Silicon Ions May Fill Soft Tissue Defects by Inducing Adipogenesis and Angiogenesis

Jacob Kang

 Introduction: Over 11 million people receive emergency treatment for burn wounds annually1. The surgical excision of subcutaneous tissue, necessary for skin grafting, often causes a deformity by creating an indentation. The injection of new adipose tissue, used as a cosmetic treatment, is hampered by insufficient angiogenesis for the survival of transplanted fat1,2. There has been considerable interest in inducing angiogenesis and adipogenesis to regenerate new subcutaneous tissue and fill soft tissue defects1. Studies have shown that trace amounts of silicon are involved in adipogenesis and angiogenesis in-vivo1. Other studies have demonstrated that low concentrations of bioactive silicon can induce the adipogenesis of human bone mesenchymal stem cells (HBMSCs) and the angiogenesis of human umbilical vein endothelial cells (HUVECs)3,4,5,6. These findings suggest that bioactive silicon ceramics could be used to regenerate subcutaneous adipose tissue in locations of burn wound surgical excision. This study attempts to identify the genetic mechanism by which silicon ions induce angiogenesis and adipogenesis. Methods: Human umbilical vein endothelial cells (HUVECs) and human bone mesenchymal stem cells (HBMSCs) were utilized. HUVECs and HBMSCs were cultured with increased concentrations of silicon ions. HBMSC adoption of the adipocyte phenotype was observed using Oil-Red-O staining of lipid droplets in high and low concentrations of silicon. Reverse transcription quantitative PCR (RT-qPCR) was used to measure the production of mRNAs associated with angiogenesis (VEGF, VEGF Receptor 2, IGF1, IGF1 Receptor). RT-qPCR also measured the production of mRNAs associated with adipogenesis (PPARy, C/EBPa, FABP4, leptin, adiponectin). Results: Bioactive silicon ions induced phenotypes and patterns of gene expression that are associated with adipogenesis and angiogenesis1. In HBMSCs, silicon ions significantly increased the rate of lipid droplet accumulation1. Bioactive silicon also induced the production of several adipogenic marker mRNAs (PPARy, C/EBPa, FABP4, leptin, and adiponectin). Both in HUVECs and co-cultured adipocytes, silicon induced the increased expression of mRNAs for IGF1, IGF1R, and VEGF. However, silicon only induced the production of VEGF receptor 2 mRNAs in HUVECs but not in adipocytes1. Conclusions: This study demonstrates that silicon ceramics can induce adipogenesis and angiogenesis by releasing bioactive silicon ions. Bioactive silicon ions induce adipogenesis by upregulating the expression of multiple genes associated with adipocyte differentiation. Bioactive silicon induces angiogenesis by upregulating the expression of the VEGF and IGF1 growth factors and their receptors. These factors may enable silicon to fill soft tissue defects.

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