Nanotube-decorated hierarchical tantalum scaffold promoted early osseointegration.

This study aimed to fabricate a hierarchical tantalum scaffold mimicking natural bone structure to enhance osseointegration. Porous tantalum scaffolds (p-Ta) with microgradients were fabricated by selective laser melting according to a computer-aided design model. Electrochemical anodization produced nanotubes on the p-Ta surface (p-Ta-nt). SEM verified the construction of a unique nanostructure on p-Ta-nt. Contact angle and protein adsorption measurements demonstrated that p-Ta-nt have enhanced hydrophilicity and protein absorption. MC3T3-E1 preosteoblasts showed increased filamentous pseudopods and comparable cell proliferation when cultured on p-Ta-nt. Osteogenic marker gene (Osterix, Runx2, COL-I) transcription was significantly upregulated in MC3T3-E1 cells cultured on p-Ta-nt after 7 days. After implantation into the femurs of New Zealand white rabbits for 2 weeks, histological examination found improved early osseointegration in the p-Ta-nt group. This study showed that a hierarchical tantalum structure could enhance early osteogenic effects in vitro and in vivo.

Mn-Based Artificial Mitochondrial Complex "VI" Acts as an Electron and Free Radical Conversion Factory to Suppress Macrophage Inflammatory Response.

Disturbance in the mitochondrial electron transport chain (ETC) is a key factor in the emerging discovery of immune cell activation in inflammatory diseases, yet specific regulation of ETC homeostasis is extremely challenging. In this paper, a mitochondrial complex biomimetic nanozyme (MCBN), which plays the role of an artificial "VI" complex and acts as an electron and free radical conversion factory to regulate ETC homeostasis is creatively developed. MCBN is composed of bovine serum albumin (BSA), polyethylene glycol (PEG), and triphenylphosphine (TPP) hierarchically encapsulating MnO2 polycrystalline particles. It has nanoscale size and biological properties like natural complexes. In vivo and in vitro experiments confirm that MCBN can target the mitochondrial complexes of inflammatory macrophages, absorb excess electrons in ETC, and convert the electrons to decompose H2O2. By reducing the ROS and ATP bursts and converting existing free radicals, inhibiting NLRP3 inflammatory vesicle activation and NF-κB signaling pathway, MCBN effectively suppresses macrophage M1 activation and inflammatory factor secretion. It also demonstrates good inflammation control and significantly alleviates alveolar bone loss in a mouse model of ligation-induced periodontitis. This is the first nanozyme that mimics the mitochondrial complex and regulates ETC, demonstrating the potential application of MCBN in immune diseases.

[Preparation and performance evaluation of fast dissolving polymer microneedles piggybacked with sitagliptin].

The dramatic rise in the number of obese/overweight people is a global public health challenge that urgently requires novel and effective therapies. In this study, we designed a fast dissolving polymer microneedle array patch (SGN-PVP/PVA-MN) with sitagliptin as a model drug for treating obesity, focusing on the preparation process of the patch. We then characterized the morphology and dimensions of SGN-PVP/PVA-MN. Furthermore, we delved into the mechanical properties, solubility, skin-puncturing capability, and transdermal drug diffusion and release kinetics of SGN-PVP/PVA-MN. The results demonstrated that SGN-PVP/PVA-MN exhibited favorable morphology and mechanical properties, effectively penetrating the stratum corneum and creating microchannels for rapid transdermal drug diffusion. The in vitro transdermal diffusion assays revealed the release of 64.5% of the drug within 2 min and 95.7% within 10 min. With rapid dissolution and high drug diffusion efficiency, SGN-PVP/PVA-MN is poised to serve as an effective and safe treatment option for the individuals with obesity.

Shape memory luminescent cellulose/chitosan hydrogel for high sensitive detection of formaldehyde.

