In vitro corrosion and cytocompatibility of Mg-Zn-Ca alloys coated with FHA.

In the field of orthopedics, it's crucial to effectively slow down the degradation rate of Mg alloys. This study aims to improve the degradation behavior of Mg-Zn-Ca alloys by electrodepositing fluorohydroxyapatite (FHA). We investigated the microstructure and bond strength of the deposition, as well as degradation and cellular reactions. After 15-30 days of degradation in Hanks solution, FHA deposited alloys showed enhanced stability and less pH change. The strong interfacial bond between FHA and the Mg-Zn-Ca substrate was verified through scratch tests (Critical loads: 10.73 ± 0.014 N in Mg-Zn-0.5Ca alloys). Cellular studies demonstrated that FHA-coated alloys exhibited good cytocompatibility and promoted the growth of MC3T3-E1 cells. Further tests showed FHA-coated alloys owed improved early bone mineralization and osteogenic properties, especially in Mg-Zn-0.5Ca. This research highlighted the potential of FHA-coated Mg-Zn-0.5Ca alloys in orthopedics applications.

Coatless modification of 3D-printed Ti6Al4V implants through tailored Cu ion implantation combined with UV photofunctionalization to enhance cell attachment, osteogenesis and angiogenesis.

The three-dimensional-printed Ti6Al4V implant (3DTi) has been widely accepted for the reconstruction of massive bone defects in orthopedics owing to several advantages, such as its tailored shape design, avoiding bone graft and superior bone-implant interlock. However, the osteoinduction activity of 3DTi is inadequate when applied clinically even though it exhibits osteoconduction. This study developes a comprehensive coatless strategy for the surface improvement of 3DTi through copper (Cu) ion implantation and ultraviolet (UV) photofunctionalization to enhance osteoinductivity. The newly constructed functional 3DTi (UV/Ti-Cu) achieved stable and controllable Cu doping, sustained Cu2+ releasing, and increased surface hydrophilicity. By performing cellular experiments, we determined that the safe dose range of Cu ion implantation was less than 5×1016 ions/cm2. The implanted Cu2+ enhanced the ALP activity and the apatite formation ability of bone marrow stromal cells (BMSCs) while slightly decreasing proliferation ability. When combined with UV photofunctionalization, cell adhesion and proliferation were significantly promoted and bone mineralization was further increased. Meanwhile, UV/Ti-Cu was conducive to the migration and angiogenesis of human umbilical vein endothelial cells (HUVECs) in vitro, theoretically facilitating vascular coupling osteogenesis. In conclusion, UV/Ti-Cu is a novel attempt to apply two coatless techniques for the surface modification of 3DTi. In addition, it is considered a potential bone substrate for repairing bone defects.

Rhodium-Rhenium Alloy Nanozymes for Non-inflammatory Photothermal Therapy.

Analogous to thermal ablation techniques in clinical settings, cell necrosis induced during tumor photothermal therapy (PTT) can provoke an inflammatory response that is detrimental to the treatment of tumors. In this study, we employed a straightforward one-step liquid-phase reduction process to synthesize uniform RhRe nanozymes with an average hydrodynamic size of 41.7 nm for non-inflammatory photothermal therapy. The obtained RhRe nanozymes showed efficient near-infrared (NIR) light absorption for effective PTT, coupled with a remarkable capability to scavenge reactive oxygen species (ROS) for anti-inflammatory treatment. After laser irradiation, the 4T1 tumors were effectively ablated without obvious tumor recurrence within 14 days, along with no obvious increase in pro-inflammatory cytokine levels. Notably, these RhRe nanozymes demonstrated high biocompatibility with normal cells and tissues, both in vitro and in vivo, as evidenced by the lack of significant toxicity in female BALB/c mice treated with 10 mg/kg of RhRe nanozymes over a 14 day period. This research highlights RhRe alloy nanoparticles as bioactive nanozymes for non-inflammatory PTT in tumor therapy.

Laser-assisted surface alloying of titanium with silver to enhance antibacterial and bone-cell mineralization properties of orthopedic implants.

