e187
Reconstructive surgery applies several methods to
cover acute or chronic wounds. Current options for
coverage of skin defects include not only the stan-
dard procedure, which is split- or full-thickness skin
grafting,
1
but also the use of skin substitutes.
2
Prod-
ucts currently applied and commercially available in
clinical routine are acellular collagen dermal matrices
(eg, Integra
®
, Matriderm
®
) or epidermal substitutes
(Epicel
®
, Epibase
®
). Skin substitutes were extensively
reviewed by Shevchenko et al
3
and most of them
specifically lack properties of full-thickness skin, that
is, color match, skin appendices, pliability, elasticity,
and most of all mechanical stability.
4
It is obvious,
that until today no successful full-thickness skin sub-
stitute design has been achieved. The presently avail-
able full-thickness constructs usually acquire only
insufficient blood supply, leading to cell death in
the substitute. Strategies to overcome this problem
include prevascularization of skin substitutes,
5
bio-
printing and electrospinning of biomaterials includ-
ing application of defined growth factor cocktails,
6
and finally the use of stem cells.
7,8
All these strategies
aim at speeding up the time until skin substitutes
obtain sufficient blood supply and cellular composi-
tion. In the clinical setting, surplus harvested skin
Copyright © 2013 by the American Burn Association
1559-047X/2014
DOI: 10.1097/BCR.0b013e3182a226df
Surplus harvested skin grafts are routinely stored at 4 to 6°C in saline for several days in
plastic surgery. The purpose of this study was to evaluate the influence of storage on human
skin graft performance in an in vivo intravital microscopic setting after transplantation.
Freshly harvested human full-thickness skin grafts and split-thickness skin grafts (STSGs)
after storage of 0, 3, or 7 days in moist saline at 4 to 6°C were transplanted into the
modified dorsal skinfold chamber, and intravital microscopy was performed to evaluate
vessel morphology and angiogenic change of the wound bed. The chamber tissue was
harvested 10 days after transplantation for evaluation of tissue integrity and inflammation
(hematoxylin and eosin) as well as for immunohistochemistry (human CD31, murine
CD31, Ki67, Tdt-mediated dUTP-biotin nick-end labelling). Intravital microscopy results
showed no differences in the host angiogenic response between fresh and preserved grafts.
However, STSGs and full-thickness skin grafts exhibited a trend toward different timing
and strength in capillary widening and capillary bud formation. Preservation had no
influence on graft quality before transplantation, but fresh STSGs showed better quality
10 days after transplantation than 7-day preserved grafts. Proliferation and apoptosis as
well as host capillary in-growth and graft capillary degeneration were equal in all groups.
These results indicate that cells may activate protective mechanisms under cold conditions,
allowing them to maintain function and morphology. However, rewarming may disclose
underlying tissue damage. These findings could be translated to a new approach for
the design of full-thickness skin substitutes. (J Burn Care Res 2014;35:e187–e196)
From the *Division of Plastic and Reconstructive Surgery, Depart-
ment of Surgery, University Hospital Zurich, Switzerland;
†Division of Dermatology, University Hospital Zurich, Switzer-
land; ‡Clinic for Cardiovascular Surgery, University Hospital
Zurich, Switzerland; and §Institute for Experimental Surgery,
University of Rostock, Germany.
This study was financially supported by the Swiss National Science
Foundation (SNF-Grant 310030_127366).
Address correspondence to Nicole Lindenblatt, MD, Division of
Plastic and Reconstructive Surgery, Department of Surgery,
University Hospital Zurich, Raemistrasse 100, 8091 Zurich,
Switzerland.
In Vivo Evaluation of Wound Bed Reaction and Graft
Performance After Cold Skin Graft Storage: New
Targets for Skin Tissue Engineering
Alicia Knapik, MSc,* Kai Kornmann,* Katrin Kerl, MD,† Maurizio Calcagni, MD,*
Christian A. Schmidt, MD, PhD,‡ Brigitte Vollmar, MD,§ Pietro Giovanoli, MD,*
Nicole Lindenblatt, MD*
ORIGINAL ARTICLE