Mineralization, degradation and osteogenic property of polylactide multicomponent porous composites for bone repair: In vitro and in vivo study.

Gelatin and hydroxyapatite were assembled into polylactide porous matrix to prepare multicomponent porous composites for bone repair (PLA-gH). PLA-gH possessed a superior ability of mineralization. During simulated body fluids (SBF), the spherical Ca-P depositions on surface of PLA-gH became bulk as Ca/P decreased, while they locally turned into the rod with different variation in Ca/P during SBF containing bovine serum albumin (SBF-BSA), indicating that the mineralization of PLA-gH could be regulated by BSA. Meanwhile, PLA-gH possessed good degradation behaviour, especially in SBF-BSA, the degradation of PLA porous matrix was higher than that in SBF after 14-day immersion, whose crystallinity (Xc) decreased to a slightly lower level. Gelatin and hydroxyapatite endowed PLA-gH with good osteogenic property, characterized by obvious osteogenic differentiation and bone regeneration. In terms of predicting the cytocompatibility, osteogenic differentiation and new bone mineralization of PLA-gH by in vitro methods, applying SBF-BSA may be more reliable than SBF.

NIR-responsive magnesium phosphate cement loaded with simvastatin-nanoparticles with biocompatibility and osteogenesis ability.

The insufficient osteogenesis of magnesium phosphate cement (MPC) limits its biomedical application. It is of great significance to develop a bioactive MPC with osteogenic performance. In this study, an injectable MPC was reinforced by the incorporation of a near infrared (NIR)-responsive nanocontainer, which was based on simvastatin (SIM)-loaded mesoporous silica nanoparticles (MSNs) modified with a polydopamine (PDA) bilayer, named SMP. In addition, chitosan (CHI) was introduced into MPC (K-struvite) to enhance its mechanical properties and cytocompatibility. The results showed that nanocontainer-incorporated MPC possessed a prolonged setting time, almost neutral pH, excellent injectability, and enhanced compressive strength. Immersion tests indicated that SMP-CHI MPC could suppress rapid degradation. Based on its physicochemical features, the SMP-CHI MPC had good biocompatibility and osteogenesis properties, as shown via in vitro and in vivo experiments. These findings can provide a simple way to produce a multifunctional MPC with improved osteogenesis for further orthopedic applications.

An Injectable Magnesium-Based Cement Stimulated with NIR for Drug-Controlled Release and Osteogenic Potential.

Magnesium phosphate bone cement (MPC) has gained widespread usage in orthopedic implantation due to its fast-setting and high initial strength benefits. However, the simultaneous attainment of drug-controlled release and osteogenic potential in MPC remains a significant challenge. Herein, a strategy to create a smart injectable cement system using nanocontainers and chondroitin sulfate is proposed. It employs nanocontainers containing alendronate-loaded mesoporous silica nanoparticles, which are surface-modified with polypyrrole to control drug release in response to near-infrared (NIR) stimulation. The alendronate-incorporated cement (ACMPC) exhibits improved compressive strength (70.6 ± 5.9 MPa), prolonged setting time (913 s), and exceptional injectability (96.5% of injection rate and 242 s of injection time). It also shows the capability to prevent degradation, thus preserving mechanical properties. Under NIR irradiation, the cement shows good antibacterial properties due to the combined impact of hyperthermia, reactive oxygen species, and alendronate. Furthermore, the ACMPC (NIR) group displays good biocompatibility and osteogenesis capabilities, which also lead to an increase in alkaline phosphatase activity, extracellular matrix mineralization, and the upregulation of osteogenic genes. This research has significant implications for developing multifunctional biomaterials and clinical applications.

Porous Mg-Zn-Ca scaffolds for bone repair: a study on microstructure, mechanical properties and in vitro degradation behavior.

