Purpose: The goals of this study are to assess the osteogenic potential of palatal shelf mucoperiosteum following cleft repair in a juvenile caprine model, as well as to evaluate and compare midfacial growth and palatal development following surgical repair with and without rhBMP-4 gene therapy. To accomplish these goals, rhBMP-4 gene therapy with surgical repair are compared to surgical repair only of cleft palate in a congenital caprine model. Previous work by Weinzweig et al., showed that repair in six week old goats results in palatal narrowing following repair but no partial bony palatal fusion. Our hypothesis is that rhBMP-4 gene therapy with surgical repair augments palatal bony regeneration and can lead to partial bony palatal fusion in a juvenile caprine model.
Materials and Methods: Sixteen six-week old goats were divided into five experimental groups: 1. untreated congenital cleft (negative control), 2. surgical repair without rhBMP-4 (positive control), 3. surgical repair with rhBMP-4 in polyD,L-lactide bioresorbable carrier, and 4. rhBMP-4 in PL carrier without surgical repair, and 5. surgical repair with PL carrier only. The rhBMP-4 treated animals received BMP-4 plasmid DNA to produce BMP-4 in the surrounding, resident cells. The animals were euthanized six weeks post-operatively (twelve weeks old). Quantitative data will include the determination of radiopacity within the cleft defects and histological trabecular and cortical bone formation. Qualitative data will be immunohistochemistry analyses of BMP4.
Results: The histomorphometry and radiomorphmetry measurements of the sixteen goats are currently being analyzed and will be presented. We are expecting that the group treated with rhBMP-4 gene therapy and surgical repair will have as much if not greater palatal bony fusion than the group with surgical repair only as well as greater bony formation than the other control groups. We are also expecting to be able to see the qualitative evidence of new bone formation with rhBMP-4 immunohistochemical staining.
Conclusions: We are expecting rhBMP-4 gene therapy with surgical repair to be at least equivalent and potentially superior in palatal bony formation when compared to surgical repair only, in a cleft palate juvenile caprine model, which mimics more closely the pediatric patient population with cleft palate. Given these findings, rhBMP-4 gene therapy may provide both an adjunct and alternative to autografting in the cleft palate patient, decreasing both the morbidity and costs associated with autografting.