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PURPOSE
Pediatric craniofacial reconstruction is complicated by a limited supply of bone. Promising regenerative strategies have come in the form of BMP-2-generated endochondral bone. Most calvarial bone, however, is intramembranous in origin. We hypothesize that by leveraging bioprinting technologies to deposit precise doses of proteins known to play a key role in intramembranous ossification, we can favor intramembranous rather than endochondral osteogenesis while using lower (safer) doses of powerful morphogens.
METHODS
Five mm calvarial defects were trephinated in a mature murine model (N=8 per treatment) and filled with a bioprinted acellular dermal matrix (ADM) disc. Each half of each ADM disc was bio-printed with 1 of 4 combinations of varying doses of BMP-2 and TFG-B1. After 4 weeks, animals were sacrificed and the calvarial defects were subjected to radiographic analysis and histology.
RESULTS
The two treatment groups with less than 50 overprints of BMP-2 demonstrated less than 20% osteogenesis on radiographic evaluation. In contrast, both treatment groups with 50 overprints of BMP-2 demonstrated over 75% osteogenesis. Histology showed that the addition of TGF-B1 to BMP-2 yielded a more robust lamellar ossification pattern than that generated in response to BMP-2 alone.
CONCLUSIONS
BMP-2 confers a clear osteogenic advantage at 50 overprints. TGF-B1 seems to affect the quality of the bone generated: bone generated in response to 50 overprints of BMP-2 and 30 overprints of TGF-B1 appeared more compact, lamellar, and indeed more mature at 4 weeks than that generated in response to 50 overprints of BMP-2 and no TGF-B1. These findings may imply that TGF-B1 accelerates or enhances BMP-2-mediated osteogenesis. Specialized histology is underway to determine if the improved osteogenesis noted with TGF-B1 is associated with an intramembranous osteogenic pathway.