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Commentary and Perspective   |    
Commentary on an article by Stavros Thomopoulos, PhD, et al.: “The Effects of Exogenous Basic Fibroblast Growth Factor on Intrasynovial Flexor Tendon Healing in a Canine Model”
Leon S. Benson, MD1
1 Illinois Bone and Joint Institute, Glenview, Illinois
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The author did not receive any outside funding or grants in support of his research for or preparation of this work. He, or a member of his immediate family, received, in any one year, payments or other benefits of less than $10,000 or a commitment or agreement to provide such benefits from commercial entities (Trimed and Accumed).

Copyright © 2010 by The Journal of Bone and Joint Surgery, Inc.
J Bone Joint Surg Am, 2010 Oct 06;92(13):e21 1-2. doi: 10.2106/JBJS.J.00939
The main article is available here
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The goal of this study was to determine whether or not there is an improvement in the healing of flexor tendon repairs by exposing the repair site to basic fibroblast growth factor (bFGF). The study involved a canine model in which intrasynovial flexor tendons were experimentally transected, exposed to a dose of bFGF, and then repaired with suture. Three tendon groups were studied: a group exposed to a lower dose of bFGF (500 ng), a group exposed to a higher dose of bFGF (1000 ng), and a control group of tendon repairs, which were exposed to no bFGF. The bFGF was delivered by implanting within the tendon repair site a fibrin matrix that contained a heparin-based delivery system capable of delivering bFGF in a controlled manner over a ten-day period. Examination of the flexor tendon repair sites after twenty-one days was performed both with histological and mechanical analysis. The investigators found that the lower dose of bFGF (500 ng) created an observable increase in biologic activity at the repair site but that the effect was too small to have any effect on the mechanical strength of repair. The higher dose of bFGF (1000 ng) had a marked increase in biologic activity at the repair site, but also did not produce any improvement of repair strength. Furthermore, the higher dose of bFGF actually caused a reduction in digital range of motion due to increased adhesions between the repaired tendon and the intrasynovial sheath.
This article is noteworthy because it is a well-designed basic-science project that investigates a common clinical problem: flexor tendon repair in an intrasynovial zone. Even though there is a high level of experimental sophistication, the project's overall construction is simple to understand and has suitable controls. The authors have presented their project in a well-written and efficiently organized manuscript that has a thoughtful and clear discussion of their results.
Aside from basic-science considerations, this project is noteworthy because it explores answers to a topic in hand surgery that has been the subject of a historic quest. Despite advances in suture technology, improved understanding of tendon biology, and increased reliance on graduated rehabilitation protocols, zone-II flexor tendon repair continues to be problematic1. The final functional result is often unpredictable, and even experienced hand surgeons recognize that the desired postoperative course lies somewhere between tendon rupture and adhesion-related stiffness. A flexor tendon repair that is strong enough to tolerate unrestricted active motion is the ideal. Despite six decades of research, we are still not there. This study, though, is one more step in the right direction. Perhaps growth factors will ultimately make the difference by supplementing the strength of suture repair enough so that motion can be tolerated and adhesions will be unlikely to form. While the results of this study suggest that the higher dose of bFGF produces an indiscriminate increase in collagen formation (and thereby adds to adhesion formation), this project nonetheless is important because it brings us one step closer toward understanding a classic dilemma in hand surgery that has not been satisfactorily resolved since the term "no-man's land" was first coined.
As a final note, this paper is valuable also because it provides insight into how scientific advances are made. These authors have painstakingly refined a canine model in which the results of flexor tendon surgery can be accurately tested. They also have developed a heparin-based delivery system through which precise amounts of growth factors can be delivered2-4. This project highlights the fact that scientific achievement usually occurs through the accumulation of information that is derived incrementally, from methodical and tedious groundwork. Small adjustments of project design, in a trial-and-error fashion, often yield great clinical advances, but discipline is required, both in the form of patience and in the form of careful attention to experimental detail. This manuscript embodies all of these elements: meticulous project design, careful testing of an animal model, validation of a biologic delivery system, and appropriate use of controls. While the effect of bFGF on intrasynovial adhesions may be disappointing, the authors have demonstrated the reliability of an in vivo flexor tendon repair model and a growth-factor delivery system that will undoubtedly be part of the "answer," whenever the answer to zone-II flexor tendon repair is finally crystallized.
Strickland  JW. Development of flexor tendon surgery: twenty-five years of progress. J Hand Surg Am.  2000;25:214-35.[PubMed][CrossRef]
 
Gelberman  RH;  Thomopoulos  S;  Sakiyama-Elbert  SE;  Das  R;  Silva  MJ. The early effects of sustained platelet-derived growth factor administration on the functional and structural properties of repaired intrasynovial flexor tendons: an in vivo biomechanic study at 3 weeks in canines. J Hand Surg Am.  2007;32:373-9.[PubMed]
 
Sakiyama-Elbert  SE;  Das  R;  Gelberman  RH;  Harwood  F;  Amiel  D;  Thomopoulos  S. Controlled-release kinetics and biologic activity of platelet-derived growth factor-BB for use in flexor tendon repair. J Hand Surg Am.  2008;33:1548-57.[PubMed]
 
Thomopoulos  S;  Harwood  FL;  Silva  MJ;  Amiel  D;  Gelberman  RH. Effect of several growth factors on canine flexor tendon fibroblast proliferation and collagen synthesis in vitro. J Hand Surg Am.  2005;30:441-7.[PubMed]
 

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References

Strickland  JW. Development of flexor tendon surgery: twenty-five years of progress. J Hand Surg Am.  2000;25:214-35.[PubMed][CrossRef]
 
Gelberman  RH;  Thomopoulos  S;  Sakiyama-Elbert  SE;  Das  R;  Silva  MJ. The early effects of sustained platelet-derived growth factor administration on the functional and structural properties of repaired intrasynovial flexor tendons: an in vivo biomechanic study at 3 weeks in canines. J Hand Surg Am.  2007;32:373-9.[PubMed]
 
Sakiyama-Elbert  SE;  Das  R;  Gelberman  RH;  Harwood  F;  Amiel  D;  Thomopoulos  S. Controlled-release kinetics and biologic activity of platelet-derived growth factor-BB for use in flexor tendon repair. J Hand Surg Am.  2008;33:1548-57.[PubMed]
 
Thomopoulos  S;  Harwood  FL;  Silva  MJ;  Amiel  D;  Gelberman  RH. Effect of several growth factors on canine flexor tendon fibroblast proliferation and collagen synthesis in vitro. J Hand Surg Am.  2005;30:441-7.[PubMed]
 
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