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Combination of growth factors found superior to single growth factor for tendon healing
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A mix of growth factors and cytokines in activated serum yields tendon healing superior to single growth factors, with growth factors BMP-12 and TGF-beta yielding better results and more favorable collagen expression ratios respectively.
Those were the results of a recent study presented by Martin Majewski, MD, at the 2010 ESSKA Conference in Oslo, Norway.
The study was reportedly designed to compare the benefits of three different approaches: TGF-beta as an example for multifunctional growth factors inducing a wide range of cellular responses, BMP-12 as an example for the specific induction of tendon and ligament tissue, and a growth factor cytokine mix derived from serum and activated platelets as an example for biological therapy.
“Going through the literature, it seems evident that there is a need for a growth factor application to enhance the healing of tendon tissue,” Majewski said. “But it is clear that there is more needed than just one single application of one factor. There needs to be a combination of various factors.”
Adding the growth factors
Majewski reported his team used a transected rat Achilles tendon for each of the three approaches. Staining intensity for BMP-12, bFGF, TGF-beta and VEGF showed all were highly expressed at early healing stages, so the researchers introduced BMP-12, cDNA and TGF-beta cDNA — as well as an activated serum — at the time of tendon surgery, as well as 24 and 48 hours postoperatively.
The rats were sacrificed 1, 2, 4 and 8 weeks postoperatively, and their Achilles tendon tendon-bone units were collected. Researchers then analyzed regenerated sections biomechanically, histochemically and immunochemically.
Better in combination
TGF-beta was found to have a “significantly increased” maximum failure load 1 week after surgery, with “significantly higher” tendon stiffness. Majewski also reported that histological examination showed a much more organized and homogeneous pattern of collagen fibers over all time points when compared to the control.
The BMP-12 group tendons showed significantly greater strength than the control at 1 week, with higher tendon stiffness at 1, 2 and 4 weeks. The histological examination was “quite similar to the TGF-beta group,” Majewski said, but after 8 weeks he did find a tendon with an enchondral ossification at the experimental group.
The activated serum tendons reached stiffness values 4 weeks earlier than controls. Majewski noted that “visibly thicker and more bundled” collagen fibers were apparent as early as the first week postoperatively, and the trend continued over time. At 8 weeks, he added, the tendons had a smooth appearance closely resembling normal tendons.
“Overall, you can see that each application of growth factors — TGF-beta, BMP-12 and serum — had its advantages in terms of biomechanics, collagen, and histological appearance,” Majewski concluded. “It might be better to add all these growth factors in combination over different time points as compared to just one injection in one day.” – by Robert Press
Reference:
- Majewski M. Improvement of tendon healing with growth factors. Paper #FP20-1381. Presented at the 2010 ESSKA Congress. June 9-12. Oslo.
- Martin Majewski, MD, can be reached at majewski01@yahoo.de.