Hybrid hydrogels containing biomacromolecules have been widely used in sensors, fluorescent probes, and other fields due to their high biocompatibility and nontoxicity. In this paper, tough hydrogels with interconnected macro-pores have been fabricated by freeze-induced chemical cross-linking of microfibrillated cellulose (MFC) and organic modified chitosan (CS). In this hydrogel materials, three-dimensional networks were formed by abundant hydrogen bonds and chemical cross-linking. Luminescent lanthanide complexes were covalently bonded to the hydrogel networks through coordination of Eu3+ ions with 2, 3-pyridine dicarboxylic acid modified chitosan. The luminescence of hydrogel materials was further improved by the replacement of coordination water with 2-thiophenyltrifluoroacetone (TTA). The prepared hydrogels showed excellent shape memory properties both under water and in air. The stress of the hybrid hydrogel at 80 % strain can reach 159 kPa, which is much higher than that of the traditional microfibrillated cellulose-based hydrogels. The obtained luminescent hybrid hydrogels exhibited an excellent fluorescence detection effect on formaldehyde. The detection limit for formaldehyde is 45.7 ppb, which is much lower than the WHO standard (80 ppb for indoor air). The novel, facile preparing procedure may extend the potential applications of hybrid lanthanide luminescent hydrogel as fluorescence probes for pollution monitoring, especially for formaldehyde and other organic aldehydes.

Mitochondrial Calcium Ion Nanogluttons Alleviate Periodontitis via Controlling mPTPs.

The mitochondrial permeability transition (mPT) directly affects mitochondrial function in macrophages. Under inflammatory conditions, mitochondrial calcium ion (mitoCa2+ ) overload triggers the persistent opening of mPT pores (mPTPs), further aggravating Ca2+ overload and increasing reactive oxygen species (ROS) to form an adverse cycle. However, there are currently no effective drugs targeting mPTPs to confine or unload excess Ca2+ . It is novelly demonstrated that the initiation of periodontitis and the activation of proinflammatory macrophages depend on the persistent overopening of mPTPs, which is mainly triggered by mitoCa2+ overload and facilitates further mitochondrial ROS leakage into the cytoplasm. To solve the above problems, mitochondrial-targeted "nanogluttons" with PEG-TPP conjugated to the surface of PAMAM and BAPTA-AM encapsulated in the core are designed. These nanogluttons can efficiently "glut" Ca2+ around and inside mitochondria to effectively control the sustained opening of mPTPs. As a result, the nanogluttons significantly inhibit the inflammatory activation of macrophages. Further studies also unexpectedly reveal that the alleviation of local periodontal inflammation in mice is accompanied by diminished osteoclast activity and reduced bone loss. This provides a promising strategy for mitochondria-targeted intervention in inflammatory bone loss in periodontitis and can be extended to treat other chronic inflammatory diseases associated with mitoCa2+ overload.

Three-Dimensional Matrix Stiffness Activates the Piezo1-AMPK-Autophagy Axis to Regulate the Cellular Osteogenic Differentiation.

Extracellular matrix (ECM) stiffness is a key stimulus affecting cellular differentiation, and osteoblasts are also in a three-dimensional (3D) stiff environment during the formation of bone tissues. However, it remains unclear how cells perceive matrix mechanical stiffness stimuli and translate them into intracellular signals to affect differentiation. Here, for the first time, we constructed a 3D culture environment by GelMA hydrogels with different amino substitution degrees and found that Piezo1 expression was significantly stimulated by the stiff matrix with high substitution; meanwhile, the expressions of osteogenic markers OSX, RUNX2, and ALP were also observably improved. Moreover, knockdown of Piezo1 in the stiff matrix revealed significant reduction of the abovementioned osteogenic markers. In addition, in this 3D biomimetic ECM, we also observed that Piezo1 can be activated by the static mechanical conditions of the stiff matrix, leading to the increase of the intracellular calcium content and accompanied with a continuous change in cellular energy levels as ATP was consumed during cellular differentiation. More surprisingly, we found that in the 3D stiff matrix, intracellular calcium as a second messenger promoted the activation of the AMP-activated protein kinase (AMPK) and unc-51-like autophagy-activated kinase 1 (ULK1) axis and modestly modulated the level of autophagy, bringing it more similar to differentiated osteoblasts, with increased ATP energy metabolism consumption. Our study innovatively clarifies the regulatory role of the mechanosensitive ion channel Piezo1 in a static mechanical environment on cellular differentiation and verifies the activation of the AMPK-ULK1 axis in the cellular ATP energy metabolism and autophagy level. Collectively, our research develops the understanding of the interaction mechanisms of biomimetic extracellular matrix biomaterials and cells from a novel perspective and provides a theoretical basis for bone regeneration biomaterials design and application.

