Engineered skin substitutes (ESSs) have been reported to close full-thickness burn wounds but are subject to loss from mechanical shear due to their deficiencies in tensile strength and elasticity. Hypothetically, if the mechanical properties of ESS matched those of native skin, losses due to shear or fracture could be reduced. To consider modifications of the composition of ESS to improve homology with native skin, biomechanical analyses of the current composition of ESS were performed. ESSs consist of a degradable biopolymer scaffold of type I collagen and chondroitin-sulfate (CGS) that is populated sequentially with cultured human dermal fibroblasts (hF) and epidermal keratinocytes (hK). In the current study, the hydrated biopolymer scaffold (CGS), the scaffold populated with hF dermal skin substitute (DSS), or the complete ESS were evaluated mechanically for linear stiffness (N/mm), ultimate tensile load at failure (N), maximum extension at failure (mm), and energy absorbed up to the point of failure (N-mm). These biomechanical end points were also used to evaluate ESS at six weeks after grafting to full-thickness skin wounds in athymic mice and compared to murine autograft or excised murine skin. The data showed statistically significant differences (p <0.05) between ESS in vitro and after grafting for all four structural properties. Grafted ESS differed statistically from murine autograft with respect to maximum extension at failure, and from intact murine skin with respect to linear stiffness and maximum extension. These results demonstrate rapid changes in mechanical properties of ESS after grafting that are comparable to murine autograft. These values provide instruction for improvement of the biomechanical properties of ESS in vitro that may reduce clinical morbidity from graft loss.

References

References
1.
Supp
,
D. M.
, and
Boyce
,
S. T.
,
2005
, “
Engineered Skin Substitutes: Practices and Potentials
,”
Clin. Dermatol.
,
23
(
4
), pp.
403
412
.10.1016/j.clindermatol.2004.07.023
2.
Boyce
,
S. T.
,
2004
, “
Fabrication, Quality Assurance, and Assessment of Cultured Skin Substitutes for Treatment of Skin Wounds
,”
Biochem. Eng. J.
,
20
(
2
), pp.
107
112
,
2004
.10.1016/j.bej.2003.09.017
3.
American Burn Association
,
2013
National Burn Repository, American Burn Association, Chicago, IL.
4.
MacNeil
,
S.
,
2007
, “
Progress and Opportunities for Tissue-Engineered Skin
,”
Nature
,
445
(
7130
), pp.
874
880
,
2007
.10.1038/nature05664
5.
Zeng
,
Q.
,
Macri
,
L. K.
,
Prasad
,
A.
,
Clark
,
R. A. F.
,
Zeugolis
,
D. I.
,
Hanley
,
C.
,
Garcia
,
Y.
, and
Pandit
,
A.
,
2011
, “
Skin Tissue Engineering
”,
Comprehensive Biomaterials
,
P.
Ducheyne
,
K.
Healy
,
D. E.
Hutmacher
,
D. W.
Grainger
, and
C. J.
Kirkpatrick
, eds.,
Elsevier
,
Philadelphia, PA
, pp.
467
499
.
6.
Boyce
,
S. T.
,
Kagan
,
R. J.
,
Greenhalgh
,
D. G.
,
Warner
,
P.
,
Yakuboff
,
K. P.
,
Palmieri
,
T.
, and
Warden
,
G. D.
,
2006
, “
Cultured Skin Substitutes Reduce Requirements for Harvesting of Skin Autograft for Closure of Excised Full-Thickness Burns
,”
J. Trauma
,
60
(
4
), pp.
821
829
.10.1097/01.ta.0000196802.91829.cc
7.
Brusselaers
,
N.
,
Pirayesh
,
A.
,
Hoeksema
,
H.
,
Richters
,
C. D.
,
Verbelen
,
J.
,
Beele
,
H.
,
Stijn
,
I. B.
, and
Monstrey
,
S.
,
2010
, “
Skin Replacement in Burn Wounds
,”
J. Trauma
,
68
(
2
), pp.
