Fe-doped mesoporous silica catalyzes ascorbic acid oxidation for tumor-specific therapy in scaffold.

Ascorbic acid (AA) is a promising antitumor agent, yet its autooxidation is too slow which constrains the further application. Fortunately, the autoxidation process can be accelerated by transition metal catalysts, especially Fe3+ ions. In this study, AA was loaded to Fe-doped mesoporous silica (designated as AA@Fe-SiO2), which was introduced into poly-L-lactic acid (PLLA) and then prepared into a scaffold. Mechanistically, AA@Fe-SiO2 degraded in acidic tumor microenvironment because excessive H+ substituted Fe atoms in the iron silicate framework, releasing Fe3+ and AA. The Fe3+ boosted the pro-oxidation reaction of AA, generating numerous hydrogen peroxide (H2O2) and Fe2+. Then, Fe2+ reacted with H2O2 to initiate Fenton reactions favoring hydroxyl radical generation, triggering oxidative damage on tumor cells to implement tumor-specific therapy. Results showed that the release amount of AA in acidic solution was about 3 times higher than that in neutral solution, which was attributed to the pH-dependency of the degradation of AA@Fe-SiO2 in scaffold. Furthermore, the scaffold generated numerous ascorbate radical intermediate and increased the H2O2 concentration by 120.2%, demonstrating that Fe3+ remarkably accelerated the oxidation rate of AA. Cell experimental results showed that the scaffold caused massive apoptosis of tumor cells, while no obvious cytotoxicity to normal cells, confirming the antitumor specificity of scaffold. This work paves a promising way to construct a biodegradable and catalytic scaffold, featuring effective tumor-specific therapy.

Accelerated anode and cathode reaction due to direct electron uptake and consumption by manganese dioxide and titanium dioxide composite cathode in degradation of iron composite.

The movement towards the clinical application of iron (Fe) has been hindered by the slow degradation rate in physiological environments. Herein, manganese dioxide (MnO2) particles were compounded with titanium dioxide (TiO2) particles by mechanical ball milling, and then the mixed powders were incorporated into Fe and fabricated into an implant using selective laser melting. On the one hand, MnO2 had a higher work function (5.21 eV) than Fe (4.48 eV), which inclined electrons to transfer from Fe to MnO2 to accelerate the anode reaction. On the other hand, MnO2 catalysed the oxygen reduction reaction (ORR) through a four-step proton-electron-coupled reaction, which caused more oxygen to flow into the sample to improve the cathode performance. Besides, anatase TiO2 with high conductivity was compounded with MnO2 to construct a composite cathode, which facilitated electron transport from the cathode to the electrolyte, further consuming electrons and promoting cathode reaction. Results showed that Fe-MnO2-TiO2 had a high limiting current density of 5.32 mA·cm-2 and a large half-wave potential of -767.4 mV, indicating an enhanced ORR activity. More significantly, Fe-MnO2-TiO2 had a higher average electron transfer number (2.9) than Fe-MnO2 (2.5), demonstrating a faster electronic consumption reaction and higher cathode performance. In addition, the Fe-MnO2-TiO2 also exhibited fast instantaneous and long-term degradation rates (0.33 ± 0.03 and 0.19 ± 0.02 mm/year), suggesting a high anode dissolution rate. In conclusion, introducing the cathode with high work function and ORR activity provides novel pathways for accelerating the degradation rate of Fe-based implants.

Highly Dispersed Cu Produced by Mechanical Stress-Activated Redox Reaction to Establish Galvanic Corrosion in Fe Implant.

Fe has immense potential for biodegradable orthopedic applications, but it degrades slowly in the physiological environment. Inducing galvanic couple by alloying Cu to Fe using ball milling is a promising approach. However, the ductile nature of Cu leads to the cold welding of a large amount of Cu powder during ball milling, which makes it difficult to disperse uniformly in the Fe matrix. Here, a Fe-CuO implant with highly dispersed Cu particles in the matrix was developed by shift-speed ball milling and selective laser melting. Specifically, copper oxide (CuO) particles were selected as precursors and dispersed in Fe powders by ball milling since they were brittle and would not be cold-welded during ball milling. After further milling in higher energy, it was found that CuO particles reacted with Fe and generated Cu particles through a stress-activated redox reaction. Subsequently, the obtained powders were prepared into a Fe-CuO implant using selective laser melting. Microstructure examination revealed that the Cu phases in the implant were dispersed evenly in the Fe matrix, which was considered to establish a large number of galvanic couples and aggravated the galvanic corrosion tendency. Electrochemical tests indicated that the implant had improved performance in degradation behavior in terms of high corrosion current density (22.4 µA/cm2), low corrosion resistance (1319 Ω cm2), and good degradation stability. In addition, it presented antibacterial effects against Escherichia coli and Staphylococcus aureus by diffusion mechanisms with killing rates of 90.7 and 96.7%, respectively, as well as good cytocompatibility.

