Skin plays a crucial role in many important physiologic functions including fluid homeostasis, sensory detection, and protection against extemal insults. Damage to skin represents a major clinical problem, and can result from multiple events such as mechanical trauma, bums, and pathologic conditions (e.g. cancer and diabetes). Autografting of skin is the gold standard of treatment for skin repair, however the amount of donor skin is in limited supply, and the quality of donor skin can be compromised in certain patients. Allografts and xenografted tissues are often used in place of autografts, however these substrates also present disadvantages including the possibility of immune reactivity and transfer of pathogens. For all of these reasons, there is currently intensive interest in generating alternative materials that can serve as skin substitutes, or as temporary supports that induce skin regeneration. The principal goal of the proposed research is to develop a biodegradable fibroblast-embedded matrix that mimics the architecture, mechanical properties, biochemistry and cellularity of skin and that con-espondingly stimulates skin tissue regeneration. To achieve this objective, our laboratory has developed a novel layer-by-layer electrospinning method to create a nanofibrous matrix with dermal fibroblasts distributed throughout the scaffold thickness. The nanofibers are composed of a blend of collagen 1, a principal constituent of the dermis, with polycaprolactone (PCL), a synthetic polymer that imparts mechanical strength to the matrix, and allows tuning of scaffold degradation rate. Preliminary studies suggest that scaffolds generated by this approach support the survival and proliferation of embedded fibroblasts, and also stimulate keratinocytes grown on the top of the scaffolds to undergo differentiation and formation of a stratefied epidermal layer.

Public Health Relevance

A large proportion of the US population experiences pain, infection, and/or disfiguration as a consequence of skin damage or disease. Autologous skin grafts comprise an effective treatment, however native skin is in limited supply. The proposed research aims to develop a readily available skin substitute that performs with equivalent, or even enhanced, clinical efficacy as compared with autologous grafts.

National Institute of Health (NIH)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Center Core Grants (P30)
Project #
Application #
Study Section
Special Emphasis Panel (ZAR1-KM-D)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Alabama Birmingham
United States
Zip Code
Pal, Harish Chandra; Athar, Mohammad; Elmets, Craig A et al. (2015) Fisetin inhibits UVB-induced cutaneous inflammation and activation of PI3K/AKT/NF?B signaling pathways in SKH-1 hairless mice. Photochem Photobiol 91:225-34
Nasti, Tahseen H; Timares, Laura (2015) MC1R, eumelanin and pheomelanin: their role in determining the susceptibility to skin cancer. Photochem Photobiol 91:188-200
Pal, H C; Chamcheu, J C; Adhami, V M et al. (2015) Topical application of delphinidin reduces psoriasiform lesions in the flaky skin mouse model by inducing epidermal differentiation and inhibiting inflammation. Br J Dermatol 172:354-64
Abdul Roda, Mojtaba; Sadik, Mariam; Gaggar, Amit et al. (2014) Targeting prolyl endopeptidase with valproic acid as a potential modulator of neutrophilic inflammation. PLoS One 9:e97594
Wells, J Michael; O'Reilly, Philip J; Szul, Tomasz et al. (2014) An aberrant leukotriene A4 hydrolase-proline-glycine-proline pathway in the pathogenesis of chronic obstructive pulmonary disease. Am J Respir Crit Care Med 190:51-61
Elmets, Craig A; Cala, Cather M; Xu, Hui (2014) Photoimmunology. Dermatol Clin 32:277-90, vii
Chaudhary, Sandeep C; Singh, Tripti; Talwelkar, Sarang S et al. (2014) Erb-041, an estrogen receptor-* agonist, inhibits skin photocarcinogenesis in SKH-1 hairless mice by downregulating the WNT signaling pathway. Cancer Prev Res (Phila) 7:186-98
Arumugam, Aadithya; Weng, Zhiping; Chaudhary, Sandeep C et al. (2014) Keratin-6 driven ODC expression to hair follicle keratinocytes enhances stemness and tumorigenesis by negatively regulating Notch. Biochem Biophys Res Commun 451:394-401
Brawner, Kyle M; Morrow, Casey D; Smith, Phillip D (2014) Gastric microbiome and gastric cancer. Cancer J 20:211-6
Elmets, Craig A; Ledet, Johnathan J; Athar, Mohammad (2014) Cyclooxygenases: mediators of UV-induced skin cancer and potential targets for prevention. J Invest Dermatol 134:2497-502

Showing the most recent 10 out of 142 publications