Biodegradable porous Mg scaffolds are a promising approach to bone repair. In this work, 3D-spherical porous Mg-1.5Zn-0.2Ca (wt.%) scaffolds were prepared by vacuum infiltration casting technology, and MgF2 and fluorapatite coatings were designed to control the degradation behavior of Mg-based scaffolds. The results showed that the pores in Mg-based scaffolds were composed of the main spherical pores (450-600 µm) and interconnected pores (150-200 µm), and the porosity was up to 74.97%. Mg-based porous scaffolds exhibited sufficient mechanical properties with a compressive yield strength of about 4.04 MPa and elastic modulus of appropriately 0.23 GPa. Besides, both MgF2 coating and fluorapatite coating could effectively improve the corrosion resistance of porous Mg-based scaffolds. In conclusion, this research would provide data support and theoretical guidance for the application of biodegradable porous Mg-based scaffolds in bone tissue engineering.

pH-responsive, self-sculptured Mg/PLGA composite microfibers for accelerated revascularization and soft tissue regeneration.

Biodegradable Mg/polymer composite fibers offer a promising therapeutic option for tissue injury because of bioactive Mg2+ and biomimetic microstructure. However, current studies are limited to the contribution of Mg2+ and the single microstructure. In this study, we designed Mg/poly (lactic-co-glycolic acid) (Mg/PLGA) composite microfibers that significantly enhanced angiogenesis and tissue regeneration synergistically by Mg2+ and self-sculptured microstructure, due to spontaneous in situ microphase separation in response to the weakly alkaline microenvironment. Our composite microfiber patch exhibited superior performance in the adhesion, spreading, and angiogenesis functions of human umbilical vein endothelial cells (HUVECs) due to the joint contribution of the hierarchically porous microstructure and Mg2+. Genomics and proteomics analyses revealed that the Mg/PLGA composite microfibers activated the cell focal adhesion and angiogenesis-related signaling pathways. Furthermore, the repair of typical soft tissue defects, including refractory urethral wounds and easily healed skin wounds, validated that our Mg/PLGA composite microfiber patch could provide favorable surface topography and ions microenvironment for tissue infiltration and accelerated revascularization. It could cause rapid urethral tissue regeneration and recovery of rabbit urethral function within 6 weeks and accelerate rat skin wound closure within 16 days. This work provides new insight into soft tissue regeneration through the bioactive alkaline substance/block copolymer composites interactions.

Self-Assembled Multilayered Coatings with Multiple Cyclic Self-Healing Capability, Bacteria Killing, Osteogenesis, and Angiogenesis Properties on Magnesium Alloys.

Self-healing coatings improve the durability of magnesium (Mg) implants, but rapid corrosion still poses a challenge in the healing stage. Moreover, Mg-based materials with acceptable bacteria killing, osteogenic and angiogenic properties are challenging in biomedical applications. Herein, the self-healing polymeric coatings are fabricated on Mg alloys using the spin-assisted layer-by-layer (SLbL) assembly of hyaluronic acid (HA) and branched polyethyleneimine (bPEI) followed by chemical crosslinking treatment. The self-healing coatings show excellent adhesion strength and structure stability. The corrosion resistance is improved due to the physical barrier of polymer coatings, which also promotes the formation of hydroxyapatite (HAp) during degradation for further protection of Mg substrate. Owing to the dynamic reversible hydrogen bonds existing between HA and bPEI, the crosslinked multilayered coatings possess fast, substantial, and cyclic self-healing capabilities leading to restoration of the original structure and functions. In vitro investigations reveal that the self-healing coatings have multiple functionalities pertaining to bacteria killing, cytocompatibility, osteogenesis, as well as angiogenesis. In addition, the self-healing coatings stimulate alkaline phosphatase activity (ALP), extracellular matrix (ECM) mineralization, and the expression of osteogenesis-related genes of mBMSCs and HUVECs. This study reveals a feasible strategy to design and prepare versatile self-healing coatings on Mg implants for biomedical applications.

Dual Mg-Reinforced PCL Membrane with a Janus Structure for Vascularized Bone Regeneration and Bacterial Elimination.

