Adeno-associated virus-2-mediated bFGF gene transfer to digital flexor tendons significantly increases healing strength. an in vivo study.
BACKGROUND
Treatment of the disrupted intrasynovial flexor tendon is troublesome and can be complicated by the rupture of weak repairs and the formation of adhesions. The central issue underlying the unsatisfactory outcomes is the lack of sufficient healing capacity, which prohibits aggressive postoperative tendon motion. Transfer of genes that are critical to healing by means of an efficient vector system offers a promising way of strengthening the repair. The purpose of the present study was to transfer the basic fibroblast growth factor gene through the adeno-associated viral-2 vector to injured digital flexor tendons and to investigate its effects on the healing strength of the tendon and on adhesion formation in a clinically relevant injury model.


METHODS
One hundred and twenty-eight long toes from sixty-four white leghorn chickens were used. The flexor digitorum profundus tendons were cut completely in the digital sheath area and were repaired with the modified Kessler method. In Group 1, a total of 2 x 10(9) particles of adeno-associated viral vector harboring the basic fibroblast growth factor gene were injected into both ends of the cut tendon. In Group 2, the same amount of adeno-associated viral vector carrying the luciferase gene was injected. In Group 3 (the non-injection control group), the tendons were sutured without any injection. At the end of two, four, eight, and twelve weeks, the toes were harvested and the tendons were tested for determination of the load-to-failure strength. At the end of eight and twelve weeks, the energy required to flex the toes was tested. The morphology regarding healing status and adhesions around the tendon were evaluated at two, four, eight, and twelve weeks.


RESULTS
The ultimate strength of repaired tendons that had been treated with adeno-associated viral vector-basic fibroblast growth factor was significantly greater than that of tendons that had been treated with the sham vector or simple repair both during the early healing period (two weeks, p < 0.01; four weeks, p < 0.01) and a later period (eight weeks, p < 0.05). At four weeks, the strength of tendons that had been treated with adeno-associated viral vector-basic fibroblast growth factor (8.9 +/- 1.9 N) was significantly greater than that of tendons that had been treated with sham vector (6.1 +/- 1.0 N) (p < 0.01) or simple suture (5.7 +/- 1.1 N) (p < 0.001). Statistically, the grading of adhesions was the same among all three groups at four and eight weeks, but at twelve weeks it was significantly less severe for tendons that had been treated with adeno-associated viral vector-basic fibroblast growth factor than for those that had been treated with simple suture (p < 0.05). The energy that was required to flex the toes after treatment with adeno-associated viral vector-basic fibroblast growth factor was not increased at eight or twelve weeks compared with that in the controls.


CONCLUSIONS
The present study demonstrates that basic fibroblast growth factor gene transfer to digital flexor tendons by means of adeno-associated viral vector-2 significantly increases healing strength during the critical tendon healing period but does not increase adhesion formation.
Tang
Jin Bo
JB
Department of Hand Surgery, Hand Surgery Research Center, Affiliated Hospital of Nantong University, 20 West Temple Road, Nantong 226001, Jiangsu, China. jinbotang@yahoo.com
Cao
Yi
Y
Zhu
Bei
B
Xin
Ke-Qin
KQ
Wang
Xiao Tian
XT
Liu
Paul Y
PY
D000818:Animals; D001696:Biomechanical Phenomena; D002645:Chickens; D000229:Dependovirus; D016222:Fibroblast Growth Factor 2 / Q000235:genetics*; D005384:Finger Joint; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D011897:Random Allocation; D013708:Tendon Injuries / Q000473:pathology / Q000601:surgery*; D013718:Tensile Strength; D000267:Tissue Adhesions; D014034:Toes; D014945:Wound Healing
D016222:Fibroblast Growth Factor 2