Tissue scaffolding is a key component for tissue engineering, and the extracellular matrix (ECM) is nature’s ideal scaffold material. A conceptually different method is reported here for producing tissue scaffolds by decellularization of living tissues using nonthermal irreversible electroporation (NTIRE) pulsed electrical fields to cause nanoscale irreversible damage to the cell membrane in the targeted tissue while sparing the ECM and utilizing the body’s host response for decellularization. This study demonstrates that the method preserves the native tissue ECM and produces a scaffold that is functional and facilitates recellularization. A two-dimensional transient finite element solution of the Laplace and heat conduction equations was used to ensure that the electrical parameters used would not cause any thermal damage to the tissue scaffold. By performing NTIRE in vivo on the carotid artery, it is shown that in 3 days post NTIRE the immune system decellularizes the irreversible electroporated tissue and leaves behind a functional scaffold. In 7 days, there is evidence of endothelial regrowth, indicating that the artery scaffold maintained its function throughout the procedure and normal recellularization is taking place.

1.
Campbell
,
G.
, and
Campbell
,
J.
, 2007, “
Development of Tissue Engineered Vascular Grafts
,”
Curr. Pharm. Biotechnol.
1389-2010,
8
, pp.
43
50
.
2.
Borschel
,
G.
,
Huang
,
Y. -C.
,
Calve
,
S.
,
Arruda
,
E. M.
,
Lynch
,
J. B.
,
Dow
,
D. E.
,
Kuzon
,
W. M.
,
Dennis
,
R. G.
, and
Brown
,
D. L.
, 2005, “
Tissue Engineering of Recellularized Small-Diameter Vascular Grafts
,”
Tissue Eng.
1076-3279,
11
(
5–6
), pp.
778
786
.
3.
Huynh
,
T.
,
Abraham
,
G.
,
Murray
,
J.
,
Brockbank
,
K.
,
Hagen
,
P. -O.
, and
Sullivan
,
S.
, 1999, “
Remodeling of an Acellular Collagen Graft Into a Physiologically Responsive Neovessel
,”
Nat. Biotechnol.
1087-0156,
17
, pp.
1083
1086
.
4.
Conklin
,
B.
,
Richter
,
R.
,
Kreutziger
,
K.
,
Zhong
,
D.
, and
Chen
,
C.
, 2002, “
Development and Evaluation of a Novel Decellularized Vascular Xenograft
,”
Med. Eng. Phys.
1350-4533,
24
, pp.
173
183
.
5.
L’Heureux
,
N.
,
Stoclet
,
J.
,
Auger
,
F.
,
Lagaud
,
G.
,
Germain
,
L.
, and
Andriantsitohaina
,
R.
, 2001, “
A Human Tissue-Engineered Vascular Media: A New Model for Pharmacological Studies of Contractile Responses
,”
FASEB J.
0892-6638,
15
, pp.
515
524
.
6.
Tranquillo
,
R.
,
Girton
,
T.
,
Branberek
,
B.
,
Triebes
,
T.
, and
Mooradian
,
D.
, 1996, “
Magnetically Oriented Tissue-Equivalent Tubes: Application to a Circumferentially Oriented Media-Equivalent
,”
Biomaterials
0142-9612,
17
, pp.
349
357
.
7.
Niklason
,
L.
,
Gao
,
J.
,
Abbott
,
W.
,
Hirschi
,
K.
,
Houser
,
S.
,
Marini
,
R.
, and
Langer
,
R.
, 1999, “
Functional Arteries Grown In Vitro
,”
Science
0036-8075,
284
(
5413
), pp.
489
493
.
8.
Gilbert
,
T.
,
Sellaro
,
T.
, and
Badylak
,
S.
, 2006, “
Decellularization of Tissues and Organs
,”
Biomaterials
0142-9612,
27
, pp.
3675
3683
.
9.
Yow
,
K.
,
Ingram
,
J.
,
Korossis
,
S.
,
Ingham
,
E.
, and
Homer-Vanniasinkam
,
S.
, 2006, “
Tissue Engineering of Vascular Conduits
,”
Br. J. Surg.
