-
Munk Astrup posted an update 3 months, 1 week ago
RB@MPMW continuously phosphorylated AMPK and further rescued mitochondrial energy metabolism of chondrocytes following IL-1β stimulation via activating SIRT1-PGC-1α signaling pathway. Additionally, the cartilage-targeting property of peptide-modified nanocarrier could be monitored via Magnetic Resonance (MR) and IVIS imaging. More significantly, RB@MPMW effectively delayed cartilage degeneration in ACLT rat model. Overall, our findings indicated that the as-prepared dual-drug delivery nanoplatform exerted potent anti-inflammation and anti-apoptotic effects, rescued energy metabolism of chondrocytes in vitro and prevented cartilage degeneration in vivo, which thereby showed positive performance for OA therapy.Being the most abundant non-macromolecular organic component of bone, the role of citrate (Cit) in hydroxyapatite (HA) crystallization is of high relevance. In this work we have investigated the influence of hydroxycitrate (CitOH) and glutarate (Glr) on HA crystallization in terms of particle growth, composition, and morphology in comparison to Cit. FTY720 CitOH and Glr have been selected for this work because they share the same backbone structure of Cit but bear different functional groups in the central region. Our data has revealed that CitOH strongly inhibits HA crystallization more efficiently than Cit. CitOH-HA nanoparticles are composed of platy, elongated particles similar to those of Cit-HA but they are ca. twice smaller and have a lower crystal order. On the other hand, Glr does not inhibit HA crystallization as Cit, but leads to the formation of OCP platelets that convert with maturation time to HA nanorods with larger aspect ratio than Cit-HA. In comparison to Cit-HA samples, Glr-HA nanoparticles have bigger dimensions, and higher structural order. Overall, our data reveal that the central carboxyl group of Cit is involved in the selective binding with HA crystal surface and in regulating HA crystal growth. The results of this work highlight new possibilities to control the formation of HA for designing advanced bioactive materials and give new insights on the role of the structure of Cit in regulating the HA morphology.The development of an excellent, bioabsorbable hemostatic material for deep wound remains a challenge. In this work, a biodegradable cotton-like biomimetic fibrous mat of poly (l-lactic acid) (PLLA) was made by melt spinning. Subsequently, SD composite was prepared by cross-linking sodium alginate (SA) with dopamine (DA). It was immobilized on the fibre surface, which inspired by mussel byssus. Finally, Fe3+ was loaded onto the 0.5SD/PLLA composite by chelation with the carboxyl of alginate and phenolic hydroxy of dopamine. The haemostasis experiment found that the hemostatic time 47 s in vitro. However, the bleeding volume was 0.097 g and hemostatic time was 23 s when 20Fe3+-0.5SD/PLLA was applied in the haemostasis of the rat liver. As a result of its robust hydrophilicity and bouffant cotton-like structure, it could absorb a large water from blood, which could concentrate the component of blood and reduce the clotting time. Furthermore, the addition of Fe3+ in the 0.5SD/PLLA had a significant effect on improve hemostatic property. It also displayed excellent antibacterial property for Escherichia coli and Staphylococcus aureus. Notably, it possesses superior hemocompatibility, cytocompatibility and histocompatibility. Hence, 20Fe3+-0.5SD/PLLA has high potential application in haemostasis for clinical settings due to its outstanding properties.Artificial prostheses for joint replacement are indispensable in orthopedic surgery. Unfortunately, the implanted surface is attractive to not only host cells but also bacteria. To enable better osteointegration, a mechanically stable porous structure was created on a titanium surface using laser treatment and metallic silver particles were embedded in a hydrophilic titanium oxide layer on top. The laser structuring resulted in unique amphora-shaped pores. Due to their hydrophilic surface conditions and capillary forces, the pores can be loaded preoperative with the antibiotic of choice/need, such as gentamicin. Cytotoxicity and differentiation assays with primary human osteoblast-like cells revealed no negative effect of the surface modification with or without gentamicin loading. An in vivo biocompatibility study showed significantly enhanced osteointegration as measured by push-out testing and histomorphometry 56 days after the implantation of the K-wires into rat femora. Using a S. aureus infection model, the porous, silver-coated K-wires slightly reduced the signs of bone destruction, while the wires were still colonized after 28 days. Loading the amphora-shaped pores with gentamicin significantly reduced the histopathological signs of bone destruction and no bacteria were detected on the wires. Taken together, this novel surface modification can be applied to new or established orthopedic implants. It enables preoperative loading with the antibiotic of choice/need without further equipment or post-coating, and supports osteointegration without a negative effect of the released dug, such as gentamicin.The design of orthopedic biomaterials has gradually shifted from “immune-friendly” to “immunomodulatory,” in which the biomaterials are able to modulate the inflammatory response via macrophage polarization in a local immune microenvironment that favors osteogenesis and implant-to-bone osseointegration. Despite the well-known effects of bioactive metallic ions on osteogenesis, how extracellular metallic ions manipulate immune cells in bone tissue microenvironments toward osteogenesis and subsequent bone formation has rarely been studied. Herein, we investigate the osteoimmunomodulatory effect of an extracellular bioactive cation (Mg2+) in the bone tissue microenvironment using custom-made poly lactic-co-glycolic acid (PLGA)/MgO-alendronate microspheres that endow controllable release of magnesium ions. The results suggest that the Mg2+-controlled tissue microenvironment can effectively induce macrophage polarization from the M0 to M2 phenotype via the enhancement of anti-inflammatory (IL-10) and pro-osteogenic (BMP-2 and TGF-β1) cytokines production.