Stiffness and BMP-2 Mimetic Peptide Jointly Regulate the Osteogenic Differentiation of Rat Bone Marrow Stromal Cells in a Gelatin Cryogel.

Both biochemical and mechanical cues could regulate the function of stem cells, but the interaction mechanism of their signaling pathway remains unclear, especially in the three-dimensional (3D) culture mode. Higher matrix stiffness promotes osteogenic differentiation of stem cells, and bone morphogenic protein-2 (BMP-2) has been clinically applied to promote bone regeneration. Here, the crosstalk of extracellular mechanical signals on BMP-2 signaling was investigated in rat bone marrow stromal cells (rMSCs) cultured inside cryogels with interconnective pores. Stiff cryogel independently promoted osteogenic differentiation and enhanced the autocrine secretion of BMP-2, thus stimulating increased phosphorylation levels of the Smad1/5/8 complex. BMP-2 mimetic peptide (BMMP) and high cryogel stiffness jointly guided the osteogenic differentiation of rMSCs. Inhibition of rho-associated kinase (ROCK) by Y-27632 or inhibition of nonmuscle myosin II (NM II) by blebbistatin showed that osteogenesis induction by BMP-2 signaling, as well as autocrine secretion of BMP-2 and phosphorylation of the Smad complex, requires the involvement of cytoskeletal tension and ROCK pathway signaling. An interconnective microporous cryogel scaffold promoted rMSC osteogenic differentiation by combining matrix stiffness and BMMP, and it accelerated critical cranial defect repair in the rat model.

Quercetin-loaded porous biocomposite of polyimide and molybdenum disulfide nanosheets with antibacterial capability for boosting osteoblastic differentiation and bone-bonding.

Implant instability and bacterial infection are the two main reasons for the failure of bone implantation. Herein, a porous biocomposite containing polyimide (PI) and 40 w% molybdenum disulfide (MoS2) nanosheets (PM40) was fabricated, and quercetin (QT) was loaded onto the porous surface of PM40 (PMQT). Incorporation of MoS2 nanosheets into PI remarkably increased the compressive strength, water absorption and protein absorption of PM40. PM40 exhibited good antibacterial capability owing to presence of MoS2, while PMQT displayed the further enhancement of antibacterial capability because of loading of QT. PM40 with MoS2 significantly stimulated the osteoblastic differentiation of bone mesenchymal stem cells in vitro, and PMQT with QT displayed further enhancement. In comparison with PI and PM40, PMQT significantly inhibited the osteoclastic differentiation thanks to the sustained-release of QT that suppressed the formation of osteoclasts and expression of osteoclastic genes. Moreover, PM40 with MoS2 accelerated osteogenesis and bone-bonding in vivo, and PMQT with QT displayed further enhancement. In summary, the cooperative effect of MoS2 and QT significantly improved osteoblastic differentiation and ameliorated bone-bonding in vivo. Accordingly, PMQT displayed marvelous osteogenic and antibacterial effects, which would have the potential for repair of load-bearing bone.

A bioactive poly(ether-ether-ketone) nanocomposite scaffold regulates osteoblast/osteoclast activity for the regeneration of osteoporotic bone.

Due to the lower regeneration capacity of the osteoporotic bone, the treatment of osteoporotic defects is extremely challenging in clinics. In this study, strontium-doped bioactive glass nanoparticles loaded with sodium alendronate (ALN), namely A-SrBG, were incorporated into the poly(ether-ether-ketone) matrix to fabricate a bioactive composite scaffold (ASP), which was expected to both inhibit bone resorption and promote bone regeneration. The results showed that such a composite scaffold with interconnected macropores (200-400 µm) could release Ca2+, Sr2+, and ALN in vitro. The proliferation, alkaline phosphatase (ALP) activity, expression of osteogenesis-related genes, and formation of calcified nodules of rat bone marrow stromal cells (rBMSCs) were clearly evidenced, and the reduction in the proliferation, tartrate-resistant acid phosphatase (TRAP) activity, cell fusion, and expression of osteoclastogenesis-related genes of osteoclasts was observed as well. In the presence of the ASP scaffold, enhanced osteogenesis along with inhibiting osteoclastogenesis was observed by modulating the osteoprotegerin (OPG)/receptor activator for nuclear factor κB ligand (RANKL) ratio. The efficacy of the composite scaffold in the regeneration of osteoporotic critical-sized cranial defect in a rat model was evaluated. Therefore, the bioactive composite scaffold with excellent biocompatibility and osteogenic potential could be a promising material for the repair of osteoporotic bone defects.

