Alendronate crosslinked chitosan/polycaprolactone scaffold for bone defects repairing
Alendronate crosslinked chitosan/polycaprolactone scaffold for bone defects repairing
- International Journal of Biological Macromolecules, 204, p.441-456, 2022 .
Here, we evaluated osteogenic differentiation in vitro and new bone formation in vivo using an alendronate-loaded chitosan/polycaprolactone scaffold (CS/PCL)in rats with a critical-sized calvarial defect. Through the action of genipin, which has a crosslinking function, alendronate (AL)was anchored throughout the CS/PCL composite scaffold (CS/PCL@AL)to form an AL sustained release system. We demonstrated that CS/PCL@AL scaffolds significantly enhanced the osteogenic differentiation of ectomesenchymal stem cells (EMSCs)in vitro. Additionally, we explored the possible molecular mechanism of CS/PCL@AL scaffolds in the osteogenic differentiation of EMSCs. This composite scaffold exerted two positive effects on EMSC osteogenic differentiation: 1)the CS/PCL@AL scaffold enhanced EMSC osteogenic differentiation by upregulating bone morphogenetic protein 2, interleukin 10 and laminin expression; and 2)the CS/PCL@AL scaffold promoted the osteogenic differentiation of EMSCs by activating the yes-associated protein (YAP)signaling pathway. YAP and its downstream target transglutaminase are crucial mediators in the osteogenic differentiation of EMSCs. Finally, micro-computed tomography analyses and histology results suggested that the CS/PCL@AL scaffold exhibited a superior capacity to accelerate new and mature bone formation in skull bone defects in Sprague-Dawley rats. This simple and low-cost technology may represent a promising strategy to construct an efficient delivery system to repair bone defects.
CHITOSAN
ALENDRONATE
PCL
Here, we evaluated osteogenic differentiation in vitro and new bone formation in vivo using an alendronate-loaded chitosan/polycaprolactone scaffold (CS/PCL)in rats with a critical-sized calvarial defect. Through the action of genipin, which has a crosslinking function, alendronate (AL)was anchored throughout the CS/PCL composite scaffold (CS/PCL@AL)to form an AL sustained release system. We demonstrated that CS/PCL@AL scaffolds significantly enhanced the osteogenic differentiation of ectomesenchymal stem cells (EMSCs)in vitro. Additionally, we explored the possible molecular mechanism of CS/PCL@AL scaffolds in the osteogenic differentiation of EMSCs. This composite scaffold exerted two positive effects on EMSC osteogenic differentiation: 1)the CS/PCL@AL scaffold enhanced EMSC osteogenic differentiation by upregulating bone morphogenetic protein 2, interleukin 10 and laminin expression; and 2)the CS/PCL@AL scaffold promoted the osteogenic differentiation of EMSCs by activating the yes-associated protein (YAP)signaling pathway. YAP and its downstream target transglutaminase are crucial mediators in the osteogenic differentiation of EMSCs. Finally, micro-computed tomography analyses and histology results suggested that the CS/PCL@AL scaffold exhibited a superior capacity to accelerate new and mature bone formation in skull bone defects in Sprague-Dawley rats. This simple and low-cost technology may represent a promising strategy to construct an efficient delivery system to repair bone defects.
CHITOSAN
ALENDRONATE
PCL