Ectopic Application of Recombinant BMP-2

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Ectopic Application of Recombinant BMP-2

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The bone morphogenetic protein 2 (Bmp-2) and bone morphogenetic proteins 4 (Bmp-4) are expressed in discrete regions at the distal tips of the early facial primordia suggesting possible roles for BMP-2 and BMP-4 during chick facial development. We show that expression of Bmp-4 and Bmp-2 is correlated with the expression of Msx-1 and Msx-2 and that ectopic application of BMP-2 and BMP-4 can activate Msx-1 and Msx-2 gene expression in the developing facial primordia.
 
We correlate this activation of gene expression with changes in skeletal development. For example, activation of Msx-1 gene expression across the distal tip of the mandibular primordium is associated with an extension of Fgf-4 expression in the epithelium and bifurcation of Meckel's cartilage. In the maxillary primordium, extension of the normal domain of Msx-1 gene expression is correlated with extended epithelial expression of shh and bifurcation of the palatine bone. We also show that application of BMP-2 can increase cell proliferation of the mandibular primordia. Our data suggest that BMP-2 and BMP-4 are part of a signalling cascade that controls outgrowth and patterning of the facial primordia.
 
Delayed healing is still a severe complication in the clinic. The aim of the present study was to investigate the effect of locally delivered BMP-2 incorporated in a poly(d,l-lactide) (PDLLA) implant coating in a rat model with delayed tibial healing. The healing delay in this model is not caused by mechanical instability or additional tissue manipulation and presents therefore a common and challenging clinical situation of impaired healing. Radiological, histological and biomechanical evaluations were performed at days 5, 10, 28, 42, and 84 after tibial osteotomy. The control group showed a delayed healing without complete bridging and without reaching the biomechanical stability of the contralateral tibiae after 84 days.
 
The mechanical stability of the BMP-treated tibiae showed a significant increase at days 28 and 42 compared to the control group and exceeded the stability of the intact contralateral tibiae. Less cartilage was detected at day 28 and the mineralisation was significantly enhanced at day 42 due to the local BMP application. Looking at the early healing phase (day 10) a reduced vascularisation was seen in the BMP group. This reflects the situation seen during normal healing, whereas the delayed healing in the present model had an increased vascularisation. The present study clearly demonstrates that local BMP-2 application can stimulate delayed healing in a clinically relevant animal model.

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