Synergistic Effects of FGF-2 and BMP-7 in Bone Regeneration for Alveolar Clefts
Doepker, Mikayla J.
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Cleft palate is the most common congenital craniofacial birth defect and occurs by the improper fusion of the palatal shelves during the sixth week of gestation. Among cleft palate patients, 75% also present with alveolar bone defects. The gold standard treatment for alveolar clefts is an iliac crest bone graft in which a piece of the hipbone is harvested and implanted into the defect site. This treatment is not ideal for the patient and is commonly associated with donor site morbidity and pain at the site of harvest. Tissue engineering is a rapidly evolving field that combines a biocompatable scaffold, multipotent cells, and applicable growth factors to create new tissue growth. Using this logic, we aimed to find a suitable treatment alternative to alveolar clefts by combining a novel nanofibrous spongy microsphere (NF-SMS), induced pluripotent mesenchymal stem cells (iMSC), and bone morphogenic protein-7 (BMP-7) coupled with fibroblast growth factor-2 (FGF-2). In this study, the optimal dosing of FGF-2 within the 0-10 ng/mL range is investigated as well as the synergistic effects of FGF-2 and BMP-7 when used in combination. The combination of NF-SMS, iMSCs, and growth factors were tested but no data was able to be collected. No clear optimal dose for FGF-2 was found, although 5 ng/mL was the most promising dose as shown through qRT-PCR, ALP activity, calcium concentration, and Alizarin Red S staining. FGF-2 and BMP-7 were found to product a synergistic effect and were most osteoinductive with combined FGF- 2/BMP-7 treatment for the first three days, followed by continuous BMP-7 treatment. These data provide a promising outlook for continued research in tissue engineering with FGF-2 and BMP-7 in hopes of developing a new therapeutic alveolar cleft treatment.