The Ambystoma maxicanum (axolotl) regenerates strikingly from wounds and amputations. Comparing its healing ability to non-regenerative species such as the mouse should help narrow in on mechanisms to improve human wound healing. Here, the tongue and intermandibular soft tissues of both mice (C57BL/6NCrl) and axolotls were wounded with a 2–2.5 mm punch biopsy. The study aimed to compare the differences between these 2 species following surgical resection with regard to the macroscopic and histological characteristics. These include wound closure times, epithelial wound sealing and thickness as well as acute immune marker myeloperoxidase (MPO) response over 30 days. Post surgery, mice visually showed greater haemorrhage; their wounds immediately collapsed while it took 14 days for the axolotls mandibular void to close. The epithelium sealed the axolotls’ wound margins within 24 h with a maximal mean thickness of 0.42 ± 0.13-fold normalized to unwounded skin. In mice, the epithelium separately sealed the ventral and dorsal sides, respectively at 7 and 7–30 days with mean maximal epithelial thicknesses reaching 13 ± 5.6 and 3.0 ± 0.63-fold. Mean MPO-positive cell values peaked in axolotls at 14 ± 1.5-fold between hours 6–12; while in mice, it peaked at 8.7 ± 0.9-fold between hours 24–96. We conclude that axolotls form smaller blood clots, have a faster and thinner epithelial cell migrating front, and a shorter MPO-positive cell response in comparison to mice. These observations may help refine future oral and facial wound-healing research and treatment.

1.
Belamarich
FA
.
Hemostasis in animals other than mammals: the role of cells
.
Prog Hemost Thromb
.
1976
;
3
:
191
209
.
2.
Bhaskar
SN
,
Lilly
GE
.
Traumatic Granuloma of the Tongue (Human and Experimental)
.
Oral Surg Oral Med Oral Pathol
.
1964
;
18
:
206
18
.
3.
Charbonneau
AM
,
Roy
S
,
Tran
SD
.
Oral-Facial Tissue Reconstruction in the Regenerative Axolotl
.
J Exp Zool B Mol Dev Evol
.
2016
;
326
(
8
):
489
502
.
4.
Denis
JF
,
Lévesque
M
,
Tran
SD
,
Camarda
AJ
,
Roy
S
.
Axolotl as a Model to Study Scarless Wound Healing in Vertebrates: Role of the Transforming Growth Factor Beta Signaling Pathway
.
Adv Wound Care (New Rochelle)
.
2013
;
2
(
5
):
250
60
.
5.
Dovi
JV
,
He
LK
,
DiPietro
LA
.
Accelerated wound closure in neutrophil-depleted mice
.
J Leukoc Biol
.
2003
;
73
(
4
):
448
55
.
6.
Dovi
JV
,
Szpaderska
AM
,
DiPietro
LA
.
Neutrophil function in the healing wound: adding insult to injury?
Thromb Haemost
.
2004
;
92
(
2
):
275
80
.
7.
Emmel
VE
.
Studies on the non-nucleated cytoplasmic elements of the blood. III. Leucoplastids or non-nucleated leucocytic derivatives in vertebrates other than mammals
.
Am J Anat
.
1925
;
35
(
1
):
31
61
.
8.
Ferretti
P
.
Re-examining jaw regeneration in urodeles: what have we learnt?
Int J Dev Biol
.
1996
;
40
(
4
):
807
11
.
9.
Fu
Y
,
Zhou
E
,
Wei
Z
,
Liang
D
,
Wang
W
,
Wang
T
,
Glycyrrhizin inhibits the inflammatory response in mouse mammary epithelial cells and a mouse mastitis model
.
FEBS J
.
2014
;
281
(
11
):
2543
57
.
10.
Godwin
JW
,
Rosenthal
N
.
Scar-free wound healing and regeneration in amphibians: Immunological influences on regenerative success
.
Differentiation
.
2014
;
87
(
1–2
):
66
75
.
11.
Godwin
JW
,
Pinto
AR
,
Rosenthal
NA
.
