Oxygen vacancy-enhanced catalytic activity of hyaluronic acid covered-biomineralization nanozyme for reactive oxygen species-augmented antitumor therapy.

Insufficient hydrogen peroxide content in tumor cells, unsuitable pH and low efficiency of commonly used metal catalysts severely affect the efficiency of chemodynamic therapy, resulting in unsatisfactory efficacy of chemodynamic therapy alone. For this purpose, we designed a composite nanoplatform capable of targeting tumors and selectively degrading in the tumor microenvironment (TME) to address these issues. In this work, we synthesized Au@Co3O4 nanozyme inspired by crystal defect engineering. The addition of Au determines the formation of oxygen vacancies, accelerates electron transfer, and enhances redox activity, thus significantly enhancing the superoxide dismutase (SOD)-like and catalase (CAT)-like catalytic activities of the nanozyme. Subsequently, we camouflaged the nanozyme using a biomineralized CaCO3 shell to avoid damage to normal tissues by the nanozyme while effectively encapsulating the photosensitizer IR820, and finally the tumor targeting ability of the nanoplatform was enhanced by the modification of hyaluronic acid. Under near-infrared (NIR) light irradiation, the Au@Co3O4@CaCO3/IR820@HA nanoplatform not only visualizes the treatment with multimodal imaging, but also plays a photothermal sensitizing role through various strategies, while enhancing the enzyme catalytic activity, cobalt ion-mediated chemodynamic therapy (CDT) and IR820-mediated photodynamic therapy (PDT), and achieving the synergistic enhancement of reactive oxygen species (ROS) generation.

Octahedral Pt-MOF with Au deposition for plasmonic effect and Schottky junction enhanced hydrogenothermal therapy of rheumatoid arthritis.

Hydrogen (H2) therapy is a novel and rapidly developing strategy utilized to treat inflammatory diseases. However, the therapeutic efficacy of H2 is largely limited with on-target off-synovium toxic effect, nonpolarity and low solubility. Herein, an intelligent H2 nanogenerator based upon the metal-organic framework (MOF) loaded with polydopamine and Perovskite quantum dots is constructed for the actualization of hydrogenothermal therapy. The biodegradable polydopamine with excellent photothermal conversion efficiencies is used for photothermal therapy (PTT) of rheumatoid arthritis (RA) and perovskite quantum dots (QDs) with unique photophysical properties are used as fluorescent signals for positioning Pt-MOF@Au@QDs/PDA nanoparticles. In addition, the Pt-MOF@Au@QDs/PDA catalyzer combines Au's surface plasmon resonance excitation with Pt-MOF Schottky junction, and exhibits extremely efficient photocatalytic H2 production under visible light irradiation. The Pt-MOF@Au@QDs/PDA achieves the aggregation of rheumatoid synovial cells by the extravasation through "ELVIS" effect (extravasation through leaky vasculature and subsequent inflammatory cell-mediated sequestration) and extremely efficient photocatalytic H2 production. By combining PTT and H2 therapy, the Pt-MOF@Au@QDs/PDA relieves the oxidative stress of RA, and shows significant improvement in joint damage and inhibition of the overall arthritis severity of collagen-induced RA mouse models. Therefore, the Pt-MOF@Au@QDs/PDA shows great potential in the treatment of RA and further clinical transformation.

Treatment with soluble bone morphogenetic protein type 1A receptor fusion protein alleviates irradiation-induced bone loss in mice through increased bone formation and reduced bone resorption.

An increased fracture risk is often observed in cancer patients undergoing radiotherapy (RT), particularly at sites within the field of radiation. Therefore, the development of appropriate therapeutic options to prevent RT-induced bone loss is urgently needed. A soluble form of the BMP receptor type 1A fusion protein (mBMPR1A-mFc) serves as an antagonist to endogenous BMPR1A. Previous studies have shown that mBMPR1A-mFc treatment increases bone mass in both ovary-intact and ovariectomized via promoting osteoblastic bone formation and inhibiting osteoclastic bone resorption. The present study was designed to investigate whether mBMPR1A-mFc administration prevents radiation-induced bone deterioration in mice. We constructed an animal model of radiation-induced osteoporosis by exposure to a 2-Gy dose of X-rays. Micro-CT, histomorphometric, bone-turnover, and mechanical analyses showed that mBMPR1A-mFc administration prevented trabecular microarchitecture deterioration after RT because of a marked increase in bone formation and a decrease in bone resorption. Mechanistic studies indicated that mBMPR1A-mFc administration promoted osteoblastogenesis by activating Wnt/Lrp5/ß-catenin signaling while decreasing osteoclastogenesis by inhibiting the RANKL/RANK/OPG pathway. Our novel findings provide solid evidence for the application of mBMPR1A-mFc as a therapeutic treatment for radiation-induced osteoporosis.

