Decellularized bSIS-ECM as a Regenerative Biomaterial for Skin Wound Repair

  • Mahmut Parmaksiz
  • Ayşe Eser Elçin
  • Yaşar Murat ElçinEmail author
Part of the Methods in Molecular Biology book series (MIMB, volume 1879)


Tissue engineering-based regenerative applications can involve the use of stem cells for the treatment of non-healing wounds. Multipotent mesenchymal stem cells have become a focus of skin injury treatments along with many other injury types owing to their unprecedented advantages. However, there are certain limitations concerning the solo use of stem cells in skin wound repair. Natural bioactive extracellular matrix-based scaffolds have great potential for overcoming these limitations by supporting the regenerative activity and localization of stem cells. This chapter describes the use of bone marrow mesenchymal stem cells together with decellularized bovine small intestinal submucosa (SIS), for the treatment of a critical-sized full-thickness skin defect in a small animal model.


Critical-sized skin defect Extracellular matrix (ECM) Full-thickness wound repair Mesenchymal stem cells (MSCs) Small intestinal submucosa (SIS) Xenogenic biomaterials 


Competing Interests

The authors have intellectual properties related to decellularized tissues. Y.M.E. is the founder and director of Biovalda, Inc. (Ankara, Turkey).


  1. 1.
    Tartarini D, Mele E (2015) Adult stem cell therapies for wound healing: biomaterials and computational models. Front Bioeng Biotechnol 3:206PubMedGoogle Scholar
  2. 2.
    Parmaksiz M, Elcin AE, Elcin YM (2017) Decellularization of bovine small intestinal submucosa and its use for the healing of a critical-sized full-thickness skin defect, alone and in combination with stem cells, in a small rodent model. J Tissue Eng Regen Med 11(6):1754–1765CrossRefGoogle Scholar
  3. 3.
    Bielefeld KA, Amini-Nik S, Alman BA (2013) Cutaneous wound healing: recruiting developmental pathways for regeneration. Cell Mol Life Sci 70(12):2059–2081CrossRefGoogle Scholar
  4. 4.
    Metcalfe AD, Ferguson MW (2007) Tissue engineering of replacement skin: the crossroads of biomaterials, wound healing, embryonic development, stem cells and regeneration. J R Soc Interface 4(14):413–437CrossRefGoogle Scholar
  5. 5.
    Ho J, Walsh C, Yue D, Dardik A, Cheema U (2017) Current advancements and strategies in tissue engineering for wound healing: a comprehensive review. Adv Wound Care (New Rochelle) 6(6):191–209CrossRefGoogle Scholar
  6. 6.
    Ojeh N, Pastar I, Tomic-Canic M, Stojadinovic O (2015) Stem cells in skin regeneration, wound healing, and their clinical applications. Int J Mol Sci 16(10):25476–25501CrossRefGoogle Scholar
  7. 7.
    Chen M, Przyborowski M, Berthiaume F (2009) Stem cells for skin tissue engineering and wound healing. Crit Rev Biomed Eng 37(4–5):399–421CrossRefGoogle Scholar
  8. 8.
    Ito M, Liu Y, Yang Z, Nguyen J, Liang F, Morris RJ, Cotsarelis G (2005) Stem cells in the hair follicle bulge contribute to wound repair but not to homeostasis of the epidermis. Nat Med 11(12):1351–1354CrossRefGoogle Scholar
  9. 9.
    Odabas S, Elçin AE, Elçin YM (2014) Isolation and characterization of mesenchymal stem cells. Methods Mol Biol 1109:47–63CrossRefGoogle Scholar
  10. 10.
    Isakson M, de Blacam C, Whelan D, McArdle A, Clover AJP (2015) Mesenchymal stem cells and cutaneous wound healing: current evidence and future potential. Stem Cells Int 2015:831095CrossRefGoogle Scholar
  11. 11.
    An Y, Wei W, Jing H, Ming L, Liu S, Jin Y (2015) Bone marrow mesenchymal stem cell aggregate: an optimal cell therapy for full-layer cutaneous wound vascularization and regeneration. Sci Rep 5:17036CrossRefGoogle Scholar
  12. 12.
    Su N, Gao PL, Wang K, Wang JY, Zhong Y, Luo Y (2017) Fibrous scaffolds potentiate the paracrine function of mesenchymal stem cells: a new dimension in cell-material interaction. Biomaterials 141:74–85CrossRefGoogle Scholar
  13. 13.
    Wu Y, Chen L, Scott PG, Tredget EE (2007) Mesenchymal stem cells enhance wound healing through differentiation and angiogenesis. Stem Cells 25:2648–2659CrossRefGoogle Scholar
  14. 14.
    Hocking AM (2012) Mesenchymal stem cell therapy for cutaneous wounds. Adv Wound Care (New Rochelle) 1(4):166–171CrossRefGoogle Scholar
  15. 15.
    Dogan A, Parmaksız M, Elçin AE, Elçin YM (2016) Extracellular matrix and regenerative therapies from the cardiac perspective. Stem Cell Rev 12(2):202–213CrossRefGoogle Scholar
  16. 16.
    Duscher D, Barrera J, Wong VW, Maan ZN, Whittam AJ, Januszyk M, Gurtner GC (2016) Stem cells in wound healing: the future of regenerative medicine? A mini-review. Gerontology 62:216–225CrossRefGoogle Scholar
  17. 17.
    Elçin YM (2004) Stem cells and tissue engineering. Adv Exp Med Biol 553:301–316CrossRefGoogle Scholar
  18. 18.
    Parmaksiz M, Dogan A, Odabas S, Elçin AE, Elçin YM (2016) Clinical applications of decellularized extracellular matrices for tissue engineering and regenerative medicine. Biomed Mater 11(2):022003CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2018

Authors and Affiliations

  • Mahmut Parmaksiz
    • 1
  • Ayşe Eser Elçin
    • 1
  • Yaşar Murat Elçin
    • 2
    • 3
    Email author
  1. 1.Tissue Engineering, Biomaterials and Nanobiotechnology LaboratoryAnkara University, Faculty of Science and Stem Cell InstituteAnkaraTurkey
  2. 2.Tissue Engineering, Biomaterials and Nanobiotechnology LaboratoryAnkara University, Faculty of ScienceAnkaraTurkey
  3. 3.Biovalda Health Technologies, Inc.AnkaraTurkey

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