490
501
.10.1097/TA.0b013e3181c9c074
8.
Powell
,
H. M.
,
McFarland
,
K. L.
,
Butler
,
D. L.
,
Supp
,
D. M.
, and
Boyce
,
S. T.
,
2009
, “
Uniaxial Strain Regulates Morphogenesis, Gene Expression, and Tissue Strength in Engineered Skin
,
Tissue Eng. A.
,
16
(
3
), pp.
1083
1092
.10.1089/ten.tea.2009.0542
9.
Boyce
,
S. T.
,
Supp
,
A. P.
,
Wickett
,
R. R.
,
Hoath
,
S. B.
, and
Warden
,
G. D.
,
2000
, “
Assessment With the Dermal Torque Meter of Skin Pliability After Treatment of Burns With Cultured Skin Substitutes
,”
J. Burn Care Res.
,
21
(
1
), pp.
55
63
.
10.
Grenier
,
G.
,
Remy-Zolghadri
,
M.
,
Larouche
,
D.
,
Gauvin
,
R.
,
Baker
,
K.
,
Bergeron
,
F.
,
Dupuis
,
D.
,
Langelier
,
E.
,
Rancourt
,
D.
,
Auger
,
F. A.
, and
Germain
,
L.
,
2005
, “
Tissue Reorganization in Response to Mechanical Load Increases Functionality
,”
TIssue Eng.
,
11
(
1–2
), pp.
90
100
.10.1089/ten.2005.11.90
11.
Boyce
,
S. T.
,
Kagan
,
R. J.
,
Yakuboff
,
K. P.
,
Meyer
,
N. A.
,
Rieman
,
M. T.
,
Greenhalgh
,
D. G.
, and
Warden
,
G. D.
, “
Cultured Skin Substitutes Reduce Donor Skin Harvesting for Closure of Excised, Full Thickness Burns
,”
Ann. Surg.
,
235
(
2
), pp.
269
279
.10.1097/00000658-200202000-00016
12.
Boyce
,
S. T.
,
Kagan
,
R. J.
,
Meyer
,
N. A.
,
Yakuboff
,
K. P.
, and
Warden
,
G. D.
,
1999
, “
The 1999 Clinical Research Award. Cultured Skin Substitutes Combined With Integra Artificial Skin to Replace native Skin Autograft and Allograft for the Closure of Excised Full-Thickness Burns
,”
J. Burn Care Rehabil.
,
20
(
6
), pp.
453
461
.10.1097/00004630-199920060-00006
13.
Swope
, V
. B.
,
Supp
,
A. P.
, and
Boyce
,
S. T.
,
2002
, “
Regulation of Cutaneous Pigmentation by Titration of Human Melanocytes in Cultured Skin Substitutes Grafted to Athymic Mice
,”
Wound Rep. Regen.
,
10
(
6
), pp.
378
386
.10.1046/j.1524-475X.2002.10607.x
14.
Boyce
,
S. T.
,
Supp
,
A. P.
,
Swope
,
V. B.
,
Warden
,
G. D.
,
2002
,
Vitamin C Regulates Keratinocyte Viability, Epidermal Barrier, and Basement Membrane In Vitro, and Reduces Wound Contraction After Grafting of Cultured Skin Substitutes
,”
J. Invest. Dermatol.
,
118
(
4
), pp.
565
572
.10.1046/j.1523-1747.2002.01717.x
15.
Boyce
,
S. T.
,
1999
, “
Methods for the Serum-Free Culture of Keratinocytes and Transplantation of Collagen-GAG-Based Skin Substitutes
,”
Tissue Engineering Methods and Protocols Totowa
,
J.
Morgan
and
M.
Yarmush
, eds.,
Humana Press Inc.
,
New Jersey
, pp.
365
389
.
16.
Boyce
,
S. T.
, and
Ham
,
R. G.
,
1983
, “
Calcium-Regulated Differentiation of Normal Human Epidermal Keratinocytes in Chemically Defined Clonal Culture and Serum-Free Serial Culture
,”
J. Invest. Dermatol.
,
81
, pp.