Orthopedic device-related infection (ODRI) poses a significant threat to patients with titanium-based implants. The challenge lies in developing antibacterial surfaces that preserve the bulk mechanical properties of titanium implants while exhibiting characteristics similar to bone tissue. In response, we present a two-step approach: silver nanoparticle (AgNP) coating followed by selective laser-assisted surface alloying on commonly used titanium alumina vanadium (TiAl6V4) implant surfaces. This process imparts antibacterial properties without compromising the bulk mechanical characteristics of the titanium alloy. Systematic optimization of laser beam power (8-40 W) resulted in an optimized surface (32 W) with uniform TiAg alloy formation. This surface displayed a distinctive hierarchical mesoporous textured surface, featuring cauliflower-like nanostructures measuring between 5-10 nm uniformly covering spatial line periods of 25 µm while demonstrating homogenous elemental distribution of silver throughout the laser processed surface. The optimized laser processed surface exhibited prolonged superhydrophilicity (40 days) and antibacterial efficacy (12 days) against Staphylococcus aureus and Escherichia coli. Additionally, there was a significant twofold increase in bone mineralization compared to the pristine Ti6Al4V surface (p < 0.05). Rockwell hardness tests confirmed minimal (<1%) change in bulk mechanical properties compared to the pristine surface. This innovative laser-assisted approach, with its precisely tailored surface morphology, holds promise for providing enduring antibacterial and osteointegration properties, rendering it an optimal choice for modifying load-bearing implant devices without altering material bulk characteristics.

Biomimicking covalent organic frameworks nanocomposite coating for integrated enhanced anticorrosion and antifouling properties of a biodegradable magnesium stent.

The utilization of biodegradable magnesium (Mg) alloys in the fabrication of temporary non-vascular stents is an innovative trend in biomedical engineering. However, the heterogeneous degradation profiles of these biomaterials, together with potential bacterial colonization that could precipitate infectious or stenotic complications, are critical obstacles precluding their widespread clinical application. In pursuit of overcoming these limitations, this study applies the principles of biomimicry, particularly the hydrophobic and anti-fouling characteristics of lotus leaves, to pioneer the creation of nanocomposite coatings. These coatings integrate poly-trimethylene carbonate (PTMC) with covalent organic frameworks (COFs), to modify the stent's surface property. The strategic design of the coating's topography, porosity, and self-polishing capabilities collectively aims to decelerate degradation processes and minimize biological adhesion. The protective qualities of the coatings were substantiated through rigorous testing in both in vitro dynamic bile tests and in vivo New Zealand rabbit choledochal models. Empirical findings from these trials confirmed that the implementation of COF-based nanocomposite coatings robustly fortifies Mg implantations, conferring heightened resistance to both biocorrosion and biofouling as well as improved biocompatibility within bodily environments. The outcomes of this research elucidate a comprehensive framework for the multifaceted strategies against stent corrosion and fouling, thereby charting a visionary pathway toward the systematic conception of a new class of reliable COF-derived surface modifications poised to amplify the efficacy of Mg-based stents. STATEMENT OF SIGNIFICANCE: Biodegradable magnesium (Mg) alloys are widely utilized in temporary stents, though their rapid degradation and susceptibility to bacterial infection pose significant challenges. Our research has developed a nanocomposite coating inspired by the lotus, integrating poly-trimethylene carbonate with covalent organic frameworks (COF). The coating achieved self-polishing property and optimal surface energy on the Mg substrate, which decelerates stent degradation and reduces biofilm formation. Comprehensive evaluations utilizing dynamic bile simulations and implantation in New Zealand rabbit choledochal models reveal that the coating improves the durability and longevity of the stent. The implications of these findings suggest the potential COF-based Mg alloy stent surface treatments and a leap forward in advancing stent performance and endurance in clinical applications.

Biocompatibility and Osseointegration of the Biomimetically Coated and Water-Soluble Eggshell Membrane Protein Cross-Linked Ti Alloy Screws.