Commercially available guided bone regeneration (GBR) membranes often exhibit limited mechanical properties or bioactivity, leading to poor performance in repairing bone defects. To surmount this limitation, we developed a Janus structural composite membrane (Mg-MgO/PCL) reinforced by dual Mg (Mg sheets and MgO NPs) by using a combined processing technique involving casting and electrospinning. Results showed that the addition of Mg sheets and MgO NPs enhanced the mechanical properties of the composite membrane for osteogenic space maintenance, specifically tensile strength (from 10.2 ± 1.2 to 50.3 ± 4.5 MPa) and compression force (from 0 to 0.94 ± 0.09 N mm-1), through Mg sheet reinforcement and improved crystallization. The dense cast side of the Janus structure membrane displayed better fibroblast barrier capacity than a single fiber structure; meanwhile, the PCL matrix protected the Mg sheet from severe corrosion due to predeformation. The porous microfibers side supported preosteoblast cell adhesion, enhanced osteogenesis, and angiogenesis in vitro, through the biomimetic extracellular matrix and sustainable Mg2+ release. Furthermore, the Mg-MgO/PCL membrane incorporating 2 wt % MgO NPs exhibited remarkable antimicrobial properties, inducing over 88.75% apoptosis in Staphylococcus aureus. An in vivo experiment using the rat skull defect model (Φ = 5 mm) confirmed that the Mg-MgO/PCL membrane significantly improved new bone formation postsurgery. Collectively, our investigation provides valuable insights into the design of multifunctional membranes for clinical oral GBR application.

Incorporating pH/NIR responsive nanocontainers into a smart self-healing coating for a magnesium alloy with controlled drug release, bacteria killing and osteogenesis properties.

Magnesium (Mg)-based orthopedic implant materials can potentially be protected from deterioration using a protective polymer coating. However, this coating is susceptible to excessive corrosion and accidental scratches. Moreover, the inadequate bone integration and infections associated with bone implants present additional challenges that hinder their effective use. In this work, a spin-spray layer-by-layer (SSLbL) assembly technique was employed to develop a smart self-healing coating for Mg alloy WE43. This coating was based on paeonol-encapsulated nanocontainers (PMP) that were modified with a stimuli-responsive polydopamine (PDA). The leached paeonol could form a compact chelating layer when complexed with Mg2+ ions. Dynamic reversible hydrogen bonds were formed between assembly units, which ensured that the hybrid coating possessed rapid and cyclic self-healing properties. Under 808 nm near-infrared (NIR) laser irradiation, the self-healing coating exhibited antibacterial properties due to the synergistic effects of hyperthermia, reactive oxygen species (ROS), and paeonol. In addition, the incorporation of nanoparticles into the hybrid coating led to improvements in the cytocompatibility and osteogenic properties of the implant material. The smart coating enhanced alkaline phosphatase activity, extracellular matrix (ECM) mineralization, and the expression of osteogenic genes. This study presents a promising opportunity to explore the application of a smart self-healing coating for a Mg alloy. STATEMENT OF SIGNIFICANCE: Herein, we report a self-healing coating comprised of polyethyleneimine and nanocontainer-crosslinked hyaluronic acid to achieve drug-controlled release, antimicrobial activity, and osteogenesis performance. The formation of hydrogen bonds between HA and PEI facilitated the self-assembly process, thereby improving the coating's corrosion resistance and adhesion strength. The hybrid coating exhibited a rapid and cyclic self-healing activity due to paeonol and dynamic reversible bonds. The release of paeonol was controlled by pH and NIR stimuli owing to polydopamine modification. In vitro testing revealed that the hybrid coating achieved effective bacteria eradication through synergistic effects of hyperthermia, reactive oxygen species, and paeonol. Moreover, the smart coating was found to enhance alkaline phosphatase activity, extracellular matrix mineralization, and the expression of osteogenic genes.

NIR-responsive injectable magnesium phosphate bone cement loaded with icariin promotes osteogenesis.

There were defects like limited osteogenesis and fast drug release in traditional magnesium phosphate bone cement (MPC). In this study, we loaded icariin in a mesoporous nano silica container modified by polydopamine and then added it and citric acid into MPC (IHP-CA MPCs). The results indicate that IHP-CA MPCs have a long curing time, almost neutral pH value, excellent injectability, and compressive strength. In vitro experiments have shown that IHP-CA MPCs have good biocompatibility and bone promoting ability. These improvements provide feasible solutions and references for the clinical application of MPCs as implants.

pH/NIR-responsive and self-healing coatings with bacteria killing, osteogenesis, and angiogenesis performances on magnesium alloy.