33s
40s
.10.1111/1523-1747.ep12540422
17.
Shipley
,
G. D.
, and
Pittelkow
,
M. R.
,
1987
, “
Control of Growth and Differentiation In Vitro of Human Keratinocytes Cultured in Serum-Free Medium
,”
Arch. Dermatol.
,
123
(
11
), pp.
1541a
1544a
.10.1001/archderm.1987.01660350148032
18.
Boyce
,
S. T.
,
Christianson
,
D. J.
,
Hansbrough
,
J. F.
,
1988
, “
Structure of a Collagen-GAG Dermal Skin Substitute Optimized for Cultured Human Epidermal Keratinocytes
,”
J. Biomed. Mater. Res.
,
22
(
10
), pp.
939
957
.10.1002/jbm.820221008
19.
Boyce
,
S. T.
,
Foreman
,
T. J.
,
English
,
K. B.
,
Stayner
,
N.
,
Cooper
,
M. L.
,
Sakabu
,
S.
, and
Hansbrough
,
J. F.
,
1991
, “
Skin Wound Closure in Athymic Mice with Cultured Human Cells, Biopolymers, and Growth Factors
,”
Surgery
,
110
(5), pp.
866
876
.
20.
Quinn
,
K. P.
, and
Winkelstein
,
B. A.
,
2007
, “
Cervical Facet Capsular Ligament Yield Defines the Threshold for Injury and Persistent Joint-Mediated Neck Pain
,”
J. Biomech.
,
40
(
10
), pp.
2299
2306
.10.1016/j.jbiomech.2006.10.015
21.
Alperin
,
M.
,
Debes
,
K.
,
Abramowitch
,
S.
,
Meyn
,
L.
, and
Moalli
,
P. A.
,
2008
, “
LOXL1 Deficiency Negatively Impacts the Biomechanical Properties of the Mouse Vagina and Supportive Tissues
,”
Int. Urogynecol. J.
,
19
(
7
), pp.
977
986
.10.1007/s00192-008-0561-7
22.
Gibran
,
N. S.
,
Wiechman
,
S.
,
Meyer
,
W.
,
Edelman
,
L.
,
Fauerbach
,
J.
,
Gibbons
,
L.
,
Holavanahalli
,
R.
,
Hunt
,
C.
,
Keller
,
K.
,
Kirk
,
E.
,
Laird
,
J.
,
Lewis
,
G.
,
Moses
,
S.
,
Sproul
,
J.
,
Wilkinson
,
G.
,
Wolf
,
S.
,
Young
,
A.
,
Yovino
,
S.
,
Mosier
,
M. J.
,
Cancio
,
L. C.
,
Amani
,
H.
,
Blayney
,
C.
,
Cullinane
,
J.
,
Haith
,
L.
,
Jeng
,
J. C.
,
Kardos
,
P.
,
Kramer
,
G.
,
Lawless
,
M. B.
,
Serio-Melvin
,
M. L.
,
Miller
,
S.
,
Moran
,
K.
,
Novakovic
,
R.
,
Potenza
,
B.
,
Rinewalt
,
A.
,
Schultz
,
J.
,
Smith
,
H.
,
Dylewski
,
M.
,
Wibbenmeyer
,
L.
,
Bessey
,
P. Q.
,
Carter
,
J.
,
Gamelli
,
R.
,
Goodwin
,
C.
,
Graves
,
T.
,
Hollowed
,
K.
,
Holmes
,
J.
4th
,
Noordenbas
,
J.
,
Nordlund
,
M.
,
Savetamal
,
A.
,
Simpson
,
P.
,
Traber
,
D.
,
Traber
,
L.
,
Nedelec
,
B.
,
Donelan
,
M.
,
Baryza
,
M. J.
,
Bhavsar
,
D.
,
Blome-Eberwein
S.
