Skin substitutes with noncultured autologous skin cell suspension heal porcine full-thickness wounds in a one-stage procedure.

Sita M Damaraju, Benjamin R Mintz, J Genevieve Park, Ankur Gandhi, Sunil Saini, Joseph A Molnar
Author Information
  1. Sita M Damaraju: Product Development, Integra LifeSciences, Corp, Princeton, New Jersey, USA. ORCID
  2. Benjamin R Mintz: Product Development, Integra LifeSciences, Corp, Princeton, New Jersey, USA.
  3. J Genevieve Park: Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA. ORCID
  4. Ankur Gandhi: Product Development, Integra LifeSciences, Corp, Princeton, New Jersey, USA.
  5. Sunil Saini: Product Development, Integra LifeSciences, Corp, Princeton, New Jersey, USA.
  6. Joseph A Molnar: Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.

Abstract

Clinical application of skin substitute is typically a two-stage procedure with application of skin substitute matrix to the wound followed by engraftment of a split-thickness skin graft (STSG). This two-stage procedure requires multiple interventions, increasing the time until the wound is epithelialised. In this study, the feasibility of a one-stage procedure by combining bioengineered collagen-chondroitin-6-sulfate (DS1) or decellularised fetal bovine skin substitute (DS2) with autologous skin cell suspension (ASCS) in a porcine full-thickness wound healing model was evaluated. Twelve full-thickness excisional wounds on the backs of pigs received one of six different treatments: empty; ASCS; DS1 with or without ASCS; DS2 with or without ASCS. The ASCS was prepared using a point-of-care device and was seeded onto the bottom side of DS1, DS2, and empty wounds at 80 000 cells/cm . Wound measurements and photographs were taken on days 0, 9, 14, 21, 28, 35, and 42 post-wounding. Histological analysis was performed on samples obtained on days 9, 14, 28, and 42. Wounds in the empty group or with ASCS alone showed increased wound contraction, fibrosis, and myofibroblast density compared with other treatment groups. The addition of ASCS to DS1 or DS2 resulted in a marked increase in re-epithelialisation of wounds at 14 days, from 15 ± 11% to 71 ± 20% (DS1 vs DS1 + ASCS) or 28 ± 14% to 77 ± 26 (DS2 vs DS2 + ASCS) despite different mechanisms of tissue regeneration employed by the DS used. These results suggest that this approach may be a viable one-stage treatment in clinical practice.

Keywords

References

  1. Int Wound J. 2022 Jan;19(1):188-201 [PMID: 34036743]
  2. Biotechnol Bioeng. 2005 Sep 5;91(5):607-15 [PMID: 16025534]
  3. J Cell Sci. 1994 Aug;107 ( Pt 8):2285-9 [PMID: 7983187]
  4. Br J Surg. 2015 Jan;102(2):e117-23 [PMID: 25627123]
  5. Plast Reconstr Surg. 1998 May;101(6):1572-9 [PMID: 9583488]
  6. Plast Reconstr Surg. 2015 Oct;136(4):524e-530e [PMID: 26397272]
  7. Plast Reconstr Surg Glob Open. 2020 Feb 24;8(2):e2622 [PMID: 32309075]
  8. Br J Plast Surg. 1999 Mar;52(2):127-32 [PMID: 10434892]
  9. Int Wound J. 2018 Oct;15(5):695-706 [PMID: 29590523]
  10. Burns. 2018 Dec;44(8):2011-2017 [PMID: 30104050]
  11. Burns. 2010 May;36(3):305-21 [PMID: 19897310]
  12. Cureus. 2017 Oct 2;9(10):e1736 [PMID: 29209583]
  13. Biomed Mater. 2015 Dec 23;11(1):014106 [PMID: 26694657]
  14. J Bone Joint Surg Am. 2006 Dec;88(12):2673-86 [PMID: 17142418]
  15. J Invest Dermatol. 1998 Jun;110(6):908-16 [PMID: 9620298]
  16. Burns. 2007 Sep;33(6):693-700 [PMID: 17485177]
  17. Burns. 2012 Feb;38(1):44-51 [PMID: 22079538]
  18. Wound Repair Regen. 2003 Mar-Apr;11(2):132-8 [PMID: 12631301]
  19. Proc Natl Acad Sci U S A. 1989 Feb;86(3):933-7 [PMID: 2915988]
  20. Burns. 2012 Sep;38(6):820-9 [PMID: 22652473]
  21. Adv Ther. 2019 Jul;36(7):1715-1729 [PMID: 31065995]
  22. Biotechnol Genet Eng Rev. 2010;26:163-78 [PMID: 21415880]
  23. Int J Biomater. 2013;2013:527957 [PMID: 23970899]
  24. PLoS One. 2017 Mar 31;12(3):e0174579 [PMID: 28362844]
  25. PLoS One. 2015 Mar 23;10(3):e0120322 [PMID: 25798623]
  26. Adv Drug Deliv Rev. 2018 Jan 1;123:18-32 [PMID: 28668483]
  27. Clin Cosmet Investig Dermatol. 2014 Nov 06;7:301-11 [PMID: 25395868]
  28. Skin Res Technol. 1995 May;1(2):74-80 [PMID: 27328386]
  29. J Burns Wounds. 2005 Mar 14;4:e4 [PMID: 16921409]
  30. Adv Drug Deliv Rev. 2018 Jan 1;123:3-17 [PMID: 28941987]
  31. Nature. 2000 Sep 14;407(6801):249-57 [PMID: 11001068]
  32. Int Wound J. 2016 Aug;13(4):540-53 [PMID: 26250714]

Grants

  1. /Integra LifeSciences

MeSH Term

Animals
Cattle
Re-Epithelialization
Skin Transplantation
Skin, Artificial
Swine
Transplantation, Autologous
Wound Healing

Word Cloud

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