Recombinant Basic Fibroblast Growth Factor Stimulates Wound Healing in Healing-impaired dbldb Mice

The stimulatory effect of recombinant basic fibroblast growth factor (bFGF) on wound healing was assessed using healing-impaired (db/db) mice. Full-thickness wounds were made in female diabetic C57BL/Ksj AM mice, and their normal (db/+) littermates with a punch biopsy instrument . Recombinant bFGF was applied locally to the open wound once a day. The mice were later killed and histological sections of the wounds were prepared . The degree of wound healing was evaluated using several histological parameters such as degree of reepithelialization, granulation tissue thickness, matrix density, number of infiltrated cells, and number ofcapillaries . Wounds from normal mice displayed good reepithelialization rates and granulation tissue formation, while wounds from db/db mice had poor responses, especially in the dermal parameters . Although the application of bFGF to wounds in the normal (db/+ ) mice had little effect, application of bFGF to wounds in AM mice induced significant responses in all of the dermal parameters compared with nontreated AM mice (p < 0.001) . In the presence of bFGF, these parameters approximated those observed in nontreated littermates. A minimum of 0.5 wg bFGF in either single or multiple applications was required for a significant effect . bFGF that was either boiled or pretreated with neutralizing antibody had little stimulatory effect . Time-course experiments indicated that the granulation response in bFGF-treated mice peaked between 8 and 12 d, and decreased after 12 d, while matrix density continued to increase until the 18th day (P < 0.05) . The breaking strength of healed linear wounds inAMmice was also decreased when compared with heterozygous littermates . This parameter was also improved by the administration ofbFGF to the wounds (p < 0.05) .