Macrophage-targeting bioactive glass nanoparticles for the treatment of intracellular infection and subcutaneous abscess.

Staphylococcus aureus (S. aureus) can survive phagocytosis and gain shelter from macrophages in some cases, and the clinical treatment of the intracellular bacterium also encounters the difficulty of traditional antibiotics in entering mammalian cells. In this work, we use mannose-modified bioactive glass nanoparticles decorated with silver nanoparticles (BGNs-Man/Ag) to treat the S. aureus-induced intracellular infection of macrophages. The results showed that BGNs-Man/Ag could target macrophages, elevate the intracellular ROS levels and drive them toward the M1 phenotype, which was crucial to activate the cell autonomous defence in disposing the intracellular infection. Attractively, BGNs-Man/Ag exhibited higher intracellular bacterial killing efficiency than free vancomycin. For the in vivo treatment of subcutaneous abscess, BGNs-Man/Ag significantly increased the population of M1 macrophages at the early stages of the infection site, resulting in enhanced bactericidal activity and improved regeneration of skin tissues. In short, BGNs-Man/Ag can be a promising antibacterial material in treating the S. aureus-induced intracellular infection of macrophages and subcutaneous abscesses.

Copper-Doped Bioactive Glass/Poly (Ether-Ether-Ketone) Composite as an Orbital Enucleation Implant in a Rabbit Model: An In Vivo Study.

An orbital enucleation implant is used to compensate for the orbital volume deficits in the absence of the globe. In this work, copper-doped bioactive glass in poly(ether-ether-ketone) (CuBG/PEEK) composite scaffolds as an orbital enucleation implant were designed and fabricated by cool-pressed sintering and particle-leaching techniques, the incorporation of copper-doped bioactive glass in poly(ether-ether-ketone) (CuBG/PEEK) was expected to significantly improve the biocompatibility of the PEEK implant. The consequences after implantation of the CuBG/PEEK composite scaffolds in experimental, eviscerated rabbits was observed and assayed in term of histopathological examination. In detail, 24 rabbits were randomly divided into three groups: Group A, PEEK scaffolds; Group B, 20% CuBG/PEEK composite scaffolds; Group C, 40% CuBG/PEEK composite scaffolds; the rabbits were sacrificed at week 4 and week 12, followed by histochemical staining and observation. As a result, the PEEK group exhibited poor material exposure and tissue healing, while the CuBG/PEEK scaffolds showed good biocompatibility, and the 40% CuBG/PEEK composite scaffold exhibited the best performance in angiogenesis and tissue repair. Therefore, this study demonstrates the potential of CuBG/PEEK composite scaffolds as an orbital enucleation implant.

Stereocomplexation Reinforced High Strength Poly(L-lactide)/Nanohydroxyapatite Composites for Potential Bone Repair Applications.

Composite materials composed of polylactide (PLA) and nano-hydroxyapatite (n-HA) have been recognized as excellent candidate material in bone repai The difference in hydrophilicity/hydrophobicity and poor interfacial compatibility between n-HA filler and PLA matrix leads to non-uniform dispersion of n-HA in PLA matrix and consequent poor reinforcement effect. In this study, an HA/PLA nanocomposite was designed based on the surface modification of n-HA with poly(D-lactide) (PDLA), which not only can improve the dispersion of n-HA in the poly(L-lactide) (PLLA) matrix but also could form a stereocomplex crystal with the matrix PLLA at the interface and ultimately lead to greatly enhanced mechanical performance The n-HA/PLA composites were characterized by means of scanning electron microscopy, Fourier transform infrared spectroscopy, X-Ray diffraction, thermal gravity analysis, differential scanning calorimetry, and a mechanical test; in vitro cytotoxicity of the composite material as well as its efficacy in inducing osteogenic differentiation of rat bone marrow stromal cells (rMSCs) were also evaluated. Compared with those of neat PLLA, the tensile strength, Young's modulus, interfacial shear strength, elongation at break and crystallinity of the composites increased by 34%, 53%, 26%, 70%, and 17%, respectively. The adhesion and proliferation as well as the osteogenic differentiation of rMSCs on HA/PLA composites were clearly evidenced. Therefore, the HA/PLA composites have great potential for bone repai.

