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Effect of BMP-12, TGF-β1 and autologous conditioned serum on growth factor expression in Achilles tendon healing



Achilles tendon ruptures are devastating and recover slowly and incompletely. There is a great demand for biomolecular therapies to improve recovery, yet little is understood about growth factors in a healing tendon. Here, the role of growth factors during tendon healing in a rat model and their reaction to single and multiple growth factor treatment are explored.


Rat tendons were transected surgically and resutured. The expression of bFGF, BMP-12, VEGF and TGF-β1 was assessed by immunohistochemical analysis one to 8 weeks after surgery. Paracrine effects of TGF-β1 or BMP-12 added by adenoviral transfer, as well as the effect of autologous conditioned serum (ACS) on growth factor expression, were evaluated.


bFGF, BMP-12 and VEGF expression was highest 1 week after transection. bFGF and BMP-12 declined during the remaining period whereas VEGF expression persisted. TGF-β1 expression dramatically increased after 8 weeks. ACS treatment increased bFGF (P = 0.007) and BMP-12 (P = 0.004) expression significantly after 8 weeks. Also overall expression of bFGF, BMP-12 and TGF-β1 regardless of time point was significantly greater than controls with ACS treatment (P < 0.05). Both BMP-12 and TGF-β1 treatments had no significant effect. No effect was observed in VEGF with any treatment.


bFGF, BMP-12, VEGF and TGF-β1 are differentially expressed during tendon healing. Additional BMP-12 or TGF-β1 has no significant influence, whereas ACS generally increases expression of all factors except VEGF. Staged application of multiple growth factors may be the most promising biomolecular treatment.

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Autologous conditioned serum


Basic fibroblast growth factor, a.k.a. FGF-2


Bone morphogenic protein


Cartilage-derived morphogenic protein


Growth and differentiation factor


Insulin-like growth factor 1


Platelet-derived growth factor


Transforming growth factor beta 1


Vascular endothelial growth factor


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Correspondence to Martin Majewski.

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Patricia E. Heisterbach and Atanas Todorov are equally contributing first authors.

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Heisterbach, P.E., Todorov, A., Flückiger, R. et al. Effect of BMP-12, TGF-β1 and autologous conditioned serum on growth factor expression in Achilles tendon healing. Knee Surg Sports Traumatol Arthrosc 20, 1907–1914 (2012).

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  • Growth factors
  • Tendon healing
  • Biological repair
  • Animal model