The controlled release of basic fibroblast growth factor promotes a rapid healing of pancreaticojejunal anastomosis with potent angiogenesis and accelerates apoptosis in granulation tissue.
BACKGROUND
Our previous study demonstrated that bFGF-GH promoted healing of the pancreaticojejunostomy (PJ) in an animal model. We examined the healing process in detail to investigate the significance of treatment with basic fibroblast growth factor (bFGF) incorporated in gelatin hydrogel (GH) microspheres for anastomotic healing.


METHODS
The optimal dose of bFGF was determined by administering bFGF concentrations of 1, 10, and 100 μg in six beagle dogs and assessing the results on d 7. Next, 28 dogs received a jejunal subserosal injection of 10 μg bFGF-GH or GH alone. The healing process was sequentially analyzed on d 4, 7, 21, and 28. The following types of assessment were performed: breaking strength test, pathologic examination, and calculations of collagen content, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) index, and microvessel density (MVD).


RESULTS
The administration of a bFGF dose of more than 10 μg induced a significantly higher breaking strength and more abundant granulation tissues. Histologic observations of the bFGF-GH group on d 7 and the GH-alone group on d 21 revealed abundant granulation tissue with migrating fibroblasts, inflammatory cells, and capillaries. Marked neovascularization and dense collagen deposition were detected in both groups on d 28. The collagen content and breaking strength did not significantly differ between both groups on d 28. A significantly higher TUNEL index and a rapid decline in the number of vimentin-positive cells were detected in the bFGF-GH group from d 21 onward. The MVD in the bFGF-GH group was significantly higher from d 7 onward


CONCLUSIONS
Basic FGF-GH administration can promote the rapid completion of PJ anastomosis and may help improve the quality of the healing of granulation tissue by conferring potent angiogenesis and accelerating apoptosis.
Katsuno
Akira
A
Department of Surgery, Nippon Medical School, Tokyo, Japan.
Aimoto
Takayuki
T
Uchida
Eiji
E
Tabata
Yasuhiko
Y
Miyamoto
Masaaki
M
Tajiri
Takashi
T
D000714:Anastomosis, Surgical; D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage / Q000494:pharmacology*; D006097:Granulation Tissue / Q000473:pathology*; D020100:Hydrogels; D007583:Jejunum / Q000601:surgery*; D008863:Microspheres; D055806:Microvessels / Q000187:drug effects; D023421:Models, Animal; D018919:Neovascularization, Physiologic / Q000187:drug effects* / Q000502:physiology; D010179:Pancreas / Q000601:surgery*; D014945:Wound Healing / Q000187:drug effects* / Q000502:physiology
D020100:Hydrogels; D016222:Fibroblast Growth Factor 2