Genomewide Molecular and Biologic Characterization of Biomembrane Formation Adjacent to a Methacrylate Spacer in the Rat Femoral Segmental Defect Model

Objectives: This study focuses upon the morphologic and molecular features of the layer of cells, termed the “biomembrane,” which forms around methacrylate spacers in bone segmental defects. The objective of this research was to assess the biomembrane formed in a novel rodent femoral segmental defect model at 4, 8, and 16 weeks with histologic and molecular studies. Methods: Following Institutional Animal Care and Use Committee approval, a segmental defect was created in the rat femur and stabilized with the AO LockingRatNail and analyzed at 4, 8, and 16 weeks postsurgery using digital radiologic imaging, morphological and immunohistochemical studies, and genomewide gene expression studies employing microarray analysis. Results: The biomembrane formed around the methacrylate spacer was rich in vasculature, which showed vascular endothelial growth factor immunolocalization. The biomembrane supported development of foci of bone and cartilage within it. Bone morphogenetic protein 2 immunolocalization and gene expression were positive within developing osseous and chondrocyte foci. Microarray analysis showed significant expression of key genes related to bone and cartilage formation and angiogenesis. Conclusions: This rat bone model was effective in creation of the biomembrane. Bone and cartilage foci were formed within the vascularized biomembrane with associated expression of genes critical for bone and cartilage development/formation and vascularization. The polymethyl methacrylate–induced biomembrane offers an exciting potential solution for segmental defects; the biomembrane, may act as a receptive bed and also serve as a source for mesenchymal stem cells, which could be recruited/directed for the healing process.