• Patricia E Heisterbach, Atanas Todorov, Rudolf Flückiger, Christopher H Evans, and Martin Majewski.
• Orthopädische Klinik, Behandlungszentrum Bewegungsapparat, Universität Basel, Spitalstrasse 21, 4031, Basel, Switzerland.
• Knee Surg Sports Traumatol Arthrosc. 2012 Oct 1;20(10):1907-14.

PurposeAchilles 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.MethodsRat 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.ResultsbFGF, 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.ConclusionbFGF, 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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