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 fat^1,2. 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.

1. Varkey M, Visscher DO, van Zuijlen PPM, Atala A, Yoo JJ. Skin bioprinting: the future of burn wound reconstruction? Burns Trauma. 2019 Feb 12;7:4. 2.
2. Wang X, Gao L, Han Y, Xing M, Zhao C, Peng J, Chang J. Silicon-Enhanced Adipogenesis and Angiogenesis for Vascularized Adipose Tissue Engineering. Adv Sci (Weinh). 2018 Sep 30;5(11):1800776.
3. Li H, Xue K, Kong N, Liu K, Chang J. Silicate bioceramics enhanced vascularization and osteogenesis through stimulating interactions betweenendothelial cells and bone marrow stromal cells. Biomaterials. 2014Apr;35(12):3803-18.
4. Li H, Chang J. Bioactive silicate materials stimulate angiogenesis infibroblast and endothelial cell co-culture system through paracrine effect. Acta Biomater. 2013 Jun;9(6):6981-91.
5. Xia L, Yin Z, Mao L, et al. Akermanite bioceramics promote osteogenesis, angiogenesis and suppress osteoclastogenesis for osteoporotic bone regeneration. Sci Rep. 2016;6:22005. Published 2016 Feb 25.
6. Monte F, Cebe T, Ripperger D, Ighani F, Kojouharov HV, Chen BM, Kim HKW,Aswath PB, Varanasi VG. Ionic silicon improves endothelial cells’ survival under toxic oxidative stress by overexpressing angiogenic markers and antioxidant enzymes. J Tissue Eng Regen Med. 2018 Nov;12(11):2203-2220.