Although biodegradable polymer coatings can impede corrosion of magnesium (Mg)-based orthopedic implants, they are prone to excessive degradation and accidental scratching in practice. Bone implant-related infection and limited osteointegration are other factors that adversely impact clinical application of Mg-based biomedical implants. Herein, a self-healing polymeric coating is constructed on the Mg alloy together with incorporation of a stimuli-responsive drug delivery nanoplatform by a spin-spray layer-by-layer (SSLbL) assembly technique. The nanocontainers are based on simvastatin (SIM)-encapsulated hollow mesoporous silica nanoparticles (S@HMSs) modified with polydopamine (PDA) and polycaprolactone diacrylate (PCL-DA) bilayer. Owing to the dynamic reversible reactions, the hybrid coating shows a fast, stable, and cyclical water-enabled self-healing capacity. The antibacterial assay indicates good bacteria-killing properties under near infrared (NIR) irradiation due to synergistic effects of hyperthermia, reactive oxygens species (ROS), and SIM leaching. In vitro results demonstrate that NIR laser irradiation promotes the cytocompatibility, osteogenesis, and angiogenesis. The coating facilitates alkaline phosphatase activity and expedites extracellular matrix mineralization as well as expression of osteogenesis-related genes. This study reveals a useful strategy to develop multifunctional coatings on bioabsorbable Mg alloys for orthopedic implants.

Accumulative Rolling Mg/PLLA Composite Membrane with Lamellar Heterostructure for Enhanced Bacteria Inhibition and Rapid Bone Regeneration.

Developing composite materials with optimized mechanics, degradation, and bioactivity for bone regeneration has long been a crucial mission. Herein, a multifunctional Mg/Poly-l-lactic acid (Mg/PLLA) composite membrane based on the "materials plain" concept through the accumulative rolling (AR) method is proposed. Results show that at a rolling ratio of 75%, the comprehensive mechanical properties of the membrane in the rolling direction are self-reinforced significantly (elongation at break ≈53.2%, tensile strength ≈104.0 MPa, Young's modulus ≈2.13 GPa). This enhancement is attributed to the directional arrangement and increased crystallization of PLLA molecular chains, as demonstrated by SAXS and DSC results. Furthermore, the AR composite membrane presents a lamellar heterostructure, which not only avoids the accumulation of Mg microparticles (MgMPs) but also regulates the degradation rate. Through the contribution of bioactive MgMPs and their photothermal effect synergistically, the membrane effectively eliminates bacterial infection and accelerates vascularized bone regeneration both in vitro and in vivo. Notably, the membrane exhibits outstanding rat skull bone regeneration performance in only 4 weeks, surpassing most literature reports. In short, this work develops a composite membrane with a "one stone, four birds" effect, opening an efficient avenue toward high-performance orthopedic materials.

A biodegradable magnesium surgical staple for colonic anastomosis: In vitro and in vivo evaluation.

Staplers have been widely used in the clinical treatment of gastrointestinal reconstruction. However, the current titanium (Ti) staple will remain in the human body permanently, resulting in some adverse effects. In this study, we developed a type of biodegradable staple for colonic anastomosis using 0.3 mm diameter magnesium (Mg) alloy wires. The wire surface was modified by micro-arc oxidation treatment (MAO) and then coated with poly-l-lactic acid (PLLA) to achieve a moderate degradation rate matching the tissue healing process. The results of tensile tests on isolated porcine colon tissue anastomosed by Mg and Ti staples showed that the anastomotic property of Mg staples was almost equal to that of Ti staples. The in vitro degradation tests indicated the dual-layer coating effectively enhanced the corrosion resistance and maintained the tensile force of the coated staple stable after 14-day immersion in the simulated colonic fluid (SCF). Furthermore, 24 beagle dogs were employed to conduct a comparison experiment using Mg-based and clinical Ti staples for 90-day implantation by ent-to-side anastomosis of the colon. The integrated structure of Mg-based staples was observed after 7 days and completely degraded after 90 days. All animals did not have anastomotic leakage and stenosis, and 12 dogs with Mg-based staples fully recovered after 90 days without differences in visceral ion levels and other side effects. The favorable performance makes this Mg-based anastomotic staple an ideal candidate for colon reconstruction.