Construction of magnetic nanochains to achieve magnetic energy coupling in scaffold.

BACKGROUND: Fe3O4 nanoparticles are highly desired for constructing endogenous magnetic microenvironment in scaffold to accelerate bone regeneration due to their superior magnetism. However, their random arrangement easily leads to mutual consumption of magnetic poles, thereby weakening the magnetic stimulation effect. METHODS: In this study, magnetic nanochains are synthesized by magnetic-field-guided interface co-assembly of Fe3O4 nanoparticles. In detail, multiple Fe3O4 nanoparticles are aligned along the direction of magnetic force lines and are connected in series to form nanochain structures under an external magnetic field. Subsequently, the nanochain structures are covered and fixed by depositing a thin layer of silica (SiO2), and consequently forming linear magnetic nanochains (Fe3O4@SiO2). The Fe3O4@SiO2 nanochains are then incorporated into poly l-lactic acid (PLLA) scaffold prepared by selective laser sintering technology. RESULTS: The results show that the Fe3O4@SiO2 nanochains with unique core-shell structure are successfully constructed. Meanwhile, the orderly assembly of nanoparticles in the Fe3O4@SiO2 nanochains enable to form magnetic energy coupling and obtain a highly magnetic micro-field. The in vitro tests indicate that the PLLA/Fe3O4@SiO2 scaffolds exhibit superior capacity in enhancing cell activity, improving osteogenesis-related gene expressions, and inducing cell mineralization compared with PLLA and PLLA/Fe3O4 scaffolds. CONCLUSION: In short, the Fe3O4@SiO2 nanochains endow scaffolds with good magnetism and cytocompatibility, which have great potential in accelerating bone repair.

Stress-Induced Dual-Phase Structure to Accelerate Degradation of the Fe Implant.

Fe is considered as a potential candidate for implant materials, but its application is impeded by the low degradation rate. Herein, a dual-phase Fe30Mn6Si alloy was prepared by mechanical alloying (MA). During MA, the motion of dislocations driven by the impact stress promoted the solid solution of Mn in Fe, which transformed α-ferrite into γ-austenite since Mn was an austenite-stabilizing element. Meanwhile, the incorporation of Si decreased the stacking fault energy inside austenite grains, which tangled dislocations into stacking faults and acted as nucleation sites for ε-martensite. Resultantly, Fe30Mn6Si powder had a dual-phase structure composed of 53% γ-austenite and 47% ε-martensite. Afterward, the powders were prepared into implants by selective laser melting. The Fe30Mn6Si alloy had a more negative corrosion potential of -0.76 ± 0.09 V and a higher corrosion current of 30.61 ± 0.41 µA/cm2 than Fe and Fe30Mn. Besides, the long-term weight loss tests also proved that Fe30Mn6Si had the optimal degradation rate (0.25 ± 0.02 mm/year).

Rivet-Inspired Modification of Carbon Nanotubes by In Situ-Reduced Ag Nanoparticles To Enhance the Strength and Ductility of Zn Implants.

Zinc shows promise for bone repair applications, while its strength and ductility require to be improved. Carbon nanotubes (CNTs) are exceptional reinforcements due to their superior strength, ultrahigh Young's modulus, and large aspect ratio. However, their strong agglomeration and weak interfacial bonding with the matrix are key bottleneck problems restricting the reinforcing effect. In this study, Ag nanoparticles were in situ reduced on CNTs and then the CNT@Ag powders were used to prepare Zn-CNT@Ag implants by laser powder bed fusion. Results showed that Ag reacted with Zn to form a "knot"-like AgZn3 phase. It had the same lattice structure (HCP) with Zn, which indicated a good lattice matching with the matrix, thus improving the dispersion of CNTs. More significantly, the knot played a "rivet" role and enhanced the load transfer capacity, which advantaged the CNT strengthening effects by assisting in transferring the load. Moreover, it enhanced the heterogeneous nucleation effects during solidification, which weakened the texture strength of the matrix and thus increased the ductility by improving the sliding capacity. The compressive yield strength, ultimate tensile strength, and elongation of the Zn-CNT@Ag implant were increased by 22, 26, and 17% in comparison to Zn-CNTs. Moreover, the Zn-CNT@Ag implant exhibited favorable antibacterial activity with a bacterial inhibition rate of 87.79%. Additionally, it also exhibited a suitable degradation rate and acceptable biocompatibility.

