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Adeno-Associated Virus-2-Mediated bFGF Gene Transfer to Digital Flexor Tendons Significantly Increases Healing Strength

An in Vivo Study

¹ Department of Hand Surgery, Hand Surgery Research Center, Affiliated Hospital of Nantong University, 20 West Temple Road, Nantong 226001, Jiangsu, China. E-mail address for J.B. Tang: jinbotang{at}yahoo.com
² Department of Surgery, Roger Williams Medical Center, Boston University School of Medicine, 825 Chalkstone Avenue, Providence, RI 02908
Investigation performed at the Department of Hand Surgery, Nantong University, Nantong, China, and the Department of Surgery, Roger Williams Medical Center, Boston University School of Medicine, Providence, Rhode Island

Disclosure: In support of their research for or preparation of this work, one or more of the authors received, in any one year, outside funding or grants in excess of $10,000 from the Health Bureau of Jiangsu Province, Natural Science Foundation, and Department Fund of the Affiliated Hospital of Nantong University. Neither they nor a member of their immediate families received payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity. No commercial entity paid or directed, or agreed to pay or direct, any benefits to any research fund, foundation, division, center, clinical practice, or other charitable or nonprofit organization with which the authors, or a member of their immediate families, are affiliated or associated.

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 10⁹ 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.

Clinical Relevance: Novel molecular approaches, such as those described in the present study, hold great promise to enhance the biological healing potential of the disrupted and repaired intrasynovial flexor tendon.

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