Background and study aims: We studied the ability of a photocrosslinkable chitosan in DMEM/F12 medium to maintain
submucosal thickness and to reduce bleeding after mucosal resection. We also investigated
the behavior of chitosan hydrogels with regard to wound healing
Methods: The gastric submucosal layer of heparinized rats was injected with the photocrosslinkable
chitosan in medium (which was then irradiated with ultraviolet light to form a hydrogel),
or with sodium hyaluronate, or hypertonic saline, and three investigations were done,
using three different sets of rats. The first and second were measurement of the thickness
of the layer, and of the amount of bleeding induced by mucosal resection, respectively.
Thirdly, the effects of the chitosan hydrogel on wound healing were examined histologically.
Results: Gastric submucosal layers of chitosan hydrogel-treated animals remained significantly
thicker than those of other groups for at least 6 h after injection. The total amount
of bleeding 20 min after mechanical mucosal resection was 170.0 ± 20.0 mg, 678.3 ±
226.3 mg, and 1020.0 ± 104.1 mg in the chitosan hydrogel, sodium hyaluronate, and
hypertonic saline groups, respectively. Histological study revealed that the focus
of bleeding was surrounded by chitosan hydrogel and that almost all the hydrogel was
biodegraded within 4 weeks. Furthermore, a discernible, but not statistically significant
effect of the chitosan hydrogel on wound healing was observed.
Conclusions: The chitosan hydrogel produced mucosal elevation after submucosal injection with
ultraviolet irradiation, and it significantly reduced bleeding after mucosal resection.
Our newly developed chitosan hydrogel in medium might be a promising submucosal agent
for endoscopic mucosal resection.
References
- 1
Inoue H.
Endoscopic mucosal resection for the entire gastrointestinal mucosal lesions.
Gastrointest Endosc Clin N Am.
2001;
11
459-478
- 2
Takekoshi T, Baba Y, Ota H. et al .
Endoscopic resection of early gastric carcinoma: results of a retrospective analysis
of 308 cases.
Endoscopy.
1994;
26
352-358
- 3
Inoue H, Takeshita K, Hori H. et al .
Endoscopic mucosal resection with a cap-fitted panendoscope for esophagus, stomach,
and colon mucosal lesions.
Gastrointest Endosc.
1993;
39
58-62
- 4
Ono H, Kondo H, Gotoda T. et al .
Endoscopic mucosal resection for treatment of early gastric cancer.
Gut.
2001;
48
225-229
- 5
Inoue H, Kawano T, Tani M. et al .
Endoscopic mucosal resection using a cap: techniques for use and preventing perforation.
Can J Gastroentrol.
1999;
13
477-480
- 6
Kudo S, Tamegai Y, Yamano H. et al .
Endoscopic mucosal resection of the colon: the Japanese technique.
Gastrointest Endosc Clin N Am.
2001;
11
519-535
- 7
Hirano M, Masuda K, Asanuma T. et al .
Endoscopic resection of early gastric cancer and other tumors with local injection
of hypertonic saline-epinephrine.
Gastrointest Endosc.
1988;
34
264-269
- 8
Makuuchi H, Mitomi T, Machimura T. et al .
Endoscopic mucosal resection for early esophargeal cancer by EEMR-tube method.
Stomach Intest.
1988;
28
153-159
- 9
Tada M, Inoue H, Yabata E. et al .
Colonoscopic mucosal resection using a transparent cap-fitted endoscope.
Gastroentest Endosc.
1996;
44
63-65
- 10
Suzuki H.
Endoscopic mucosal resection using ligating device for early gastric cancer.
Gastrointest Endosc Clin N Am.
2001;
11
511-518
- 11
Yamamoto H, Yube T, Isoda N. et al .
A novel method of endoscopic mucosal resection using sodium hyaluronate.
Gastrointest Endosc.
1999;
50
251-256
- 12
Yamamoto H, Koiwai H, Yube T. et al .
A successful single-step endoscopic resection of a 40 millimeter flat-elevated tumor
in the rectum: endoscopic mucosal resection using sodium hyaluronate.
Gastrointest Endosc.
1999;
50
701-704
- 13
Yamamoto H, Kawata H, Sunada K. et al .
Successful en bloc resection of large superficial tumors in the stomach and colon
using sodium hyaluronate and small-caliber-tip transparent hood.
Endoscopy.
2003;
35
690-694
- 14
Feitoza A B, Gostout C J, Burgart L J. et al .
Hydroxypropyl methylcellulose: a better submucosal fluid cushion for endoscopic mucosal
resection.
Gastrointest Endosc.
2003;
57
41-47
- 15
Shigemasa Y, Minami S.
Application of chitin and chitosan for biomaterials.
Biotechnol Gen Eng Rev.
1995;
13
383-420
- 16
Fukasawa M, Abe H, Masaoka T. et al .
The hemostatic effect of deacetylated chitin membrane on peritoneal injury in rabbit
model.
Surg Today.
1992;
22
333-338
- 17
No H K, Park N Y, Lee S H. et al .
Antibacterial activity of chitosans and chitosan oligomers with different molecular
weights.
Int J Food Microbiol.
2002;
74
7465-7472
- 18
Ishihara M, Nakanishi K, Ono K. et al .
Photocrosslinkable chitosan as a dressing for wound occlusion and accelerator in healing
process.
Biomaterials.
2002;
23
833-840
- 19
Ishihara M, Ono K, Sato M. et al .
Acceleration of wound contraction and healing with a photocrosslinkable chitosan hydrogel.
Wound Rep Regen.
2001;
9
513-521
- 20
Ueno H, Yamada H, Tanaka I. et al .
Accelerating effects of chitosan for healing at early phase of experimental open wound
in dogs.
Biomaterials.
1999;
20
1407-1414
- 21
Ono K, Saito Y, Yura H. et al .
Photocrosslinkable chitosan as a biological adhesive.
J Biomed Mater Res.
2000;
49
289-295
- 22
Ono K, Ishihara M, Ozeki Y. et al .
Experimental evaluation of photocrosslinkable chitosan as a biologic adhesive with
surgical applications.
Surgery.
2001;
130
844-850
- 23
Ito M, Ban A, Ishihara M.
Anti-ulcer effects of chitin and chitosan, healthy foods, in rats.
Jpn J Pharmacol.
2000;
82
218-225
M. Ishihara, PhD
Research Institute, National Defense Medical College
3-2 Namiki
Tokorozawa, Saitama
359-8513 Japan
Fax: +81-429-911611
eMail: ishihara@ndmc.ac.jp