0007-1323,
93
, pp.
652
661
.
10.
Clarke
,
D.
,
Lust
,
R.
,
Sun
,
Y.
,
Black
,
K.
, and
Ollerenshaw
,
J.
, 2001, “
Transformation of Nonvascular Acellular Tissue Matrices Into Durable Vascular Conduits
,”
Ann. Thorac. Surg.
0003-4975,
71
, pp.
S433
S436
.
11.
Conconi
,
M.
,
De Coppi
,
P.
,
Di Liddo
,
R.
,
Vigolo
,
S.
,
Zanon
,
G. F.
,
Parnigotto
,
P. P.
, and
Nussdorfer
,
G. G.
, 2005, “
Tracheal Matrices, Obtained by a Detergent-Enzymatic Method, Support In Vitro the Adhesion of Chondrocytes and Tracheal Epithelial Cells
,”
Transpl Int.
0934-0874,
18
, pp.
727
734
.
12.
Flynn
,
L.
,
Semple
,
J.
, and
Woodhouse
,
K.
, 2006, “
Decellularized Placental Matrices for Adipose Tissue Engineering
,”
J. Biomed. Mater. Res. A
,
79
(
2
), pp.
359
369
.
13.
Ott
,
H.
,
et al.
, 2008, “
Perfusion-Decellularized Matrix: Using Nature’s Platform to Engineer a Bioartificial Heart
,”
Nat. Med.
1078-8956,
14
, pp.
213
221
.
14.
Badylak
,
S.
,
Kropp
,
B.
,
McPherson
,
T.
,
Liang
,
H.
, and
Snyder
,
P.
, 1998, “
Small Intestinal Submucosa: A Rapidly Resorbed Bioscaffold for Augmentation Cystoplasty in a Dog Model
,”
Tissue Eng.
1076-3279,
4
(
4
), pp.
379
387
.
15.
Liu
,
Y.
,
Bharadwaj
,
S.
,
Lee
,
S.
,
Atala
,
A.
, and
Zhang
,
Y.
, 2009, “
Optimization of a Natural Collagen Scaffold to Aid Cell-Matrix Penetration for Urologic Tissue Engineering
,”
Biomaterials
0142-9612,
30
, pp.
3865
3873
.
16.
Weaver
,
J.
, 2003, “
Electroporation of Biological Membranes From Multicellular to Nano Scales
,”
IEEE Trans. Dielectr. Electr. Insul.
1070-9878,
10
(
5
), pp.
754
768
.
17.
Lee
,
R.
, 2005, “
Cell Injury by Electric Forces
,”
Ann. N.Y. Acad. Sci.
0077-8923,
1066
, pp.
85
91
.
18.
Lee
,
R.
, and
Kolodney
,
M.
, 1987, “
Electrical Injury Mechanisms: Electrical Breakdown of Cell Membranes
,”
Plast. Reconstr. Surg.
0032-1052,
80
(
5
), pp.
672
679
.
19.
Davalos
,
R.
,
Mir
,
L.
, and
Rubinsky
,
B.
, 2005, “
Tissue Ablation With Irreversible Electroporation
,”
Ann. Biomed. Eng.
0090-6964,
33
(
2
), pp.
223
231
.
20.
Lavee
,
J.
,
Onik
,
G.
,
Mikus
,
P.
, and
Rubinsky
,
B.
, 2007, “
A Novel Nonthermal Energy Source for Surgical Epicardial Atrial Ablation: Irreversible Electroporation
,”
Heart Surg. Forum
,
10
(
2
), pp.
E162
E167
.
21.
Maor
,
E.
,
Ivorra
,
A.
,
Leor
,
J.
, and
Rubinsky
,
B.
, 2008, “
Irreversible Electroporation Attenuates Neointimal Formation After Angioplasty
,”
IEEE Trans. Biomed. Eng.
0018-9294,
55
(
9
), pp.
2268
2274
.
22.
Maor
,
E.
,
Ivorra
,
A.
,
Leor
,
J.
, and
Rubinsky
,
B.
