The design and development of novel cell-mediated and gene-activated bioactive materials has become one of important research fields for tissue regeneration. In this study, the new type of bioactive materials: microano-bioactive glasses (MNBG) were prepared using organic template synthesis combined with sol-gel technology. These new bioactive glasses possess high surface area, good cell compatibility, rapid bone bonding and the ability to stimulate new bone formation, enhance angiogenesis and wound healing. This research explained the detailed mechanisms on the cell-mediated and gene-activated function for osteogenesis, vascularization and wound healing related cells and genes. Firstly, when BG was co-cultured with osteoblasts, both BG contacted cells and surrounding cells experienced proliferation and differentiation, and the mRNA level of the bone healing maker such as osteocalcin, alkaline phosphatase and osteopontin were significantly up-regulated, which confirmed the gene-activated function of ionic dissolution products from bioactive glass on surrounding cells, and the gene activation effects can be directly affected by the ionic release quantity. Our study also showed that the p38 and ERK signaling pathways was activated in MSCs (mesenchymal stem cells), resulting in the directional differentiation into the osteoblasts. The released Si and Ca further promoted the expressions of the osteogenic genes and proteins, such as the Runx 2, ALP and OCN. Therefore, we concluded that the osteogenesis of BG was not only related to the fast biomineralization process, but also depended on the cell-mediated and gene-activated functions. Moreover, MNBG could activate the VEGF (vascular endothelial growth factor) signaling pathway and up-regulate the expressions of angiogenic genes and proteins such as the VEGF and VEGF receptor, resulting in the faster proliferation, migration and angiogensis of the endothelial cells. Futhermore, in vivo study showed that the TGF-β (Transforming growth factor-β) signaling pathway was also activated with the high level expression of α-SMA and collagen Ⅰ genes and proteins. Those co-effects resulted in the faster and better healing process of the normal and diabetic cutaneous wounds. In conclusion, Micro-ano-bioactive glasses could be a promissing kind of biomaterials for hard tissue repair, and cutaneous wound healing.
展开▼
