Volume 26, Issue 9 , Page 1144, September 2010
Growth Factor Confusion
Article Outline
To the Editor:
I have read with interest several articles in the Journal concerning the use of biologics to enhance ligament and tendon healing.1, 2, 3, 4 Clearly, the use of growth factors is at the forefront of orthopaedic research and is becoming much more prevalent. Like many orthopaedic surgeons, I am excited about the potential that these growth factors and cytokines may offer our patients, but there are several issues that must be addressed before they are clinically applicable.
Issues of manufacturing, efficacy, safety, dosing, method of administration, and regulatory pathways are all potential hurdles between animal studies and pilot studies in human beings. Furthermore, several growth factors play critical roles in the healing cascade, so it is important that studies are clear about which cytokines are being studied and how these products are processed and supplied.
All of the studies that I reference below relate to the use of autologous blood products such as platelet-rich plasma (PRP). I am concerned that readers may be confused about what “factors” are actually being applied in these studies. It is well documented that PRP contains limited amounts of a variety of growth factors—platelet-derived growth factor (PDGF), vascular endothelial growth factor, and bone morphogenetic protein for example. It is important that readers be mindful that recombinant analogs of these proteins also exist and have been used in similar fashion. It is critical when interpreting the literature to determine what exactly is being used to improve outcomes.
In their article entitled “Has Platelet-Rich Plasma Any Role in Anterior Cruciate Ligament Allograft Healing?” Nin et al.1 purport to evaluate the clinical and inflammatory parameters with the addition of PDGF in anterior cruciate ligament reconstruction with allograft. At one point, the authors acknowledge that there are several components to PRP, of which PDGF is only one. However, they spend the rest of the introduction and discussion sections focusing solely on PDGF. In my opinion, the authors make an unacceptable transition from using the term “platelet-rich plasma” in the title to discussing the results of the study solely in the context of PDGF.
Though less flagrant than Nin et al.,1 Radice et al.3—in their article entitled “Comparison of Magnetic Resonance Imaging Findings in Anterior Cruciate Ligament Grafts With and Without Autologous Platelet-Derived Growth Factors”—use less-than-clear language that may make a reader think they are discussing the growth factor PDGF in isolation as opposed to the group of factors contained in PRP. At one point in the discussion, the authors conclude that “the current application of autologous PDGFs does not allow us to specifically isolate the factors related to the process.” The references in this sentence are articles that focus on PRP, vascular endothelial growth factor, hepatocyte growth factor, epidermal growth factor, and transforming growth factor-β.3 However, if the reader does not cross-reference these citations, he or she could easily think that the conclusion focuses solely on PDGF as a growth factor.
Another example stems from a recent letter to the editor in which Vogrin et al.4 comment on an article by Orrego et al.2 entitled “Effects of Platelet Concentrate and a Bone Plug on the Healing of Hamstring Tendons in a Bone Tunnel.” Although Orrego et al. do not mention PDGF, Vogrin et al. use the term repeatedly in their critiques and recommendations.
I think the previously mentioned articles were very good studies. Moving forward, however, as more studies on biologics are published, authors, reviewers, and publishers need to be very clear about what is being studied so that appropriate comparisons can be made and conclusions can be drawn.
References
- Has platelet-rich plasma any role in anterior cruciate ligament allograft healing?. Arthroscopy. 2009;25:1206–1213
- Effects of platelet concentrate and a bone plug on the healing of hamstring tendons in a bone tunnel. Arthroscopy. 2008;24:1373–1380
- Comparison of magnetic resonance imaging findings in anterior cruciate ligament grafts with and without autologous platelet-derived growth factors. Arthroscopy. 2010;26:50–57
- . Concerns about the effects of platelet concentrate. Arthroscopy. 2009;25:941–942(letter)
PII: S0749-8063(10)00628-6
doi:10.1016/j.arthro.2010.06.020
© 2010 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.
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Volume 26, Issue 9 , Page 1144, September 2010