, 2007, “
The Effect of Irreversible Electroporation on Blood Vessels
,”
Technol. Cancer Res. Treat.
1533-0346,
6
(
4
), pp.
1
6
.
23.
Rubinsky
,
B.
, 2007, “
Irreversible Electroporation in Medicine
,”
Technol. Cancer Res. Treat.
1533-0346,
6
(
4
), pp.
255
259
.
24.
Maor
,
E.
,
Ivorra
,
A.
, and
Rubinsky
,
B.
, 2009, “
Non Thermal Irreversible Electroporation: Novel Technology for Vascular Smooth Muscle Cells Ablation
,”
PLoS ONE
1932-6203,
4
(
3
), p.
e4757
.
25.
Rubinsky
,
B.
,
Onik
,
G.
, and
Mikus
,
P.
, 2007, “
Irreversible Electroporation: A New Ablation Modality—Clinical Implications
,”
Technol. Cancer Res. Treat.
1533-0346,
6
(
1
), pp.
37
48
.
26.
Al-Sakere
,
B.
,
André
,
F.
,
Bernat
,
C.
,
Connault
,
E.
,
Opolon
,
P.
,
Davalos
,
R. V.
,
Rubinsky
,
B.
, and
Mir
,
L. M.
, 2007, “
Tumor Ablation With Irreversible Electroporation
,”
PLoS ONE
1932-6203,
2
(
11
), p.
e1135
.
27.
Phillips
,
M.
,
Maor
,
E.
, and
Rubinsky
,
B.
, “
Principles of Tissue Engineering With Non-Thermal Irreversible Electroporation
,”
ASME J. Heat Transfer
0022-1481, accepted March 19, 2010.
28.
Davalos
,
R.
,
Rubinsky
,
B.
, and
Mir
,
L.
, 2003, “
Theoretical Analysis of the Thermal Effects During In Vivo Tissue Electroporation
,”
Bioelectrochemistry
1567-5394,
61
, pp.
99
107
.
29.
Tropea
,
B.
, and
Lee
,
R.
, 1992, “
Thermal Injury Kinetics in Electrical Trauma
,”
ASME J. Biomech. Eng.
0148-0731,
114
, pp.
241
250
.
30.
Dickson
,
J.
, and
Calderwood
,
S.
, 1980, “
Temperature Range and Selective Sensitivity of Tumors to Hyperthermia: A Critical Review
,”
Ann. N.Y. Acad. Sci.
0077-8923,
335
, pp.
180
205
.
31.
Lee
,
R.
, 1991, “
Physical Mechanics of Tissue Injury in Electrical Trauma
,”
IEEE Trans. Educ.
0018-9359,
34
(
3
), pp.
223
230
.
32.
Chang
,
I.
, and
Nguyen
,
U.
, 2004, “
Thermal Modeling of Lesion Growth With Radiofrequency Ablation Devices
,”
Biomed. Eng. Online
1475-925X,
3
(
27
), pp.
1
19
.
33.
Agah
,
R.
,
Pearce
,
J.
,
Welch
,
A.
, and
Motamedi
,
M.
, 1994, “
Rate Process Model for Arterial Tissue Thermal Damage: Implications on Vessel Photocoagulation
,”
Lasers Surg. Med.
0196-8092,
15
, pp.
176
184
.
34.
Orgill
,
D.
,
Solari
,
M.
,
Barlow
,
M.
, and
O’Connor
,
N.
, 1998, “
A Finite-Element Model Predicts Thermal Damage in Cutaneous Contact Burns
,”
J. Burn Care Rehabil.
0273-8481,
19
(
3
), pp.
203
209
.
35.
Lee
,
R.
, and
Astumian
,
R.
, 1996, “
The Physicochemical Basis for Thermal and Non-Thermal ‘Burn’ Injuries
,”
Burns
0305-4179,
22
(
7
), pp.
509
519
.
36.
Maor
,
E.
, and
Rubinsky
,
B.
, 2010, “
Endovascular Non-Thermal Irreversible Electroporation: A Finite Element Analysis
,”
ASME J. Biomech. Eng.
0148-0731,
132
(
3
), p.
031008
.
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