AuNP/Chitosan Nanocomposites Synthesized through Plasma Induced Liquid Chemistry and Their Applications in Photothermal Induced Bacteria Eradication.

In this work, a facile direct current atmospheric pressure micro-plasma (APM) technology was deployed for the synthesis of functional gold nanoparticle/chitosan (AuNP/CS) nanocomposites for the first time. Different experimental parameters, such as metal salt precursor concentration and chitosan viscosity, have been investigated to understand their effects on the resulting nanocomposite structures and properties. The nanocomposites were fully characterized using a wide range of material characterization techniques such as UV-vis, transmission electron microscope (TEM), Fourier transform infrared (FTIR) spectra and X-ray photoelectron spectroscopy (XPS) analyses. Potential reaction pathways have been proposed for the nanocomposite synthesis process. Finally, potential of the synthesized nanocomposites towards photothermal conversion and bacteria eradiation applications has been demonstrated. The results show that APM is a facile, rapid and versatile technique for the synthesis of AuNP/CS functional nanocomposites. Through this work, a more in-depth understanding of the multi-phase system (consisting of gas, plasma, liquid and solid) has been established and such understanding could shine a light on the future design and fabrication of new functional nanocomposites deploying the APM technique.

Effects of Different Concentrations of BSA on In Vitro Corrosion Behavior of Pure Zinc in Artificial Plasma.

When medical metallic materials are implanted in the body and come into contact with the body fluid environment, proteins will be rapidly adsorbed on the surface and affect the corrosion process of the material. Currently, there is no uniform understanding of the effect of protein adsorption on the corrosion behavior of materials due to the limitations of the nature of metal materials, protein concentrations, and different media environments. The effect of various bovine serum albumin (BSA) concentrations in artificial plasma (AP) on the corrosion behavior of pure Zn during 14 days of immersion was investigated in this research. The corrosion rate of pure Zn was slowed down by the addition of BSA, and the decelerating effect of lower protein concentration on the corrosion rate of Zn was more significant in the initial stage of immersion. With prolonging the immersion time, the corrosion rate of pure Zn in different media slowed down and stabilized, and the corrosion rates of pure Zn showed a decreasing trend with an increase of BSA concentration. Furthermore, the Langmuir adsorption isotherm model was utilized to study the relationship between the BSA concentration and corrosion behavior of pure Zn and to analyze the role of proteins in the degradation mechanism of pure Zn. This work could be useful for further exploration of potential clinical applications of zinc alloys.

Effect of Cu and Mg addition on the mechanical and degradation properties of Zn alloy wires.

In this study, Zn-xCu (-0.1 Mg) wires with a diameter of 0.3 mm were obtained by hot extrusion and cold drawing. The microstructures, mechanical properties, and degradation behaviour were investigated to evaluate their feasibility as biodegradable metals. During the drawing process of the Zn-xCu alloys, many granular CuZn5 phases were dynamically precipitated, and the grains were significantly refined, along with a significant work softening with the tensile strength decreasing and the elongation increasing (from 161 MPa to 92 MPa and 22%-103% for Zn-0.2Cu). With the increase of Cu additions, the phenomenon of work softening was more intense and there was an opposite trend in the strength changes between the as-extruded rods (increase) and as-drawn wires (decrease). With 0.1 wt.% Mg added, the stable rod-like Mg2Zn11 phase was formed in as-extruded Zn-xCu-0.1 Mg rods, which obviously improved the strength, and inhibited the dynamic precipitation of granular CuZn5 phase and work softening phenomenon in the drawing process (from 332 MPa to 313 MPa and 11%-46% for Zn-0.2Cu-0.1 Mg). In addition, due to the micro-galvanic effect induced by the precipitates, alloying accelerated the degradation of Zn alloy wires, especially Zn-1Cu-0.1 Mg, which was related to the shape, distribution, and potential of the phases.

Preparation of 4D printed peripheral vascular stent and its degradation behavior under fluid shear stress after deployment.

