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RETRACTED ARTICLE: Decellularized scaffolds containing hyaluronic acid and EGF for promoting the recovery of skin wounds

  • Tissue Engineering Constructs and Cell Substrates
  • Published:
Journal of Materials Science: Materials in Medicine Aims and scope Submit manuscript

This article was retracted on 26 May 2021

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Abstract

There is no effective therapy for the treatment of deep and large area skin wounds. Decellularized scaffolds can be prepared from animal tissues and represent a promising biomaterial for investigation in tissue regeneration studies. In this study, MTT assay showed that epidermal growth factor (EGF) increased NIH3T3 cell proliferation in a bell-shaped dose response, and the maximum cell proliferation was achieved at a concentration of 25 ng/ml. Decellularized scaffolds were prepared from pig peritoneum by a series of physical and chemical treatments. Hyaluronic acid (HA) increased EGF adsorption to the scaffolds. Decellularized scaffolds containing HA sustained the release of EGF compared to no HA. Rabbits contain relatively large skin surface and are less expensive and easy to be taken care, so that a rabbit wound healing model was use in this study. Four full-thickness skin wounds were created in each rabbit for evaluation of the effects of the scaffolds on the skin regeneration. Wounds covered with scaffolds containing either 1 or 3 μg/ml EGF were significantly smaller than with vaseline oil gauzes or with scaffolds alone, and the wounds covered with scaffolds containing 1 μg/ml EGF recovered best among all four wounds. Hematoxylin-Eosin staining confirmed these results by demonstrating that significantly thicker dermis layers were also observed in the wounds covered by the decellularized scaffolds containing HA and either 1 or 3 μg/ml EGF than with vaseline oil gauzes or with scaffolds alone. In addition, the scaffolds containing HA and 1 μg/ml EGF gave thicker dermis layers than HA and 3 μg/ml EGF and showed the regeneration of skin appendages on day 28 post-transplantation. These results demonstrated that decellularized scaffolds containing HA and EGF could provide a promising way for the treatment of human skin injuries.

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References

  1. Yannas IV, Kwan MD, Longaker MT. Early fetal healing as a model for adult organ regeneration. Tissue Eng. 2007;13(8):1789–98.

    CAS  Google Scholar 

  2. Pereira RF, Barrias CC, Granja PL, Bartolo PJ. Advanced biofabrication strategies for skin regeneration and repair. Nanomedicine (Lond). 2013;8(4):603–21.

    CAS  Google Scholar 

  3. Rose MT. Effect of growth factors on the migration of equine oral and limb fibroblasts using an in vitro scratch assay. Vet J. 2012;193(2):539–44.

    CAS  Google Scholar 

  4. Choi JK, Jang JH, Jang WH, Kim J, Bae IH, Bae J, Park YH, Kim BJ, Lim KM, Park JW. The effect of epidermal growth factor (EGF) conjugated with low-molecular-weight protamine (LMWP) on wound healing of the skin. Biomaterials. 2012;33(33):8579–90.

    CAS  Google Scholar 

  5. Hardwicke J, Ferguson EL, Moseley R, Stephens P, Thomas D, Duncan R. Dextrin–rhEGF conjugates as bioresponsive nanomedicines for wound repair. J Control Release. 2008;130(3):275–83.

    CAS  Google Scholar 

  6. Hardwicke JT, Hart J, Bell A, Duncan R, Thomas DW, Moseley R. The effect of dextrin–rhEGF on the healing of full-thickness, excisional wounds in the (db/db) diabetic mouse. J Control Release. 2011;152(3):411–7.

    CAS  Google Scholar 

  7. Shi HX, Lin C, Lin BB, Wang ZG, Zhang HY, Wu FZ, Cheng Y, Xiang LJ, Guo DJ, Luo X, Zhang GY, Fu XB, Bellusci S, Li XK, Xiao J. The anti-scar effects of basic fibroblast growth factor on the wound repair in vitro and in vivo. PLoS One. 2013;8(4):e59966.

    CAS  Google Scholar 

  8. Cowman MK, Matsuoka S. Experimental approaches to hyaluronan structure. Carbohydr Res. 2005;340(5):791–809.

    CAS  Google Scholar 

  9. Mineo A, Suzuki R, Kuroyanagi Y. Development of an artificial dermis composed of hyaluronic acid and collagen. J Biomater Sci Polym Ed. 2013;24(6):726–40.

    CAS  Google Scholar 

  10. Pasonen-Seppänen SM, Maytin EV, Törrönen KJ, Hyttinen JM, Hascall VC, MacCallum DK, Kultti AH, Jokela TA, Tammi MI, Tammi RH. All-trans retinoic acid-induced hyaluronan production and hyperplasia are partly mediated by EGFR signaling in epidermal keratinocytes. J Invest Dermatol. 2008;128(4):797–807.

    Google Scholar 

  11. Ferguson EL, Roberts JL, Moseley R, Griffiths PC, Thomas DW. Evaluation of the physical and biological properties of hyaluronan and hyaluronan fragments. Int J Pharm. 2011;420(1):84–92.