Background: The surface properties of dental and orthopedic implants are directly related to their osseointegration rate. Coating and/or modifying the implant surface might reduce the time of healing. In this study, we aimed to examine the effects of a hybrid surface consisting of a brushite surface coating and cross-linked water-soluble eggshell membrane protein on the osseointegration of titanium (Ti) screws under in vivo conditions. Methods: Twenty Ti alloy screws were implanted monocortically in anteromedial regions of New Zealand rabbit tibiae. Ten screws were untreated and used as controls. The remaining 10 screws were coated with calcium phosphate and following cross-linked with ostrich eggshell membrane protein. All rabbits were sacrificed six weeks after the surgery. Peri-screw tissues were evaluated by micro-computed tomography (µ-CT), histological and histomorphometrical methods. Results: The µ-CT assessments indicated that the experimental group had significantly higher mean bone surface area (BSA) and trabeculae number (TbN) than those of the control group (p ˂ 0.05). Bone surface area (BV), trabecular separation (TbSp), trabecular thickness (TbTh), and bone mineral density (BMD) scores of the control and experimental groups were quite similar (p > 0.05). The vascularization score of the experimental group was significantly higher than the control group (4.29 vs. 0.92%). No sign of the graft-versus-host reaction was observed. Conclusion: Our findings reveal that coating Ti alloy implants with calcium phosphate cross-linked with ostrich eggshell membrane protein increases the osseointegration of Ti alloy screws by increasing the bone surface area, number of trabeculae and vascularization in the implant site.

Heterogeneous nucleation induced A. pernyi/B. mori silk fibroin coatings on AZ31 biometals with enhanced corrosion resistance, adhesion and biocompatibility.

Silk fibroin coatings on biomedical magnesium alloys have garnered significant attention due to their enhanced corrosion resistance and biocompatibility. However, the utilization of wild A. pernyi silk fibroin, known for its RGD sequence that facilitates tissue regeneration, presents a challenge for corrosion-resistant coatings on magnesium alloys due to its weak adhesion and high dissolution rate. In this study, we employed hexafluoroisopropanol as a solvent to blend A. pernyi silk fibroin with B. mori silk fibroin. The resulting blended fibroin coating at a 3:7 mass ratio exhibited a heterogeneous nucleation effect, enhancing ß-sheet content (32.3 %) and crystallinity (28.6 %). This improved ß-sheet promoted the "labyrinth effect" with an Icorr of 2.15 × 10-6 A cm-2, resulting in significantly improved corrosion resistance, which is two orders of magnitude lower than that of pure magnesium alloy. Meanwhile, the increased content of exposed serine in zigzag ß-sheet contributes to a higher adhesion strength. Cell cytotoxicity evaluation confirmed the enhanced cell adhesion and bioactivity. This work provides a facile approach for wild A. pernyi silk fibroin coatings on magnesium alloys with enhanced corrosion resistance, adhesion and biocompatibility.

Functionalized chitosan hydrogel promotes osseointegration at the interface of3D printed titanium alloy scaffolds.

Autogenous bone transplantation is a prevalent clinical method for addressing bone defects. However, the limited availability of donor bone and the morbidity associated with bone harvesting have propelled the search for suitable bone substitutes. Bio-inspired scaffolds, particularly those fabricated using electron beam melting (EBM) deposition technology, have emerged as a significant advancement in this field. These 3D-printed titanium alloy scaffolds are celebrated for their outstanding biocompatibility and favorable elastic modulus. Thermosensitive chitosan hydrogel, which transitions from liquid to solid at body temperature, serves as a popular carrier in bone tissue engineering. Icariin (ICA), known for its efficacy in promoting osteoblast differentiation from bone marrow mesenchymal stem cells (BMSCs), plays a crucial role in this context. We developed a system combining a 3D-printed titanium alloy with a thermosensitive chitosan hydrogel, capable of local bone regeneration and integration through ICA delivery. Our in vitro findings reveal that this system can gradually release ICA, demonstrating excellent biocompatibility while fostering BMSC proliferation and osteogenic differentiation. Immunohistochemistry and Micro-CT analyses further confirm the effectiveness of the system in accelerating in vivo bone regeneration and enhancing osseointegration. This composite system lays a significant theoretical foundation for advancing local bone regeneration and integration.

Functionalized magnesium alloys obtained by superplastic forming process retain osteoinductive and antibacterial properties: An in-vitro study.