Macrophages are required for adult salamander limb regeneration
.
Proc Natl Acad Sci USA
.
2013
;
110
(
23
):
9415
20
.
12.
Godwin
JW
,
Pinto
AR
,
Rosenthal
NA
.
Chasing the recipe for a pro-regenerative immune system
.
Semin Cell Dev Biol
.
2017
;
61
:
71
9
.
13.
Greven
H
,
Richter
H
,
Clemen
G
.
Formation of the secondary tongue in Hynobius leechi and Ambystoma mexicanum (Amphibia: Urodela)
.
Vertebrate Zoology
.
2013
;
63
(
2
):
217
32
.
14.
Häkkinen
L
,
Larjava
H
,
Koivisto
L
.
Granulation Tissue Formation and Remodeling
. In:
Larjava
H
, editor.
Oral Wound Healing.John Wiley & Sons, Ltd.
;
2012
. p.
125
73
.
15.
Huang
TY
,
Chang
CC
,
Cheng
NC
,
Wang
MH
,
Chiou
LL
,
Lee
KL
,
Re-epithelialization of large wound in paedomorphic and metamorphic axolotls
.
J Morphol
.
2017
;
278
(
2
):
228
35
.
16.
Kawasumi
A
,
Sagawa
N
,
Hayashi
S
,
Yokoyama
H
,
Tamura
K
.
Wound Healing in Mammals and Amphibians: Toward Limb Regeneration in Mammals
. In:
Heber-Katz
E
,
Stocum
DL
, editors.
New Perspectives in Regeneration
.
Berlin, Heidelberg
:
Springer Berlin Heidelberg
;
2013
. p.
33
49
.
17.
Kozlowski
C
,
Jeet
S
,
Beyer
J
,
Guerrero
S
,
Lesch
J
,
Wang
X
,
An entirely automated method to score DSS-induced colitis in mice by digital image analysis of pathology slides
.
Dis Model Mech
.
2013
;
6
(
3
):
855
65
.
18.
Larjava
H
,
Häkkinen
L
,
Koivisto
L
.
Re-Epithelialization of Wounds
. In:
Larjava
H
, editor.
Oral Wound Healing.
John Wiley & Sons, Ltd.
;
2012
. p.
81
123
.
19.
Levesque
M
,
Villiard
E
,
Roy
S
.
Skin wound healing in axolotls: a scarless process
.
J Exp Zool B Mol Dev Evol
.
2010
;
314
(
8
):
684
97
.
20.
Lewis
JH
.
The Amphibians. Comparative Hemostasis in Vertebrates
.
Boston
:
Springer US
;
1996
. p.
71
84.
21.
Lopez
D
,
Lin
L
,
Monaghan
JR
,
Cogle
CR
,
Bova
FJ
,
Maden
M
,
Mapping hematopoiesis in a fully regenerative vertebrate: the axolotl
.
Blood
.
2014
;
124
(
8
):
1232
41
.
22.
Lorenz
HP
,
Longaker
MT
,
Perkocha
LA
,
Jennings
RW
,
Harrison
MR
,
Adzick
NS
.
Scarless wound repair: a human fetal skin model
.
Development
.
1992
;
114
(
1
):
253
9
.
23.
Mescher
AL
.
Macrophages and fibroblasts during inflammation and tissue repair in models of organ regeneration
.
Regeneration (Oxf)
.
2017
;
4
(
2
):
39
53
.
24.
Mescher
AL
,
Neff
AW
,
King
MW
.
Inflammation and immunity in organ regeneration
.
Dev Comp Immunol
.
2017
;
66
:
98
110
.
25.
Navarro Cuellar
I
,
González Otero
T
,
Ruiz Cruz
JA
,
Navarro Vila
C
.
Reconstruction of Soft Tissue Defects Using Microsurgical Flaps
.
Cham
:
Springer International Publishing
;
2015
.
26.
Oakley
C
,
Larjava
H
.
Hemostasis, Coagulation and Complications
. In:
Larjava
H
, editor.