PRP-chitosan thermoresponsive hydrogel combined with black phosphorus nanosheets as injectable biomaterial for biotherapy and phototherapy treatment of rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease causing destruction of bone and cartilago articularis. Traditional treatment methods have many side effects, or too concerne about the anti-inflammatory mechanisms but ignore osteanagenesis. In this work, a novel therapeutic platform combined black phosphorus nanosheets (BPNs) into platelet-rich plasma (PRP)-chitosan thermoresponsive hydrogel has been prepared for management of RA. The BPNs generate local heat upon near-infrared irradiation, and delivering reactive oxygen species (ROS) to the inflamed joints simultaneously for removing hyperplastic synovial tissue. The injectable chitosan thermoresponsive hydrogel can take control of the releasing of BPNs degradation products, which provide ample raw materials for osteanagenesis. In addition, the PRP can effectively improve the adhesion and increase capacity of mesenchymal stem cells on chitosan thermosensitive hydrogels. And this thermoresponsive hydrogel can protect articular cartilage by reducing the friction on the surrounding tissue. Drug delayed release property was indicated by the release and uptake of methotrexate. The edema degree of the arthritic mouse was reduced obviously by the BPNs/Chitosan/PRP thermoresponsive hydrogel. Both in vitro and in vivo studies suggest that the thermoresponsive hydrogel can provide a potential possibility for the management of RA.

Three-Dimensional High-Porosity Chitosan/Honeycomb Porous Carbon/Hydroxyapatite Scaffold with Enhanced Osteoinductivity for Bone Regeneration.

Three-dimensional honeycomb porous carbon (HPC) has attracted increasing attention in bioengineering due to excellent mechanical properties and a high surface-to-volume ratio. In this paper, a three-dimensional chitosan (CS)/honeycomb porous carbon/hydroxyapatite composite was prepared by nano-sized hydroxyapatite (nHA) on the HPC surface in situ deposition, dissolved in chitosan solution, and vacuum freeze-dried. The structure and composition of CS/HPC/nHA were characterized by scanning electron microscopy, transmission electron miscroscopy, Fourier transform infrared, and X-ray photoelectron spectroscopy, and the porosity, swelling ratio, and mechanical properties of the scaffold were also tested. The as-prepared scaffolds possess hierarchical pores and organic-inorganic components, which are similar in composition and structure to bone tissues. The synthesized composite scaffold has high porosity and a certain mechanical strength. By culturing mouse bone marrow mesenchymal stem cells on the surface of the scaffold, it was confirmed that the scaffold facilitated its growth and promoted its differentiation into the osteogenesis direction. In vivo experiments further demonstrate that the CS/HPC/nHA composite scaffold has a significant advantage in promoting bone formation in the bone defect area. All the results suggested that the CS/HPC/nHA scaffolds have great application prospect in bone tissue engineering.

Bioactive Three-Dimensional Graphene Oxide Foam/Polydimethylsiloxane/Zinc Silicate Scaffolds with Enhanced Osteoinductivity for Bone Regeneration.

Nanocomposite scaffold materials have shown great prospect in promoting bone integration and bone regeneration. A three-dimensional graphene oxide foam/polydimethylsiloxane/zinc silicate (GF/PDMS/ZS) scaffold for bone tissue engineering was synthesized via dip coating and hydrothermal synthesis processes, resulting in the interconnected macroporous structure. The scaffold was characterized with scanning electron microscopy (SEM), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), and thermogravimetric (TG) analysis. The result showed that scaffolds exhibiting a porous characteristic had organic-inorganic components similar to natural bone tissue. Moreover, the scaffolds possessed suitable pore size, high porosity, and good mechanical properties. In vitro experiments with mouse bone marrow mesenchymal stem cells (mBMSCs) revealed that the composite scaffold not only has great biocompatibility but also has the ability to induce mBMSC proliferation and preferential osteogentic differentiation. Thereafter, the expression of critical genes, ALP, RUNX2, VEGFA, and OPN, was activated. In vivo analysis of critical bone defect in rabbits demonstrated superior bone formation in defect sites in the GF/PDMS/ZS scaffold group at 12 weeks of post implantation without no significant inflammatory response. All the results validated that the GF/PDMS/ZS scaffold is a promising alternative for applications in bone regeneration.

Three-Dimensionally N-Doped Graphene-Hydroxyapatite/Agarose as an Osteoinductive Scaffold for Enhancing Bone Regeneration.

Composite biomaterials with hierarchical structures have emerged as new approaches for bone-tissue engineering. In this study, a biomimetic, osteoconductive tricomposite scaffold made of N-doped graphene-hydroxyapatite (NG-HA) hybrids blended with an agarose (AG) matrix was prepared via a facile hydrothermal/cross-linking/freeze-drying method. The structure and composition of AG/NG-HA were examined by scanning electron microscopy, X-ray photoelectron spectroscopy, X-ray diffraction, Fourier transform infrared, Raman spectroscopy, and thermogravimetric analysis. The as-prepared scaffolds showed hierarchical pore architecture and an organic-inorganic composition, which simulated the composition and structure of natural bone tissue. The effect of AG/NG-HA on bone mesenchymal stem cells (MSCs) osteoblast proliferation, differentiation, and mineralization was tested in vitro. The expression of osteogenic-related genes was determined by real-time polymerase chain reaction. Our results showed that the introduction of N-graphene into the hybrid scaffold significantly improved its mechanical properties, an effect that promoted the proliferation and viability of MSCs. Moreover, the scaffolds triggered selective differentiation of MSCs to osteogenic lineage while conferring good cell adhesion, enhanced alkaline phosphatase activity, and mineralization. A distal femoral condyle critical size defect in rabbits was used as a platform to confirm the effect of AG/NG-HA on bone regeneration in vivo. Our experiments show that the AG/NG-HA hybrid scaffolds provided a favorable environment for new bone formation. The results presented in this study suggest that the AG/NG-HA hybrid scaffolds have potential in bone-tissue regeneration engineering.