Effects of MgO nanoparticle addition on the mechanical properties, degradation properties, antibacterial properties and in vitro and in vivo biological properties of 3D-printed Zn scaffolds.

Bone tissue engineering is the main method for repairing large segment bone defects. In this study, a layer of bioactive MgO nanoparticles was wrapped on the surface of spherical Zn powders, which allowed the MgO nanoparticles to be incorporated into 3D-printed Zn matrix and improved the biodegradation and biocompatibility of the Zn matrix. The results showed that porous pure Zn scaffolds and Zn/MgO scaffolds with skeletal-gyroid (G) model structure were successfully prepared by selective laser melting (SLM). The average porosity of two porous scaffolds was 59.3 and 60.0%, respectively. The pores were uniformly distributed with an average pore size of 558.6-569.3 µm. MgO nanoparticles regulated the corrosion rate of scaffolds, resulting in a more uniform corrosion degradation behavior of the Zn/MgO scaffolds in simulated body fluid solution. The degradation ratio of Zn/MgO composite scaffolds in vivo was increased compared to pure Zn scaffolds, reaching 15.6% at 12 weeks. The yield strength (10.8 ± 2.4 MPa) of the Zn/MgO composite scaffold was comparable to that of cancellous bone, and the antimicrobial rate were higher than 99%. The Zn/MgO composite scaffolds could better guide bone tissue regeneration in rat cranial bone repair experiments (completely filling the scaffolds at 12 weeks). Therefore, porous Zn/MgO scaffolds with G-model structure prepared with SLM are a promising biodegradable bone tissue engineering scaffold.

Antibacterial-Antioxidative Thiolated Gelatin/Methacrylated Silk Fibroin Hydrogels with Nitric Oxide Release Catalyzed by Metal-Polyphenol Nanoparticles for MRSA-Infected Wound Healing.

Chronic wound infection often leads to irregular tissue closure and accompanies delayed healing and economy issues. Developing an ideal wound dressing that can control the occurrence of antibacterial infections and biological responses is highly desirable. In this study, a multifunctional hybrid hydrogel (GS@EG-Cu-CA NPs) containing synthesized thiolated gelatin, methacrylated silk fibroin, and (-)-epigallocatechin gallate-copper ionic-carrageenan nanoparticles (EG-Cu-CA NPs) was engineered by a thio-ene click reaction. The metal-polyphenol EG-Cu-CA NPs were encapsulated with kappa-carrageenan to enhance its aqueous-soluble, mechanical, and bioactive properties and endowed the hydrogel dressing with fascinating antibacterial, antioxidation, and nitric oxide (NO) generation by catalyzing. The hybrid hydrogels also illustrated a favorable cytocompatibility. Benefiting from the thio-ene click reaction, the hybrid hydrogels were injected and photocured rapidly in situ to cover an irregular wound. In an SD rat full-thickness skin-wound-infected model, the methicillin-resistant Staphylococcus aureus-infected wound covered with GS@EG-Cu-CA NPs was almost completely healed after 10 days. This study presents a facile design of hydrogel dressing incorporating metal-polyphenol nanoparticles, which demonstrates a promising potential way for dealing with effective wound infection management and other complicated wound healings.

Silencing GMPPB Inhibits the Proliferation and Invasion of GBM via Hippo/MMP3 Pathways.

Glioblastoma multiforme (GBM) is a highly aggressive malignancy and represents the most common brain tumor in adults. To better understand its biology for new and effective therapies, we examined the role of GDP-mannose pyrophosphorylase B (GMPPB), a key unit of the GDP-mannose pyrophosphorylase (GDP-MP) that catalyzes the formation of GDP-mannose. Impaired GMPPB function will reduce the amount of GDP-mannose available for O-mannosylation. Abnormal O-mannosylation of alpha dystroglycan (α-DG) has been reported to be involved in cancer metastasis and arenavirus entry. Here, we found that GMPPB is highly expressed in a panel of GBM cell lines and clinical samples and that expression of GMPPB is positively correlated with the WHO grade of gliomas. Additionally, expression of GMPPB was negatively correlated with the prognosis of GBM patients. We demonstrate that silencing GMPPB inhibits the proliferation, migration, and invasion of GBM cells both in vitro and in vivo and that overexpression of GMPPB exhibits the opposite effects. Consequently, targeting GMPPB in GBM cells results in impaired GBM tumor growth and invasion. Finally, we identify that the Hippo/MMP3 axis is essential for GMPPB-promoted GBM aggressiveness. These findings indicate that GMPPB represents a potential novel target for GBM treatment.