Oral Wound Healing
.
Chichester
:
John Wiley & Sons
;
2012
. p.
11
38
.
27.
Pulli
B
,
Ali
M
,
Forghani
R
,
Schob
S
,
Hsieh
KL
,
Wojtkiewicz
G
,
Measuring myeloperoxidase activity in biological samples
.
PLoS One
.
2013
;
8
(
7
):
e67976
.
28.
Rovin
S
,
Costich
ER
,
Fleming
JE
,
Gordon
HA
.
Healing of Tongue Wounds in Germfree and Conventional Mice
.
Arch Pathol
.
1965
;
79
:
641
3
.
29.
Seifert
AW
,
Maden
M
.
New Insights into Vertebrate Skin Regeneration
. In:
Jeon
KW
, editor.
Int Rev Cell Mol Biol
Academic Press
;
2014
. p.
129
69
.
30.
Seifert
AW
,
Monaghan
JR
,
Voss
SR
,
Maden
M
.
Skin Regeneration in Adult Axolotls: A Blueprint for Scar-Free Healing in Vertebrates
.
PLoS One
.
2012
;
7
(
4
):
e32875
.
31.
Standish
SM
,
Eversole
LR
.
Regenerative changes in rat tongue muscle following crushing injury
.
Oral Surg Oral Med Oral Pathol
.
1970
;
30
(
1
):
87
98
.
32.
Sundberg
JP
,
Booth
CJ
,
Nanney
LB
,
Fleckman
P
,
King
LE
.
Skin and Adnexa
. In:
Treuting
PM
,
Dintzis
SM
,
Montine
KS
, editors.
Comparative Anatomy and Histology
.
San Diego
:
Academic Press
;
2018
. p.
511
42.
33.
Szpaderska
AM
,
Zuckerman
JD
,
DiPietro
LA
.
Differential injury responses in oral mucosal and cutaneous wounds
.
J Dent Res
.
2003
;
82
(
8
):
621
6
.
34.
Tanaka
EM
,
Reddien
PW
.
The Cellular Basis for Animal Regeneration
.
Dev Cell
.
2011
;
21
(
1
):
172
85
.
35.
Tank
PW
,
Carlson
BM
,
Connelly
TG
.
A staging system for forelimb regeneration in the axolotl, Ambystoma mexicanum
.
J Morphol
.
1976 Sep
;
150
(
1
):
117
28
.
36.
Tassava
RA
,
Garling
DJ
.
Regenerative responses in larval axolotl limbs with skin grafts over the amputation surface
.
J Exp Zool
.
1979
;
208
(
1
):
97
110
.
37.
Turabelidze
A
,
DiPietro
L
.
Inflammation and Wound Healing
. In:
Larjava
H
, editor.
Oral Wound Healing
.
Chichester
:
John Wiley & Sons
;
2012
. p.
41
2.
38.
Wong
VW
,
Sorkin
M
,
Glotzbach
JP
,
Longaker
MT
,
Gurtner
GC
.
Surgical Approaches to Create Murine Models of Human Wound Healing
.
J Biomed Biotechnol
.
2011
;
2011
:
969618
.
39.
Young
HE
,
Bailey
CF
,
Dalley
BK
.
Environmental conditions prerequisite for complete limb regeneration in the postmetamorphic adult land-phase salamander, Ambystoma
.
Anat Rec
.
1983a
;
206
(
3
):
289
94
.
40.
Young
HE
,
Bailey
CF
,
Dalley
BK
.
Gross morphological analysis of limb regeneration in postmetamorphic adult Ambystoma
.
Anat Rec
.
1983b
;
206
(
3
):
295
306
.
41.
Ziermann
JM
,
Diogo
R
.
Cranial Muscle Development in the Model Organism Ambystoma mexicanum: Implications for Tetrapod and Vertebrate Comparative and Evolutionary Morphology and Notes on Ontogeny and Phylogeny
.
Anat Rec (Hoboken)
.
2013
;
296
(
7
):
1031
48
. .
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