    CAS  Google Scholar 

  12. Huang L, Gu H, Burd A. A reappraisal of the biological effects of hyaluronan on human dermal fibroblast. J Biomed Mater Res A. 2009;90(4):1177–85.

    Google Scholar 

  13. Kondo S, Kuroyanagi Y. Development of a wound dressing composed of hyaluronic acid and collagen sponge with epidermal growth factor. J Biomater Sci Polym Ed. 2012;23(5):629–43.

    CAS  Google Scholar 

  14. Ferguson EL, Alshame AM, Thomas DW. Evaluation of hyaluronic acid–protein conjugates for polymer masked-unmasked protein therapy. Int J Pharm. 2010;402(1–2):95–102.

    CAS  Google Scholar 

  15. Steinstraesser L, Wehner M, Trust G, Sorkin M, Bao D, Hirsch T, Sudhoff H, Daigeler A, Stricker I, Steinau HU, Jacobsen F. Laser-mediated fixation of collagen-based scaffolds to dermal wounds. Lasers Surg Med. 2010;42(2):141–9.

    Google Scholar 

  16. Singh O, Gupta SS, Soni M, Moses S, Shukla S, Mathur RK. Collagen dressing versus conventional dressings in burn and chronic wounds: a retrospective study. J Cutan Aesthet Surg. 2011;4(1):12–6.

    Google Scholar 

  17. Singh R, Chackarkar MP. Dried gamma-irradiated amniotic membrane as dressing in burn wound care. J Tissue Viability. 2011;20(2):49–54.

    Google Scholar 

  18. Mathangi Ramakrishnan K, Babu M, Mathivanan Jayaraman V, Shankar J. Advantages of collagen based biological dressings in the management of superficial and superficial partial thickness burns in children. Ann Burns Fire Disasters. 2013;26(2):98–104.

    CAS  Google Scholar 

  19. Shevchenko RV, James SL, James SE. A review of tissue-engineered skin bioconstructs available for skin reconstruction. J R Soc Interface. 2010;7(43):229–58.

    CAS  Google Scholar 

  20. Barnes CP, Sell SA, Boland ED, Simpson DG, Bowlin GL. Nanofiber technology: designing the next generation of tissue engineering scaffolds. Adv Drug Deliv Rev. 2007;59(14):1413–33.

    CAS  Google Scholar 

  21. Atiyeh BS, Costagliola M. Cultured epithelial autograft (CEA) in burn treatment: three decades later. Burns. 2007;33(4):405–13.

    Google Scholar 

  22. Metcalfe AD, Ferguson MW. Tissue engineering of replacement skin: the crossroads of biomaterials, wound healing, embryonic development, stem cells and regeneration. J R Soc Interface. 2007;4(14):413–37.

    CAS  Google Scholar 

  23. Clark RA, Ghosh K, Tonnesen MG. Tissue engineering for cutaneous wounds. J Invest Dermatol. 2007;127(5):1018–29.

    CAS  Google Scholar 

  24. MacNeil S. Progress and opportunities for tissue-engineered skin. Nature. 2007;445(7130):874–80.

    CAS  Google Scholar 

  25. Patel M, Fisher JP. Biomaterial scaffolds in pediatric tissue engineering. Pediatr Res. 2008;63(5):497–501.

    Google Scholar 

  26. Brohem CA, Cardeal LB, Tiago M, Soengas MS, Barros SB, Maria-Engler SS. Artificial skin in perspective: concepts and applications. Pigment Cell Melanoma Res. 2011;24(1):35–50.

    Google Scholar 

  27. Li J, Chen J, Kirsner R. Pathophysiology of acute wound healing. Clin Dermatol. 2007;25(1):9–18.

    CAS  Google Scholar 

  28. Hardwicke J, Moseley R, Stephens P, Harding K, Duncan R, Thomas DW. Bioresponsive dextrin–rhEGF conjugates: in vitro evaluation in models relevant to its proposed use as a treatment for chronic wounds. Mol Pharm. 2010;7(3):699–707.

    CAS  Google Scholar 

  29. Torikai K, Ichikawa H, Hirakawa K, Matsumiya G, Kuratani T, Iwai S, Saito A, Kawaguchi N, Matsuura N, Sawa Y. A self-renewing, tissue-engineered vascular graft for arterial reconstruction. J Thorac Cardiovasc Surg. 2008;136(1):37–45.

    Google Scholar 

  30. Nauta AC, Grova M, Montoro DT, Zimmermann A, Tsai M, Gurtner GC, Galli SJ, Longaker MT. Evidence that mast cells are not required for healing of splinted cutaneous excisional wounds in mice. PLoS One. 2013;8(3):e59167.

    CAS  Google Scholar 

  31. Kondo T, Ishida Y. Molecular pathology of wound healing. Forensic Sci Int. 2010;203(1–3):93–8.

    CAS  Google Scholar 

  32. Lee KB, Choi J, Cho SB, Chung JY, Moon ES, Kim NS, Han HJ. Topical embryonic stem cells enhance wound healing in diabetic rats. J Orthop Res. 2011;29(10):1554–62.

