Spatial regulation of gene expression in nonsyndromic sagittal craniosynostosis.

OBJECTIVECranial suture patterning and development are highly regulated processes that are not entirely understood. While studies have investigated the differential gene expression for different sutures, little is known about gene expression changes during suture fusion. The aim of this study was to examine gene expression in patent, fusing, and fused regions along sagittal suture specimens in nonsyndromic craniosynostosis patients.METHODSSagittal sutures were collected from 7 patients (average age 4.5 months) who underwent minimally invasive craniotomies at the Children's Hospital of Richmond at VCU under IRB approval. The sutures were analyzed using micro-CT to evaluate patency. The areas were classified as open, fusing, or fused and were harvested, and mRNA was isolated. Gene expression for bone-related proteins, osteogenic and angiogenic factors, transforming growth factor-ß (TGF-ß) superfamily, and Wnt signaling was analyzed using quantitative polymerase chain reaction and compared with normal sutures collected from fetal demise tissue (control).RESULTSMicro-CT demonstrated that there are variable areas of closure along the length of the sagittal suture. When comparing control samples to surgical samples, there was a significant difference in genes for Wnt signaling, TGF-ß, angiogenic and osteogenic factors, bone remodeling, and nuclear rigidity in mRNA isolated from the fusing and fused areas of the sagittal suture compared with patent areas (p < 0.05).CONCLUSIONSIn nonsyndromic sagittal craniosynostosis, the affected suture has variable areas of being open, fusing, and fused. These specific areas have different mRNA expression. The results suggest that BMP-2, FGFR3, and several other signaling pathways play a significant role in the regulation of suture fusion as well as in the maintenance of patency in the normal suture.

Electrospinning of PEGylated polyamidoamine dendrimer fibers.

Polyamidoamine (PAMAM) dendrimers have emerged as an important class of nanostructured materials and have found a broad range of applications. There is also an ongoing effort to synthesize higher-complexity structures using PAMAM dendrimers as enabling building blocks. Herein, we report for the first time the fabrication of electrospun nanocomposite fibers composed of dendrimer derivatives, namely PEGylated PAMAM dendrimers, blended with a small amount of high-molecular-weight polyethylene oxide (PEO). Morphological features and mechanical properties of the resulting dendrimer fiber mats were assessed.