Novel and wet-resilient cellulose nanofiber cryogels with tunable porosity and improved mechanical strength for methyl orange dyes removal.

Interconnected macro-porous cryogels with robust and pore-tunable structures have been fabricated using chemically crosslinked microfibrillated cellulose (MFC). Periodate oxidation was initially conducted to introduce aldehyde groups into the MFC surface, followed by the freeze-induced chemical crosslinking via the formation of hemiacetal bonds between aldehyde and hydroxyl at -12 °C. The cryogels with pore-tunable structures and sharply enhanced mechanical strengths were finally achieved by re-assembly of MFCs through soaking in NaIO4 solution. Furthermore, the MFC cryogels were post-crosslinked by polyethyleneimine (PEI), bestowing the cryogels with the capability of adsorbing anionic dyes. The stress of the PEI-MFC cryogel at the 80% strain was determined to be 304.5 kPa, which is the maximum value for the nanocellulose-based cryogels reported so far. Finally, the adsorption performances of PEI-MFC cryogels for methyl orange (MO) were evaluated. Maximum adsorption capacity of 500 mg/g could be obtained by the Langmuir model, outperforming that of previous absorbent materials. Reuse experiments indicated that over 90% of adsorption capacity was retained after 6 cycles. Continuous clean-up experiments demonstrated excellent MO removal abilities of the PEI-MFC cryogel. This study shows that the novel, green strategy to fabricate the robust cryogel extends the practical applications of nanocellulose adsorbents for environmental remediation.

Synthesis and crystal structures of two coordination polymers and a binuclear cadmium(II) complex containing 3- and 4-aminobenzoate ligands.

Due to their wide range of coordination modes and versatile conformations when binding to metal atoms, multicarboxylate ligands are of interest in the design of metal-organic frameworks (MOFs). Three Cd(II) complexes, namely catena-poly[diammonium [[chloridocadmium(II)]-di-µ-chlorido-[chloridocadmium(II)]-bis(µ-3-aminobenzoato)-κ(3)N:O,O';κ(3)O,O':N]], {(NH4)[CdCl2(C7H6NO2)]}n, (I), catena-poly[[[aquacadmium(II)]-bis(µ-4-aminobenzoato)-κ(3)N:O,O';κ(3)O,O':N] monohydrate], {[Cd(C7H6NO2)2(H2O)]·H2O}n, (II), and di-µ-acetato-κ(4)O:O'-bis[(4-aminobenzoato-κ(2)O,O')(2,2'-bipyridine-κ(2)N,N')cadmium(II)], [Cd2(CH3COO)2(C7H6NO2)2(C10H8N2)2], (III), with different stuctural forms are reported. Complex (I) has a one-dimensional ladder structure, with strong N-H···O and weak N-H···Cl hydrogen bonds linking the cations and anions in the three-dimensional supramolecular structure. Complex (II) has a one-dimensional chain structure. Extensive O-H···O and N-H···O hydrogen bonds between the anionic ligands and the solvent water molecules and π-π stacking interactions between the centroids of the benzene rings lead to the three-dimensional supramolecular structure. Complex (III) is a binuclear molecule which is extended into a three-dimensional supramolecular structure via strong N-H···O and weak C-H···O hydrogen bonds.