Encapsulation of green tea polyphenol by pH responsive, antibacterial, alginate microgels used for minimally invasive treatment of bone infection.

The treatment of bone infection requires drug carriers take large number of cargo, be antibacterial, promote proliferation and differentiation of osteoblasts. Herein, we proposed a strategy of preparing pH responsive, antibacterial, multistage structured microspheres encapsulated with green tea polyphenol used for minimally invasive treatment of bone infection. Tea polyphenol (TP) were encapsulated by porous silica nanospheres (SiO2 NSs). Then, sodium alginate (SA) microgel spheres (MSs) were prepared to encapsulate a lot of TP loaded SiO2 NSs. The outer layer of obtained TP@SiO2@SA microgel spheres were further wrapped by pH sensitive CaCO3. Mineral out-layer of the composite microspheres is used to neutralize the acidic environment caused by bacterial infection. At the same time, encapsulated TP is released pH sensitively to resist oxidative stress. Our results exhibited excellent drug delivery properties including drug loading efficiency (DLE) of 92.96% and drug loading content (DLC) of 19.62%. Besides, results demonstrated that TP@SiO2@SA@CaCO3 MSs can effectively kill Staphylococcus aureus and promote proliferation and differentiation of osteoblasts under stimulation of H2O2 at pH = 5.5.

Construction of injectable, pH sensitive, antibacterial, mineralized amino acid yolk-shell microspheres for potential minimally invasive treatment of bone infection.

INTRODUCTION: Treatment of infection within bone is difficult, and conventional surgical treatment brings intense pain to the patients physically and mentally. There is an urgent need to develop injectable nano- and/or micro-medicine for minimally invasive treatment of osteomyelitis. METHODS: In this paper, amino acid (L-lysine [Lys]) was mineralized into yolk-shell structured CaCO3 microspheres (MSs). The morphologies of the obtained MSs were investigated by scanning electron microscopy and transmission electron microscopy. The composition of CaCO3 MSs was identified by using Fourier transform infrared spectroscopy. The as-prepared CaCO3 MSs were examined with power X-ray diffraction analysis to obtain the crystallographic structure of the MSs. RESULTS: The as prepared Lys encapsulated CaCO3 MSs (Lys@CaCO3 MSs) were used as micro-drug to improve acidic environment of osteomyelitis caused by bacterial infection and promote osteoblast proliferation under oxidative stress. These pH responsive Lys@CaCO3 MSs have a drug loading efficiency of 89.8 wt % and drug loading content (DLC) of 22.3 wt %. CONCLUSION: Our results demonstrated that Lys@CaCO3 MSs can effectively kill Staphylococcus aureus and promote proliferation and differentiation of osteoblasts under stimulation of H2O2 at pH = 5.5.

Preparation of anticancer micro-medicine based on quinoline and chitosan with pH responsive release performance.