OBJECTIVES: This study aimed to investigate the biocompatibility, osteogenic and antibacterial activity of biomedical devices based on Magnesium (Mg) Alloys manufactured by Superplastic Forming process (SPF) and subjected to Hydrothermal (HT) and Sol-Gel Treatment (Sol-Gel). METHODS: Mg-SPF devices subjected to Hydrothermal (Mg-SPF+HT) and Sol-Gel Treatment (Mg-SPF+Sol-Gel) were investigated. The biocompatibility of Mg-SPF+Sol-Gel and Mg-SPF+HT devices was observed by indirect and direct cytotoxicity assays, whereas the colonization of sample surfaces was assessed by confocal microscopy. qRT-PCR analysis and microbial growth curve analyses were employed to evaluate the osteogenic and antibacterial activity of both SPF-Mg treated devices, respectively. RESULTS: Mg-SPF+HT and Mg-SPF+Sol-Gel showed a high degree of biocompatibility. Analysis of mRNA expression of osteogenic genes in cells cultured on Mg-treated devices revealed a significant upregulation of the expression levels of BMP2 and Runx-2. Furthermore, the bacterial growth in strains developed in contact with both the Mg-SPF+HT and Mg-SPF+Sol-Gel devices was lower than that observed in the control. SIGNIFICANCE: Hydrothermal and Sol-Gel Treatments of Mg alloys obtained through the SPF process demonstrated bioactive, osteogenic and antibacterial activity, offering a promising alternative to conventional Mg-based devices. The obtained Mg-based materials may have the potential to enhance the tunability of temporary devices in maxillary reconstruction, eliminating the need for second surgeries, and ensuring a good bone reconstruction and a reduced implant failure rate due to bacterial infections.

A Cu(â ¡)-eluting coating through silk fibroin film on ZE21B alloy designed for in situ endotheliazation biofunction.

In the cardiovascular field, coating containing copper used to catalyze NO (nitric oxide) production on non-degradable metal surfaces have shown unparalleled expected performance, but there are few studies on biodegradable metal surfaces. Magnesium-based biodegradable metals have been applied in cardiovascular field in large-scale because of their excellent properties. In this study, the coating of copper loaded in silk fibroin is fabricated on biodegradable ZE21B alloy. Importantly, the different content of copper is set to investigate the effects of on the degradation performance and cell behavior of magnesium alloy. Through electrochemical and immersion experiments, it is found that high content of copper will accelerate the corrosion of magnesium alloy. The reason is the spontaneous micro-batteries between copper and magnesium with the different standard electrode potentials, that is, the galvanic corrosion accelerates the corrosion of magnesium alloy. Moreover, the coating formed through silk fibroin by the right amount copper not only have a protective effect on the ZE21B alloy substrate, but also promotes the adhesion and proliferation of endothelial cells in blood vessel micro-environment. The production of NO catalyzed by copper ions makes this trend more significant, and inhibits the excessive proliferation of smooth muscle cells. These findings can provide guidance for the amount of copper in the coating on the surface of biodegradable magnesium alloy used for cardiovascular stent purpose.

Magnesium-lithium thin films for neurological applications-An in vitro investigation of glial cytocompatibility and neuroinflammatory response.

Lithium (Li), a widely used drug for bipolar disorder management, is associated with many side effects due to systemic exposure. The localized delivery of lithium through implants could be an approach to overcome this challenge, for which biodegradable magnesium (Mg)-based materials are a promising choice. In this study, we focus on Mg-Li thin film alloys as potential Li-releasing implants. Therefore, we investigated the in vitro short-term corrosion behavior and cytocompatibility of two alloys, Mg-1.6wt%Li and Mg-9.5wt%Li. As glial cells are the key players of foreign body responses to implants, we used human glial cell lines for cytocompatibility studies, and a murine brain slice model for a more holistic view at the neuroinflammatory response. We found that Mg-1.6wt%Li corrodes approximately six times slower than Mg-9.5wt%Li. Microscopic analysis showed that the material surface (Mg-1.6wt%Li) is suitable for cell adhesion. The cytocompatibility test with Mg-1.6wt%Li and Mg-9.5wt%Li alloy extracts revealed that both cell types proliferated well up to 10 mM Mg concentration, irrespective of the Li concentration. In the murine brain slice model, Mg-1.6wt%Li and Mg-9.5wt%Li alloy extracts did not provoke a significant upregulation of glial inflammatory/ reactivity markers (IL-1ß, IL-6, FN1, TNC) after 24 h of exposure. Furthermore, the gene expression of IL-1ß (up to 3-fold) and IL-6 (up to 16-fold) were significantly downregulated after 96 h, and IL-6 downregulation showed a Li concentration dependency. Together, these results indicate the acute cytocompatibility of two Mg-Li thin film alloys and provide basis for future studies to explore promising applications of the material. STATEMENT OF SIGNIFICANCE: We propose the idea of lithium delivery to the brain via biodegradable implants to reduce systemic side effects of lithium for bipolar disorder therapy and other neurological applications. This is the first in vitro study investigating Mg-xLi thin film degradation under physiological conditions and its influence on cellular responses such as proliferation, viability, morphology and inflammation. Utilizing human brain-derived cell lines, we showed that the material surface of such a thin film alloy is suitable for normal cell attachment. Using murine brain slices, which comprise a multicellular network, we demonstrated that the material extracts did not elicit a pro-inflammatory response. These results substantiate that degradable Mg-Li materials are biocompatible and support the further investigation of their potential as neurological implants.

