Enhanced osteogenesis and angiogenesis by mesoporous hydroxyapatite microspheres-derived simvastatin sustained release system for superior bone regeneration

Abstract

Biomaterials with both excellent osteogenic and angiogenic activities are desirable to repair massive bone defects. In this study, simvastatin with both osteogenic and angiogenic activities was incorporated into the mesoporous hydroxyapatite microspheres (MHMs) synthesized through a microwave-assisted hydrothermal method using fructose 1,6-bisphosphate trisodium salt (FBP) as an organic phosphorous source. The effects of the simvastatin-loaded MHMs (S-MHMs) on the osteogenic differentiation of rat bone marrow mesenchymal stem cells (rBMSCs) and angiogenesis in EA.hy926 cells were investigated. The results showed that the S-MHMs not only enhanced the expression of osteogenic markers in rBMSCs but also promoted the migration and tube formation of EA.hy926 cells. Furthermore, the S-MHMs were incorporated into collagen matrix to construct a novel S-MHMs/collagen composite scaffold. With the aid of MHMs, the water-insoluble simvastatin was homogenously incorporated into the hydrophilic collagen matrix and presented a sustained release profile. In vivo experiments showed that the S-MHMs/collagen scaffolds enhanced the bone regeneration and neovascularization simultaneously. These results demonstrated that the water-insoluble simvastatin could be incorporated into the MHMs and maintained its biological activities, more importantly, the S-MHMs/collagen scaffolds fabricated in this study are of immense potential in bone defect repair by enhancing osteogenesis and angiogenesis simultaneously.

3D‐Bioprinted Osteoblast‐Laden Nanocomposite Hydrogel Constructs with Induced Microenvironments Promote Cell Viability, Differentiation, and Osteogenesis both In Vitro and In Vivo

“…While osteoblasts and fibroblasts can be observed within the ROB‐laden PEG4K–Clay scaffolds, new bone can also be clearly observed around and within the scaffolds. H&E staining22, 23 was used to further validate the Giemsa staining results (Figure 5). The results were consistent with the data collected from micro‐CT and new bone labeling analyses, verifying that PEG4K–Clay nanocomposite hydrogel scaffolds can stimulate new bone formation, and that the loading of exogenous cells into the scaffolds through 3D‐bioprinting has further positive implications for bone regeneration.…”

“…Hematoxylin (Sigma‐Aldrich, St. Louis, USA) and eosin (C0105, Beyotime Biotechnology, Shanghai, China) (H&E) staining22 and Goldner's staining24 were used to detect the specific tissue response to the implanted materials. Images were taken under the fluorescence microscope (Olympus, BX53, Tokyo, Japan).…”

Ca2+ Flux: Searching for a Role in Efferocytosis of Apoptotic Cells in Atherosclerosis

“…In addition to DRP1, MCU is also involved in this process, and its downregulation results in mitochondria-mediated defective efferocytosis in the Ldlr −/− /Drp1 −/− mice. These findings were proven by dexamethasone as an inducer of thymocyte apoptosis and resulted in defective efferocytosis [125]. Park et al have shown that the mitochondrial membrane uncoupling protein 2 (UCP2) was upregulated in phagocytes engulfing ACs [126].…”

“…Accordingly, the factors that influence the continued clearance of ACs by phagocytes are vital for efficient efferocytosis [121]. Degradation of the ingested AC and vesicular trafficking in the phagocyte are essential for engulfing another AC [125]. Mitochondrial fission facilitates appropriately digestion of AC-derived debris and vesicular trafficking, both of which are Ca 2+ -dependent in mice [125].…”

“…Degradation of the ingested AC and vesicular trafficking in the phagocyte are essential for engulfing another AC [125]. Mitochondrial fission facilitates appropriately digestion of AC-derived debris and vesicular trafficking, both of which are Ca 2+ -dependent in mice [125]. Therefore, through mitochondrial fission, macrophages can clear additional ACs in response to AC uptake, a capacity which is necessary for an apoptotic microenvironment in vivo [125].…”