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Bioactive strontium ions/ginsenoside Rg1-incorporated biodegradable silk ﬁbroin-gelatin scaffold promoted challenging osteoporotic bone regeneration.

ABSTRACT: Autogenous healing of osteoporotic fractures is challenging, as the regenerative capacity of bone tissues is impaired by estrogen reduction and existed pro-inflammatory cytokines. In this study, a biofunctional ginsenoside Rg1 and strontium-containing mineral (SrHPO₄, SrP)-incorporated biodegradable silk ﬁbroin-gelatin (SG) scaffold (Rg1/SrP/SG) was developed to stimulate the osteoporotic bone repair. The incorporation of 15 wt% SrP significantly enhanced the mechanical strength, stimulated the osteogenic differentiation of mouse bone marrow mesenchymal stem cells, and suppressed the osteoclastogenesis of RAW264.7 in a concentration-related manner. The loading of Rg1 in SG and 15SrP/SG scaffolds obviously promoted the angiogenesis of human umbilical vein endothelial cells via activating the expression of vascular endothelial growth factor and basic fibroblast growth factor genes and proteins. The bioactive strontium ions (Sr²⁺) and Rg1 released from the scaffolds together mediated lipopolysaccharide-treated macrophages polarizing into M2 type. They downregulated the expression of inflammatory-related genes (interleukin (IL)-1β, tumor necrosis factor α, and IL-6) and stimulated the expression of genes related to anti-inflammation (Arginase and IL-10) as well as bone repair (BMP-2 and PDGF-BB) in the macrophages. The in vivo results also displayed that SrP and Rg1 significantly promoted the bone repair effect of SG scaffolds in osteoporotic critical-sized calvarial defects. Besides, the degradation rate of the scaffolds was close to the bone regeneration rate. Therefore, the simultaneous addition of SrP and Rg1 is a promising way for facilitating the osteoporotic bone repair activity of SG scaffolds via promoting the osteogenesis and angiogenesis, as well as inhibiting the osteoclastogenesis and inflammation.

SUBMITTER: Wu T

PROVIDER: S-EPMC8488313 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:The present study investigated the effect and underlying mechanisms of ginsenoside Rg1 (Rg1) in attenuating subacute liver injury induced by D-galactose (D-gal) in mice. Specific Pathogen Free (SPF) male C57BL/6J mice were randomly divided into 3 groups: i) D-gal-administration group (D-gal group), where the mice were intraperitoneally administrated with D-gal (120 mg/kg/day for 42 days); ii) D-gal + Rg1 group where the mice were treated with 120 mg/kg/day D-gal for 42 days and with Rg1 at a dose of 20 mg/kg/day for 35 days. The first dose of Rg1 was administered on the 8th day of treatment with D-gal; and iii) the normal control group, where the mice were injected with an equal volume of saline for 42 days. The day following the final injections in all groups, peripheral blood was collected and serum was prepared to measure the contents of aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (TBiL), advanced glycation end products (AGEs) and 8-hydroxy-2 deoxyguanosine (8-OH-dG). Liver tissue homogenates were prepared to measure the contents of malondialdehyde (MDA) and glutathione (GSH), and the activities of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD). Paraffin section were prepared to observe the microscopic structure of the liver. Transmission electron microscopy was used to observe the ultrastructure of hepatocytes. Frozen section were prepared and stained with senescence-associated ?-galactosidase to detect the relative optical density value of senescence-associated markers. Compared with the D-gal group, the contents of AST, ALT, TBiL, AGEs and MDA significantly decreased in the D-gal + Rg1 group, while the activities of SOD and GSH-Px markedly increased, and liver injury and degenerative alterations of hepatocytes were reduced. Administration of Rg1 induced a protective effect on D-gal-induced liver injury in mice by inhibiting the oxidative stress, reducing DNA damage and decreasing the AGE content.

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Bioactive strontium ions/ginsenoside Rg1-incorporated biodegradable silk ﬁbroin-gelatin scaffold promoted challenging osteoporotic bone regeneration.

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