Y, Oba T, Homma R, Ishikawa J, Takagi Y, Kitahara T. Comprehensive quantification of ceramide species in human stratum corneum. J Lipid Res. 2009;50:1708–19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Weerheim A, Ponec M. Determination of stratum corneum lipid profile by tape stripping in combination with high-performance thin-layer chromatography. Arch Dermatol Res. 2001;293:191–9.

    Article  CAS  PubMed  Google Scholar 

  57. Long SA, Wertz PW, Strauss JS, Downing DT. Human stratum corneum polar lipids and desquamation. Arch Dermatol Res. 277:284–7.

  58. Wertz PW, Miethke MC, Long SA, Strauss JS, Downing DT. The composition of the ceramides from human stratum corneum and from comedones. J Invest Dermatol. 1985;84:410–2.

    Article  CAS  PubMed  Google Scholar 

  59. Do UH, Pei PT, Minard RD. Separation of molecular species of ceramides as benzoyl andp-nitrobenzoyl derivatives by high performance liquid chromatography. Lipids. 1981;16:855–62.

    Article  CAS  Google Scholar 

  60. Masukawa Y, Tsujimura H, Imokawa G. A systematic method for the sensitive and specific determination of hair lipids in combination with chromatography. J Chromatogr B. 2005;823:131–42.

    Article  CAS  Google Scholar 

  61. Pons A, Timmerman P, Leroy Y, Zanetta J-P. Gas-chromatography/mass-spectrometry analysis of human skin constituents as heptafluorobutyrate derivatives with special reference to long-chain bases. J Lipid Res. 2002;43:794–804.

    CAS  PubMed  Google Scholar 

  62. Michael-Jubeli R, Bleton J, Baillet-Guffroy A. High-temperature gas chromatography-mass spectrometry for skin surface lipids profiling. J Lipid Res. 2011;52:143–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. van Smeden J, Hoppel L, van der Heijden R, Hankemeier T, Vreeken RJ, Bouwstra JA. LC/MS analysis of stratum corneum lipids: ceramide profiling and discovery. J Lipid Res. 2011;52:1211–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. van Smeden J, Boiten WA, Hankemeier T, Rissmann R, Bouwstra JA, Vreeken RJ. Combined LC/MS-platform for analysis of all major stratum corneum lipids, and the profiling of skin substitutes. Biochim Biophys Acta BBA-Mol Cell Biol Lipids. 2014;1841:70–9.

    Article  CAS  Google Scholar 

  65. Masukawa Y, Narita H, Shimizu E, Kondo N, Sugai Y, Oba T, Homma R, Ishikawa J, Takagi Y, Kitahara T, Takema Y, Kita K. Characterization of overall ceramide species in human stratum corneum. J Lipid Res. 2008;49:1466–76.

    Article  CAS  PubMed  Google Scholar 

  66. Kendall AC, Nicolaou A. Bioactive lipid mediators in skin inflammation and immunity. Prog Lipid Res. 2013;52:141–64.

    Article  CAS  PubMed  Google Scholar 

  67. Wijesinghe DS, Chalfant CE. Systems-level lipid analysis methodologies for qualitative and quantitative investigation of lipid signaling events during wound healing. Adv Wound Care. 2013;2:538–48. Provides detailed information with respect to tha application of mass spectrometry methods to study lipid changes during wound healing

    Article  Google Scholar 

  68. Dhall S, Wijesinghe DS, Karim ZA, Castro A, Vemana HP, Khasawneh FT, Chalfant CE, Martins-Green M. Arachidonic acid-derived signaling lipids and functions in impaired healing. Wound Repair Regen Off Publ Wound Heal Soc Eur Tissue Repair Soc. 2015;23:644–56.

    Google Scholar 

  69. Dhall S, Do D, Garcia M, Wijesinghe DS, Brandon A, Kim J, Sanchez A, Lyubovitsky J, Gallagher S, Nothnagel EA, Chalfant CE, Patel RP, Schiller N, Martins-Green M. A novel model of chronic wounds: importance of redox imbalance and biofilm-forming bacteria for establishment of chronicity. PLoS One. 2014;9:e109848.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Lima EO, de Macedo CS, Esteves CZ, de Oliveira DN, Pessolani MC, Nery JA, Sarno EN, Catharino RR. Skin imprinting in silica plates: a potential diagnostic methodology for leprosy using high-resolution mass spectrometry. Anal Chem. 2015;87:3585–92.

    Article  CAS  Google Scholar 

  71. Hart PJ, Francese S, Claude E, Woodroofe MN, Clench MR. MALDI-MS imaging of lipids in ex vivo human skin. Anal Bioanal Chem. 2011;401:115–25.

    Article  CAS  PubMed  Google Scholar 

  72. Tfayli A, Jamal D, Vyumvuhore R, Manfait M, Baillet-Guffroy A. Hydration effects on the barrier function of stratum corneum lipids: Raman analysis of ceramides 2, III and 5. Analyst. 2013;138:6582–8.

    Article  CAS  PubMed  Google Scholar 

  73. Tfayli A, Guillard E, Manfait M, Baillet-Guffroy A. Raman spectroscopy: feasibility of in vivo survey of stratum corneum lipids, effect of natural aging. Eur J Dermatol EJD. 2012;22:36–41.

    CAS  PubMed  Google Scholar 

  74. Chrit L, Hadjur C, Morel S, Sockalingum G, Lebourdon G, Leroy F, Manfait M. In vivo chemical investigation of human skin using a confocal Raman fiber optic microprobe. J Biomed Opt. 2005;10:44007.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

Research reported in this publication was supported by research grants from National Institutes of Health under grant numbers HD087198 (DSW). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Additionally, this work was also supported by a Career Development Award 1 (to DSW) and via a Young Investigator Award from SCIEX for clinical lipidomic research (DSW). The project was also supported by CTSA award number UL1TR000058 from the National Center for Advancing Translational Sciences which provides tuition and stipend funds to UOW. Lastly, services and products in support of the research project were generated by the VCU Massey Cancer Center Lipidomics Shared Resource [Developing Core], supported, in part, with funding from NIH-NCI Cancer Center Support Grant P30 CA016059 as well as a shared resource grant [S10RR031535] from the National Institutes of Health. The contents of this manuscript do not represent the views of the Department of Veterans Affairs, National Center for Advancing Translational Sciences or the National Institutes of Health, the National Institute of Health nor the United States Government. We graciously acknowledge the generosity of Dr. Chalfant in allowing us to use the ceramide data generated by us and depicted in Fig. 1.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Dayanjan S. Wijesinghe.

Ethics declarations

Conflict of Interest

Dayanjan S Wijesinghe, Urszula Osinska Warncke, and Robert F. Diegelmann declare that they have no conflicts of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with animal subjects performed by any of the authors. All human studies were carried out under the approval of the Institutional Review Board (IRB) of VCU-School of Medicine (IRB number 11087) and written informed consent was obtained from all participants.

Additional information

This article is part of the Topical Collection on Wound Care and Healing

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wijesinghe, D.S., Warncke, U.O. & Diegelmann, R.F. Human as the Ultimate Wound Healing Model: Strategies for Studies Investigating the Dermal Lipidome. Curr Derm Rep 5, 244–251 (2016). https://doi.org/10.1007/s13671-016-0156-3

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13671-016-0156-3

Keywords

Navigation