    CAS  Google Scholar 

  33. Pastore S, Mascia F, Mariani V, Girolomoni G. The epidermal growth factor receptor system in skin repair and inflammation. J Invest Dermatol. 2008;128(6):1365–74.

    CAS  Google Scholar 

  34. Kimura A, Terao M, Kato A, Hanafusa T, Murota H, Katayama I, Miyoshi E. Upregulation of N-acetylglucosaminyltransferase-V by heparin-binding EGF-like growth factor induces keratinocyte proliferation and epidermal hyperplasia. Exp Dermatol. 2012;21(7):515–9.

    CAS  Google Scholar 

  35. Yang X, Wang J, Guo SL, Fan KJ, Li J, Wang YL, Teng Y, Yang X. miR-21 promotes keratinocyte migration and re-epithelialization during wound healing. Int J Biol Sci. 2011;7(5):685–90.

    CAS  Google Scholar 

  36. Değim Z, Çelebi N, Alemdaroğlu C, Deveci M, Öztürk S, Özoğul C. Evaluation of chitosan gel containing liposome-loaded epidermal growth factor on burn wound healing. Int Wound J. 2011;8(4):343–54.

    Google Scholar 

  37. Chin MS, Freniere BB, Bonney CF, Lancerotto L, Saleeby JH, Lo YC, Orgill DP, Fitzgerald TJ, Lalikos JF. Skin perfusion and oxygenation changes in radiation fibrosis. Plast Reconstr Surg. 2013;131(4):707–16.

    CAS  Google Scholar 

  38. Raghunath J, Rollo J, Sales KM, Butler PE, Seifalian AM. Biomaterials and scaffold design: key to tissue-engineering cartilage. Biotechnol Appl Biochem. 2007;46(Pt 2):73–84.

    CAS  Google Scholar 

  39. Espinosa L, Sosnik A, Fontanilla MR. Development and preclinical evaluation of acellular collagen scaffolding and autologous artificial connective tissue in the regeneration of oral mucosa wounds. Tissue Eng Part A. 2010;16(5):1667–79.

    CAS  Google Scholar 

  40. Yang Y, Xia T, Zhi W, Wei L, Weng J, Zhang C, Li X. Promotion of skin regeneration in diabetic rats by electrospun core sheath fibers loaded with basic fibroblast growth factor. Biomaterials. 2011;32(18):4243–54.

    CAS  Google Scholar 

  41. Banerjee I, Mishra D, Das T, Maiti TK. Wound pH-responsive sustained release of therapeutics from a poly (NIPAAm-co-AAc) hydrogel. J Biomater Sci Polym Ed. 2012;23(1–4):111–32.

    CAS  Google Scholar 

  42. Hong JP, Kim YW, Jung HD, Jung KI. The effect of various concentrations of human recombinant epidermal growth factor on split-thickness skin wounds. Int Wound J. 2006;3(2):123–30.

    Google Scholar 

  43. Ko J, Jun H, Chung H, Yoon C, Kim T, Kwon M, Lee S, Jung S, Kim M, Park JH. Comparison of EGF with VEGF non-viral gene therapy for cutaneous wound healing of streptozotocin diabetic mice. Diabetes Metab J. 2011;35(3):226–35.

    Google Scholar 

Download references

Acknowledgments

This work was supported by National Natural Science Foundation of China (Grant No. 30870650 and Grant No. 31171304 to Xing Wei), Research Foundation for Doctoral Discipline of Higher Education (Grant No. 20114401110007 to Xing Wei), and the Fundamental Research Funds for the Central Universities (Grant No. 21612107 to Xing Wei).

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    Authors and Affiliations

    1. Key Lab for Genetic Medicine of Guangdong Province, National Engineering Research Center of Genetic Medicine, Institute of Biomedicine, Jinan University, Guangzhou, 510632, Guangdong, China

      Zhengzheng Wu, Hongdou Fang, Zhongchun Su & Xing Wei

    2. Multidisciplinary Research Center, College of Science, Shantou University, Shantou, 515063, Guangdong, China

      Yan Tang

    3. Grandhope Biotech Co., Ltd., Building D, #408, Guangzhou International Business Incubator, Guangzhou Science Park, Guangzhou, 510663, Guangdong, China

      Bin Xu, Yongliang Lin & Peng Zhang

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    1. Zhengzheng Wu
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    Correspondence to Xing Wei.

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    Zhengzheng Wu, Yan Tang, Hongdou Fang and Zhongchun Su contributed equally to this paper.

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    Wu, Z., Tang, Y., Fang, H. et al. RETRACTED ARTICLE: Decellularized scaffolds containing hyaluronic acid and EGF for promoting the recovery of skin wounds. J Mater Sci: Mater Med 26, 59 (2015). https://doi.org/10.1007/s10856-014-5322-1

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    • DOI: https://doi.org/10.1007/s10856-014-5322-1

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