,
Carrougher
,
G. J.
,
Hickerson
,
W.
,
Joe
,
V.
,
Jordan
,
M.
,
Kowalske
,
K.
,
Murray
,
D.
,
Murray
,
V. K.
,
Parry
,
I.
,
Peck
,
M.
,
Reilly
,
D.
,
Schneider
,
J. C.
,
Ware
,
L.
,
Singer
,
A. J.
,
Boyce
,
S. T.
,
Ahrenholz
,
D. H.
,
Chang
,
P.
,
Clark
,
R. A.
,
Fey
,
R.
,
Fidler
,
P.
,
Garner
,
W.
,
Greenhalgh
,
D.
,
Honari
,
S.
,
Jones
,
L.
,
Kagan
,
R.
,
Kirby
,
J.
,
Leggett
,
J.
,
Meyer
,
N.
,
Reigart
,
C.
,
Richey
,
K.
,
Rosenberg
,
L.
,
Weber
,
J.
,
Wiggins
,
B.
,
2013
, “
American Burn Association Consensus Statements
,”
J. Burn Care Res.
,
34
(
4
), pp.
361
385
.10.1097/BCR.0b013e31828cb249
23.
Cua
,
A.
,
Wilhelm
,
K. P.
, and
Maibach
,
H.
,
1990
, “
Elastic Properties of Human Skin: Relation to Age, Sex, and Anatomical Region
,”
Arch. Dermatol. Res.
,
282
(
5
), pp.
283
288
.10.1007/BF00375720
24.
Lanir
,
Y.
,
1987
, “
Skin Mechanics
,”
Handbook of Bioengineering
,
R.
Skalak
and
S.
Chien
, eds.,
McGraw-Hill
,
Dallas, TX
, pp.
11
25
.
25.
Ní Annaidh
,
A.
,
Bruyère
,
K.
,
Destrade
,
M.
,
Gilchrist
,
M. D.
, and
Otténio
,
M.
,
2012
, “
Characterization of the Anisotropic Mechanical Properties of Excised Human Skin
,”
J. Mech. Behav. Biomed. Mater.
,
5
(
1
), pp.
139
148
.10.1016/j.jmbbm.2011.08.016
26.
Oxlund
,
H.
,
Manschot
,
J.
, and
Viidik
,
A.
,
1988
, “
The Role of Elastin in the Mechanical Properties of Skin
,”
J. Biomech.
,
21
(
3
), pp.
213
218
.10.1016/0021-9290(88)90172-8
27.
Lafrance
,
H.
,
Yahia
,
L.
,
Germain
,
L.
,
Guillot
,
M.
, and
Auger
,
F. A.
,
1995
, “
Study of the Tensile Properties of Living Skin Equivalents
,”
Biomed. Mater. Eng.
,
5
(
4
), pp.
195
208
.10.3233/BME-1995-5401
28.
Sander
,
E. A.
and
Barocas
,
V. H.
,
2008
, “
Biomimetic Collagen Tissues: Collagenous Tissue Engineering and Other Applications
,”
Collagen Structure and Mechanics
,
P.
Fratzl
, ed.,
Springer
,
New York, NY
, pp.
475
504
.
29.
Grinnell
,
F.
, and
Petroll
,
W. M.
,
2010
, “
Cell Motility and Mechanics in Three-Dimensional Collagen Matrices
,”
Ann. Rev. Cell Dev. Biol.
,
26
, pp.
335
361
.10.1146/annurev.cellbio.042308.113318
30.
Candi
,
E.
,
Schmidt
,
R.
, and
Melino
,
G.
,
2005
, “
The Cornified Envelope: A Model of Cell Death in the Skin
,”
Nature Rev. Molec. Cell Biol.
,
6
(
4
), pp.
328
340
.10.1038/nrm1619
31.
Fuchs
,
E.
, and
Cleveland
,
D. W.
,
1998
, “
A Structural Scaffolding of Intermediate Filaments in Health and Disease
,”
Science
,
279
(
5350
), pp.