Microstructure evolution and texture tailoring of reduced graphene oxide reinforced Zn scaffold.

Zinc (Zn) possesses desirable degradability and favorable biocompatibility, thus being recognized as a promising bone implant material. Nevertheless, the insufficient mechanical performance limits its further clinical application. In this study, reduced graphene oxide (RGO) was used as reinforcement in Zn scaffold fabricated via laser additive manufacturing. Results showed that the homogeneously dispersed RGO simultaneously enhanced the strength and ductility of Zn scaffold. On one hand, the enhanced strength was ascribed to (i) the grain refinement caused by the pinning effect of RGO, (ii) the efficient load shift due to the huge specific surface area of RGO and the favorable interface bonding between RGO and Zn matrix, and (iii) the Orowan strengthening by the homogeneously distributed RGO. On the other hand, the improved ductility was owing to the RGO-induced random orientation of grain with texture index reducing from 20.5 to 7.3, which activated more slip systems and provided more space to accommodate dislocation. Furthermore, the cell test confirmed that RGO promoted cell growth and differentiation. This study demonstrated the great potential of RGO in tailoring the mechanical performance and cell behavior of Zn scaffold for bone repair.

Electrostatic self-assembly of pFe3O4 nanoparticles on graphene oxide: A co-dispersed nanosystem reinforces PLLA scaffolds.

Cell responses and mechanical properties are vital for scaffold in bone regeneration. Fe3O4 nanoparticles with excellent magnetism can provide magnetic stimulation for cell growth, while graphene oxide (GO) nanosheets are commonly used as reinforcement phases due to their high strength. However, Fe3O4 or GO is tended to agglomerate in matrix. In present study, a novel co-dispersed Fe3O4-GO nanosystem was constructed through electrostatic self-assembly of positively charged Fe3O4 (pFe3O4) on negatively charged GO nanosheets. In the nanosystem, pFe3O4 nanoparticles and GO nanosheets support each other, which effectively alleviates the π-π stacking between GO nanosheets and magnetic attraction between pFe3O4 nanoparticles. Subsequently, the nanosystem was incorporated into poly L-lactic acid (PLLA) scaffolds fabricated using selective laser sintering. The results confirmed that the pFe3O4-GO nanosystem exhibited a synergistic enhancement effect on stimulating cell responses by integrating the capturing effect of GO and the magnetic simulation effect of pFe3O4. The activity, proliferation and differentiation of cells grown on scaffolds were significantly enhanced. Moreover, the nanosystem also exhibited a synergistic enhancement effect on mechanical properties of scaffolds, since the pFe3O4 loaded on GO improved the efficiency of stress transfer in matrix. The tensile stress and compressive strength of scaffolds were increased by 67.1% and 132%, respectively. In addition, the nanosystem improved the degradation capability and hydrophilicity of scaffolds.

Functionalized BaTiO3 enhances piezoelectric effect towards cell response of bone scaffold.

Piezoelectric effect of polyvinylidene fluoride (PVDF) plays a crucial role in restoring the endogenous electrical microenvironment of bone tissue, whereas more ß phase in PVDF leads to higher piezoelectric performance. Nanoparticles can induce the nucleation of the ß phase. However, they are prone to aggregate in PVDF matrix, resulting in weakened nucleation ability of ß phase. In this work, the hydroxylated BaTiO3 nanoparticles were functionalized with polydopamine to promote their dispersion in PVDF scaffolds fabricated via selective laser sintering. On one hand, the catechol groups of polydopamine could form hydrogen bonding with the hydroxyl groups of the BaTiO3. On the other hand, the amino groups of polydopamine were able to bond with CF group of PVDF. As a result, the functionalized BaTiO3 nanoparticles homogeneously distributed in PVDF matrix, which significantly increased the ß phase fraction from 46% to 59% with an enhanced output voltage by 356%. Cell testing confirmed the enhanced surface electric cues significantly promoted cell adhesion, proliferation and differentiation. Furthermore, the scaffolds exhibited enhanced tensile strength and modulus, which was ascribed to the rigid particle strengthening effect and the improved interfacial adhesion. This study suggested that the piezoelectric scaffolds shown a potential application in bone repair.

