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

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)-1ß, 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.

Ginsenoside Rb1/TGF-ß1 loaded biodegradable silk fibroin-gelatin porous scaffolds for inflammation inhibition and cartilage regeneration.

Creating a microenvironment with low inflammation and favorable for the chondrogenic differentiation of endogenous stem cells plays an essential role in cartilage repairing. In the present study, we design a novel ginsenoside Rb1/TGF-ß1 loaded silk fibroin-gelatin porous scaffold (GSTR) with the function of attenuating inflammation and promoting chondrogenesis. The scaffold has porous microstructure, proper mechanical strength, degradation rate and sustained release of Rb1 and TGF-ß1. Rat bone marrow-derived mesenchymal stem cells (rBMSCs) seeded into GSTR scaffolds are homogeneously distributed and display a higher proliferation rate than non-loaded scaffolds (GS). GSTR scaffolds promote the chondrogenic differentiation of rBMSCs and suppress the expression of inflammation genes. Under the stimulation of IL-1ß, the inflammation level of the chondrocytes seeded in GSTR scaffolds is also significantly down-regulated. Moreover, GSTR scaffolds implanted into the osteochondral defects in rats effectively promote the regeneration of hyaline cartilage 12 weeks after surgery when compared with other groups. It is demonstrated that this scaffold loaded with Rb1 and TGF-ß1 can synergistically create a microenvironment favorable for cartilage regeneration by promoting the chondrogenesis and suppressing the inflammation levels in vivo. These results prove it has a great potential to develop this Rb1/TGF-ß1 releasing scaffold into a novel and promising therapeutic for cartilage repair.

Sustained Release SDF-1α/TGF-ß1-Loaded Silk Fibroin-Porous Gelatin Scaffold Promotes Cartilage Repair.

Continuous delivery of growth factors to the injury site is crucial to creating a favorable microenvironment for cartilage injury repair. In the present study, we fabricated a novel sustained-release scaffold, stromal-derived factor-1α (SDF-1α)/transforming growth factor-ß1 (TGF-ß1)-loaded silk fibroin-porous gelatin scaffold (GSTS). GSTS persistently releases SDF-1α and TGF-ß1, which enhance cartilage repair by facilitating cell homing and chondrogenic differentiation. Scanning electron microscopy showed that GSTS is a porous microstructure and the protein release assay demonstrated the sustainable release of SDF-1α and TGF-ß1 from GSTS. Bone marrow-derived mesenchymal stem cells (MSCs) maintain high in vitro cell activity and excellent cell distribution and phenotype after seeding into GSTS. Furthermore, MSCs acquired enhanced chondrogenic differentiation capability in the TGF-ß1-loaded scaffolds (GSTS or GST: loading TGF-ß1 only) and the conditioned medium from SDF-1α-loaded scaffolds (GSTS or GSS: loading SDF-1α only) effectively promoted MSCs migration. GSTS was transplanted into the osteochondral defects in the knee joint of rats, and it could promote cartilage regeneration and repair the cartilage defects at 12 weeks after transplantation. Our study shows that GSTS can facilitate in vitro MSCs homing, migration, chondrogenic differentiation and SDF-1α and TGF-ß1 have a synergistic effect on the promotion of in vivo cartilage forming. This SDF-1α and TGF-ß1 releasing GSTS have promising therapeutic potential in cartilage repair.

Study on the stability control strategy of Triphala solution based on the balance of physical stability and chemical stabilities.

Triphala is a well-known prescription in Indian Ayurveda and TCM medicine for its great effect on gingivitis and hyperlipidemia. However, its solution is unstable for the containing of excessive polyphenol, leading to the production of sediment in the short term and the decrease of efficacy. Based on the analysis of sediment formation, a novel control strategy is proposed. To conduct the analysis, the sediment formation was recorded for a consecutive five days. The changes in the composition of the supernatant and the sediment were studied by the HPLC profile analysis. The main components of the sediment were identified as corilagin, ellagic acid and gallic acid, and the amount of ellagic acid sediment increased with the storage time. Then, with a series of pH status adjustments of the Triphala solution, the physical and chemical stabilities were acquired by Turbiscan and HPLC respectively. The results showed that as the pH value increased, so did the physical stability, but the particle size and TSI of the association decreased. While the fingerprint of chemical profile similarity decreased, so did the chemical stability. Combining physical and chemical stability parameters, an equilibrium point was found out. When the pH value was adjusted to 5.0, both the physical and chemical stabilities were better: the verification test showed that the sedimentation inhibition rates on the 3rd, 5th,10th and15th days were 41%, 55%, 41%, and 23%, respectively. This manuscript provided a new control strategy that will pique pharmaceutical and food development engineers' interest and trigger research ideas controlling the quality of decoction.