Bimetallic Gold/Silver and Bioactive Camptothecin Hybrid Nanoparticles for Eradication of Cancer Stem Cells in a Combination Manner.

The defeat of cancer is still a challenge due to the existence of cancer stem cells (CSCs) because they resist conventional chemotherapy via multifactor regulated mechanisms. Consequently, one-dimensional action toward CSCs cannot work. Herein, we used rationally designed hybrid nanoparticles as a combined cancer therapy, hoping to form a multidimensional control network. In this paper, gold/silver alloy nanoparticle decorated camptothecin nanocrystals were formulated according to complementary anti-CSC mechanisms from gold, silver, and organic drug. This smart drug formulation could combine chemotherapy and thermotherapy, target different tumor sites, and demonstrate versatile toxicity profiles from each component. Major results indicated that this nanosystem demonstrated indiscriminately effective cytotoxic/proapoptotic/necrotic activity against bulk MCF-7 cells and their CSC subpopulation, in particular under laser ablation. Moreover, this nanosystem displayed enhanced antineoplastic activity against CSC spheroids, resulting in a significant reduction in their number and size, that is, their self-renewal capacity. All the results indicated that CSCs upon treatment of these new hybrid nanoparticles underwent reduced stemness and conversion from the original quiescent state and recovered their sensitivity toward chemotherapy. The relevant anticancer mechanism was ascribed to NIR-pH dual responsive drug release, synergistic/combined thermo-chemotherapy of organic drug and inorganic alloy nanoparticles, enhanced cellular uptake mediated by alloy nanoparticles, and Ag+-induced biomembrane damage. This thermo-chemotherapy platform provides a new combinatorial strategy for inorganic and organic agents in the complete elimination of CSCs.

Degradation protection and enhanced biocompatibility of Mg alloys pretreated with plasma proteins.

After implantation of the Mg alloy in the human body, the adsorption of plasma protein on surface will cause a series of cell reactions and affect the degradation of Mg alloys. Herein, in vitro biological reactions of the ZK60 and AZ31 Mg alloys are analyzed in plasma protein environment. Combined with mass spectrometry analysis of the type of adsorbed proteins, it is shown that proteins such as fibrinogen, vitronectin, fibronectin, and prothrombin are prone to get adsorbed on the surface of the alloys than other proteins, leading to the promotion of MG63 cell adhesion and proliferation. The effect of selected proteins (fibrinogen, fibronectin, and prothrombin) on degradation of ZK60 and AZ31 Mg alloys is investigated using immersion tests. The degradation of AZ31 Mg alloy is significantly restrained with the presence of proteins. This is due to the protein adsorption effect on the sample surface. The molecular dynamics simulation results indicate that both fibrinogen and fibronectin tend to adsorb onto the AZ31 rather than ZK60, forming a stable protein layer on the AZ31 Mg alloy retarding the degradation of the samples. As to ZK60 alloy, the addition of protein inhibits the degradation in the short term, however, the degradation increases after a long time of immersion. This phenomenon is particularly pronounced in fibronectin solution.

A biodegradable Zn-5Gd alloy with biomechanical compatibility, cytocompatibility, antibacterial ability, and in vitro and in vivo osteogenesis for orthopedic applications.