A continuous net-like eutectic structure enhances the corrosion resistance of Mg alloys.

Mg alloys degrade rather rapidly in a physiological environment, although they have good biocompatibility and favorable mechanical properties. In this study, Ti was introduced into AZ61 alloy fabricated by selective laser melting, aiming to improve the corrosion resistance. Results indicated that Ti promoted the formation of Al-enriched eutectic α phase and reduced the formation of ß-Mg17Al12 phase. With Ti content reaching to 0.5 wt.%, the Al-enriched eutectic α phase constructed a continuous net-like structure along the grain boundaries, which could act as a barrier to prevent the Mg matrix from corrosion progression. On the other hand, the Al-enriched eutectic α phase was less cathodic than ß-Mg17Al12 phase in AZ61, thus alleviating the corrosion progress due to the decreased potential difference. As a consequence, the degradation rate dramatically decreased from 0.74 to 0.24 mg·cm-2·d-1. Meanwhile, the compressive strength and microhardness were increased by 59.4% and 15.6%, respectively. Moreover, the Ti-contained AZ61 alloy exhibited improved cytocompatibility. It was suggested that Ti-contained AZ61 alloy was a promising material for bone implants application.

Mechanism for corrosion protection of ß-TCP reinforced ZK60 via laser rapid solidification.

It remains the primary issue to enhance the corrosion resistance of Mg alloys for their clinical applications. In this study, ß-tricalcium phosphate (ß-TCP) was composited with Mg-6Zn-1Zr (ZK60) using laser rapid solidification to improve the degradation behavior. Results revealed rapid solidification effectively restrained the aggregation of ß-TCP, which thus homogenously distributed along grain boundaries of α-Mg. Significantly, the uniformly distributed ß-TCP in the matrix promoted the formation of apatite layer on the surface, which contributed to the formation of a compact corrosion product layer, hence retarding the further degradation. Furthermore, ZK60/8ß-TCP (wt. %) composite showed improved mechanical strength, as well as improved cytocompatibility. It was suggested that laser rapidly solidified ZK60/8ß-TCP composite might be a potential materials for tissue engineering.

Regulating Degradation Behavior by Incorporating Mesoporous Silica for Mg Bone Implants.

Magnesium (Mg) alloys are potential bone implant materials because of their natural biodegradability, good biocompatibility and suitable mechanical properties. However, the too rapid degradation in physiological environment has delayed their introduction for orthopedic applications to date. To improve the degradation behavior, mesoporous silica (MS) was incorporated into ZK60 (Mg-6Zn-0.5Zr, wt %) via selective laser melting technology. Results showed that MS homogeneously incorporated in Mg matrix with good bonding interface. MS was chemical inert against Mg and shifted the corrosion potential positively, indicating an enhanced corrosion resistance. Moreover, MS promoted the deposition of apatite on surface and formed a compact protection layer, thus effectively preventing the further corrosion of Mg matrix. As a result, the degradation rate was reduced by 57%, with MS containing up to 8 wt %. In addition, ZK60/8MS composite exhibited improved biocompatibility. It was suggested the ZK60/8MS composite with improved degradation behavior and good biocompatibility was a potential candidate biomaterial for the bone implants.

Biodegradation Resistance and Bioactivity of Hydroxyapatite Enhanced Mg-Zn Composites via Selective Laser Melting.

Mg-Zn alloys have attracted great attention as implant biomaterials due to their biodegradability and biomechanical compatibility. However, their clinical application was limited due to the too rapid degradation. In the study, hydroxyapatite (HA) was incorporated into Mg-Zn alloy via selective laser melting. Results showed that the degradation rate slowed down due to the decrease of grain size and the formation of protective layer of bone-like apatite. Moreover, the grain size continually decreased with increasing HA content, which was attributed to the heterogeneous nucleation and increased number of nucleation particles in the process of solidification. At the same time, the amount of bone-like apatite increased because HA could provide favorable areas for apatite nucleation. Besides, HA also enhanced the hardness due to the fine grain strengthening and second phase strengthening. However, some pores occurred owing to the agglomerate of HA when its content was excessive, which decreased the biodegradation resistance. These results demonstrated that the Mg-Zn/HA composites were potential implant biomaterials.