514
519
.10.1126/science.279.5350.514
32.
Ebersole
,
G.
,
Anderson
,
P.
, and
Powell
,
H.
,
2010
, “
Epidermal Differentiation Governs Engineered Skin Biomechanics
,”
J. Biomech.
,
43
(
16
), pp.
3183
3190
.10.1016/j.jbiomech.2010.07.026
33.
Jansen
,
L.
, and
Rottier
,
P.
,
1958
, “
Some Mechanical Properties of Human Abdominal Skin Measured on Excised Strips
,”
Dermatol.
,
117
(
2
), pp.
65
83
.10.1159/000255569
34.
Berthod
,
F.
,
Germain
,
L.
,
Li
,
H.
,
Xu
,
W.
,
Damour
,
O.
, and
Auger
,
F. A.
,
2001
, “
Collagen Fibril Network and Elastic System Remodeling in a Reconstructed Skin Transplanted on Nude Mice
,”
Matrix Biol.
,
20
(
7
), pp.
463
473
.10.1016/S0945-053X(01)00162-7
35.
Robb
,
E. C.
,
Bechmann
,
N.
,
Plessinger
,
R. T.
,
Boyce
,
S. T.
,
Warden
,
G. D.
, and
Kagan
,
R. J.
, “
Storage Media and Temperature Maintain Normal Anatomy of Cadaveric Human Skin for Transplantation to Full-Thickness Skin Wounds
,”
J. Burn Care Res.
,
22
(
6
), pp.
393
396
.
36.
Holbrook
,
K. A.
, and
Byers
,
P. H.
,
1989
, “
Skin Is a Window on Heritable Disorders of Connective Tissue
,”
Am. J. Med. Genet.
,
34
(
1
), pp.
105
121
.10.1002/ajmg.1320340118
37.
Bateman
,
J. F.
,
Boot-Handford
,
R. P.
, and
Lamandé
,
S. R.
,
2009
, “
Genetic Diseases of Connective Tissues: Cellular and Extracellular Effects of ECM Mutations
,”
Nature Rev. Genetics
,
10
(
3
), pp.
173
183
.10.1038/nrg2520
38.
Sander
,
E. A.
,
Stylianopoulos
,
T.
,
Tranquillo
,
R. T.
, and
Barocas
, V
. H.
,
2009
, “
Image-Based Multiscale Modeling Predicts Tissue–Level and Network-Level Fiber Reorganization in Stretched Cell-Compacted Collagen Gels
,”
Proc. Nat. Acad. Sci. USA
,
106
(
42
), pp.
17675
17680
.10.1073/pnas.0903716106
39.
Hadi
,
M. F.
,
Sander
,
E. A.
, and
Barocas
,
V. H.
,
2012
, “
Multiscale Model Predicts Tissue-Level Failure From Collagen Fiber-Level Damage
,”
ASME J. Biomech. Eng.
,
134
(
9
), pp.
091005
.10.1115/1.4007097
40.
Sander
,
E. A.
,
Barocas
,
V. H.
, and
Tranquillo
,
R. T.
,
2011
, “
Initial Fiber Alignment Pattern Alters Extracellular Matrix Synthesis in Fibroblast-Populated Fibrin Gel Cruciforms and Correlates With Predicted Tension
,”
Ann. Biomed. Eng.
,
2011
, pp.
1
16
10.1007/s10439-010-0192-2.
41.
Cicchi
,
R.
,
Kapsokalyvas
,
D.
,
De Giorgi
,
V.
,
Maio
,
V.
,
Van Wiechen
,
A.
,
Massi
,
D.
,
Lotti
,
T.
, and
Pavone
,
F. S.
,
2010
, “
Scoring of Collagen Organization in Healthy and Diseased Human Dermis by Multiphoton Microscopy
,”
J. Biophotonics,
3
(
1–2
), pp.
34
43
.10.1002/jbio.200910062
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