Shape memory stents are mild intervention devices for vascular diseases as compared to balloon-dilated ones; however, their degradation behavior under blood shear stress after deployment also deserves further attention. To understand the degradation behavior, we first prepared 4D printed poly(lactic acid) (PLA) stents via 3D printing technology and studied their failure behavior in a dynamic condition after self-expandable deployment. Mechanical property tests showed that the 4D printed stents had a compression force of 0.06-0.39 N mm-1 and a recovery ratio of 85.3-93.4%, respectively, which was verified to be wall thickness dependent. The stents were then implanted in simulated blood vessels with minimal microstructural damage at 60 °C followed by 8-week degradation tests. The results showed the microstructure damage caused by deployment could accelerate the degradation of stents faster than fluid shear stress. Furthermore, we conducted microstructural analysis and numerical simulation on the stent by finite element analysis (FEA) to explain the relationship between stent injury, vascular injury, and stent deployment temperature. A physical model derived from micro-morphologies on the degradation mechanism of PLA was also proposed. These results may provide new insights for the examination of the degradation behavior of 4D printed stents and minimize medical risk.

Strengthening of CoNiFeV0.5Mo0.2 Medium Entropy Alloy Wire Rods with Loading-Unloading Cycles.

Changes in the texture as well as mechanical properties of CoNiFeV0.5Mo0.2 medium entropy alloy wire rods during loading-unloading are investigated. The intensity of the recrystallization texture {001}<110> component and fraction of low angle grains increase with the loading-unloading cycles and the alloy strength increases (934 MPa to 1083 MPa) due to dislocation increment in the loading-unloading cycles. The loading modulus (El) and average modulus (Esecant) for a hysteresis loop decrease slightly, whereas the unloading modulus (Eun) increases, the Eun increment of 5-TC-UTand 10-TC-UT are 22 and 137 GPa.

The effect of enzymes on the in vitro degradation behavior of Mg alloy wires in simulated gastric fluid and intestinal fluid.

With an upsurge of biodegradable metal implants, the research and application of Mg alloys in the gastrointestinal environment of the digestive tract have been of great interest. Digestive enzymes, mainly pepsin in the stomach and pancreatin in the small intestine, are widespread in the gastrointestinal tract, but their effect on the degradation of Mg alloys has not been well understood. In this study, we investigated the impacts of pepsin and pancreatin on the degradation of Mg-2Zn alloy wires. The results showed that the pepsin and pancreatin had completely different even the opposite effects on the degradation of Mg, although they both affected the degradation product layer. The degradation rate of Mg wire declined with the addition of pepsin in simulated gastric fluid (SGF) but rose with the addition of pancreatin in simulated intestinal fluid (SIF). The opposite trends in degradation rate also resulted in completely different degradation morphologies in wires surface, where the pitting corrosion in SGF was inhibited because of the physical barrier effect of pepsin adsorption. In contrast, the adsorption of pancreatin affected the integrity of magnesium hydrogen phosphate film, causing a relatively uneven degraded surface. These results may help us to understand the role of different digestive enzymes in the degradation of magnesium and facilitate the development and clinical application of magnesium alloy implanted devices for the digestive tract.

The influence of alternating cyclic dynamic loads with different low frequencies on the bio-corrosion behaviors of AZ31B magnesium alloy in vitro.

The real physiological environment of human body is complicated with different degrees and forms of dynamic loads applied to implanted medical devices due to the daily activities of the patients, which would have impacts on the degradation behaviors of magnesium alloy implants. In this work, the bio-corrosion behaviors of AZ31B magnesium alloy under alternating cyclic dynamic loads with different low frequencies (0.1-2.5 Hz) were specially investigated. It was found that the bio-degradation performances under external dynamic stressed conditions were much severer than those under unstressed conditions and static loads. The corrosion rates were generally accelerated as the rise of cyclic frequency. Hereby a numerical model for the degradation process of Mg alloy was established. The corrosion current density i corr of Mg alloy and the applied loading frequency f matches a linear relationship of ln i corr ∝ f, which is the result of interactions between the cyclic alternating load and corrosive environment. This work could provide a theoretical reference and an experimental basis for further researches on the biodegradation behaviors of biomedical materials under dynamic conditions.