N-(2-(3-fluorobenzyl)-2H-indazol-5-yl)-2-phenyl-2H-pyrazolo[4,3-c]qui- nolin-4-amine (LZC-2b) with a quinoline structure was synthesized as an anticancer prodrug. The pH sensitive anticancer drugs obtained by a simple hydrothermal method. The interaction of chitosan (Cts) and LZC-2b is used to complete the encapsulation without any cross-linking. The obtained micromedicine (LZC-2b@Cts-MSs) has an average size of ∼980 nm. The drug loading efficiency (DLE) of LZC-2b@Cts-MSs was about 79%. In addition, drug release from LZC-2b@Cts-MSs was pH depended. At pH = 7.4, only 5.1% of loaded LZC-2b was released, while 90.3% of loaded LZC-2b was released at pH = 5.0. Cell culture results indicate that LZC-2b@Cts-MSs can be easily uptaken by KB cells. Cell viability results show that KB cells can be effectively killed by LZC-2b@Cts-MSs. Our strategy of synthesis and preparation of pH responsive LZC-2b@Cts-MSs has promising prospect in chemotherapy of oral cancer.

Promoting proliferation and differentiation of BMSCs by green tea polyphenols functionalized porous calcium phosphate.

In this article, we proposed a facile protocol to functionalize porous calcium phosphate ceramics (PCPC) using dietary tea polyphenols (TP). TP molecules was attracted and anchored by Ca2+ ions from the surface of CPC. These TP molecules modulated the nucleation and crystallization of calcium phosphate nanorods assemblies on the surface of PCPC. Our results prove that these calcium phosphate nanorods assemblies accompanies functional groups of TP make PCPC/TP effectively promote proliferation and differentiation of bone mesenchymal stem cells (BMSCs). We inferred that these calcium phosphate nanorods assemblies might change the surface microenvironment of PCPC, which is critical to promote the proliferation and differentiation of BMSCs. Compared with naked PCPC, PCPC/TP obviously increased BMP2, ErK/MAPK and JNK/MAPK level and mineralization capacity of cells (ALP level).

Fast ion transport through ultrathin shells of metal sulfide hollow nanocolloids used for high-performance energy storage.

Metal sulfide (MS, nickel sulfide/copper sulfide) hollow spheres with hierarchical, ultrathin shell structures have been constructed by a facile method. The as-formed MS hollow structures are shown to be uniform in sizes with hierarchical ultrathin shells, which could facilitate the transport of electrolyte ions. Electrochemical evaluations of the as-fabricated MS based materials as supercapacitors electrodes having high large surface area (106-124 m2 g-1) and high specific capacitances (up to 1460 F g-1) with good cycling stability (up to 94% retention after 5000 cycles), showing their potential applications in the next-generation high-performance supercapacitors used for energy storage.

Preparation of core-shell structured CaCO3 microspheres as rapid and recyclable adsorbent for anionic dyes.

Core-shell structured CaCO3 microspheres (MSs) were prepared by a facile, one-pot method at room temperature. The adsorbent dosage and adsorption time of the obtained CaCO3 MSs were investigated. The results suggest that these CaCO3 MSs can rapidly and efficiently remove 99-100% of anionic dyes within the first 2 min. The obtained CaCO3 MSs have a high Brunauer-Emmett-Teller surface area (211.77 m2 g-1). In addition, the maximum adsorption capacity of the obtained CaCO3 MSs towards Congo red was 99.6 mg g-1. We also found that the core-shell structured CaCO3 MSs have a high recycling capability for removing dyes from water. Our results demonstrate that the prepared core-shell structured CaCO3 MSs can be used as an ideal, rapid, efficient and recyclable adsorbent to remove dyes from aqueous solution.

Preparation of Nickel Cobalt Sulfide Hollow Nanocolloids with Enhanced Electrochemical Property for Supercapacitors Application.

Nanostructured functional materials with hollow interiors are considered to be good candidates for a variety of advanced applications. However, synthesis of uniform hollow nanocolloids with porous texture via wet chemistry method is still challenging. In this work, nickel cobalt precursors (NCP) in sub-micron sized spheres have been synthesized by a facile solvothermal method. The subsequent sulfurization process in hydrothermal system has changed the NCP to nickel cobalt sulfide (NCS) with porous texture. Importantly, the hollow interiors can be tuned through the sulfurization process by employing different dosage of sulfur source. The derived NCS products have been fabricated into supercapacitor electrodes and their electrochemical performances are measured and compared, where promising results were found for the next-generation high-performance electrochemical capacitors.