Experimental evaluation of photocrosslinkable chitosan as a biologic adhesive with surgical applications.
BACKGROUND
In various surgical cases, effective tissue adhesives are required for both hemostasis (eg, intraoperative bleeding) and air sealing (eg, thoracic surgery). We have designed a chitosan molecule (Az-CH-LA) that can be photocrosslinked by ultraviolet (UV) light irradiation, thereby forming a hydrogel. The purpose of this work was to evaluate the effectiveness and safety of the photocrosslinkable chitosan hydrogel as an adhesive with surgical applications.


METHODS
The sealing ability of the chitosan hydrogel, determined as a bursting pressure, was assessed with removed thoracic aorta, trachea, and lung of farm pigs and in a rabbit model. The carotid artery and lung of rabbits were punctured with a needle, and the chitosan hydrogel was applied to, respectively, stop the bleeding and the air leakage. In vivo chitosan degradability and biologic responses were histologically assessed in animal models.


RESULTS
The bursting pressure of chitosan hydrogel (30 mg/mL) and fibrin glue, respectively, was 225 +/- 25 mm Hg (mean +/- SD) and 80 +/- 20 mm Hg in the thoracic aorta; 77 +/- 29 mm Hg and 48 +/- 21 mm Hg in the trachea; and in the lung, 51 +/- 11 mm Hg (chitosan hydrogel), 62 +/- 4 mm Hg (fibrin glue, rubbing method), and 12 +/- 2 mm Hg (fibrin glue, layer method). The sealing ability of the chitosan hydrogel was stronger than that of fibrin glue. All rabbits with a carotid artery (n = 8) or lung (n = 8) that was punctured with a needle and then sealed with chitosan hydrogel survived the 1-month observation period without any bleeding or air leakage from the puncture sites. Histologic examinations demonstrated that 30 days after application, a fraction of the chitosan hydrogel was phagocytosed by macrophages, had partially degraded, and had induced the formation of fibrous tissues around the hydrogel.


CONCLUSIONS
A newly developed photocrosslinkable chitosan has demonstrated strong sealing ability and a great potential for use as an adhesive in surgical operations.
Ono
K
K
Department of Surgery II, National Defense Medical College, Saitama, Japan.
Ishihara
M
M
Ozeki
Y
Y
Deguchi
H
H
Sato
M
M
Saito
Y
Y
Yura
H
H
Sato
M
M
Kikuchi
M
M
Kurita
A
A
Maehara
T
T
D000818:Animals; D001684:Biological Dressings; D002686:Chitin / Q000031:analogs & derivatives; D048271:Chitosan; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D008168:Lung / Q000473:pathology / Q000601:surgery; D008297:Male; D011312:Pressure; D011817:Rabbits; D013552:Swine
D002686:Chitin; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D048271:Chitosan