Zinc (Zn) and some of its alloys are recognized as promising biodegradable implant materials due to their acceptable biocompatibility, facile processability, and moderate degradation rate. Nevertheless, the limited mechanical properties and stability of as-cast Zn alloys hinder their clinical application. In this work, hot-rolled (HR) and hot-extruded (HE) Zn-5 wt.% gadolinium (Zn-5Gd) samples were prepared by casting and respectively combining with hot rolling and hot extrusion for bone-implant applications. Their microstructure evolution, mechanical properties, corrosion behavior, cytotoxicity, antibacterial ability, and in vitro and in vivo osteogenesis were systematically evaluated. The HR and HE Zn-5Gd exhibited significantly improved mechanical properties compared with those of their pure Zn counterparts and the HR Zn-5Gd showed a unique combination of tensile properties with an ultimate tensile strength of ∼311.6 MPa, yield strength of ∼236.5 MPa, and elongation of ∼40.6%, all of which are greater than the mechanical properties required for bone-implant materials. The HR and HE Zn-5Gd showed higher corrosion resistance than their pure Zn counterpart in Hanks' solution and the HE Zn-5Gd had the lowest corrosion rate of 155 µm/y measured by electrochemical corrosion and degradation rate of 26.9 µm/y measured by immersion testing. The HR and HE Zn-5Gd showed high cytocompatibility toward MC3T3-E1 and MG-63 cells, high antibacterial effects against S. aureus, and better in vitro osteogenic activity than their pure Zn counterparts. Furthermore, the HE Zn-5Gd exhibited better in vivo biocompatibility, osteogenesis, and osteointegration ability than pure Zn and pure Ti. STATEMENT OF SIGNIFICANCE: This work reports the mechanical properties, corrosion behaviors, cytocompatibility, antibacterial ability, in vitro and in vivo osteogenesis of biodegradable Zn-Gd alloy for bone-implant applications. Our findings demonstrate that the hot-rolled (HR) Zn-5Gd showed a unique combination of tensile properties with an ultimate tensile strength of ∼311.6 MPa, yield strength of ∼236.5 MPa, and elongation of ∼40.6%. The HR and HE Zn-5Gd showed higher corrosion resistance than their pure Zn counterpart in Hanks' solution. The HR and HE Zn-5Gd showed high cytocompatibility toward MC3T3-E1 and MG-63 cells, good antibacterial effects against S. aureus, and better in vitro osteogenic activity. Furthermore, the HE Zn-5Gd exhibited better in vivo biocompatibility, osteogenesis, and osteointegration ability than pure Zn and pure Ti.

Biodegradable Zn-5Dy Alloy with Enhanced Osteo/Angio-Genic Activity and Osteointegration Effect via Regulation of SIRT4-Dependent Mitochondrial Function.

Zinc (Zn)-dysprosium (Dy) binary alloys are promising biodegradable bone fracture fixation implants owing to their attractive biodegradability and mechanical properties. However, their clinical application is a challenge for bone fracture healing, due to the lack of Zn-Dy alloys with tailored proper bio-mechanical and osteointegration properties for bone regeneration. A Zn-5Dy alloy with high strength and ductility and a degradation rate aligned with the bone remodeling cycle is developed. Here, mechanical stability is further confirmed, proving that Zn-5Dy alloy can resist aging in the degradation process, thus meeting the mechanical requirements of fracture fixation. In vitro cellular experiments reveal that the Zn-5Dy alloy enhances osteogenesis and angiogenesis by elevating SIRT4-mediated mitochondrial function. In vivo Micro-CT, SEM-EDS, and immunohistochemistry analyses further indicate good biosafety, suitable biodegradation rate, and great osteointegration of Zn-5Dy alloy during bone healing, which also depends on the upregulation of SIRT4-mediated mitochondrial events. Overall, the study is the first to report a Zn-5Dy alloy that exerts remarkable osteointegration properties and has a strong potential to promote bone healing. Furthermore, the results highlight the importance of mitochondrial modulation and shall guide the future development of mitochondria-targeting materials in enhancing bone fracture healing.

Ultrathin TiO2 Coatings via Atomic Layer Deposition Strongly Improve Cellular Interactions on Planar and Nanotubular Biomedical Ti Substrates.

This work aims to investigate the chemical and/or structural modification of Ti and Ti-6Al-4V (TiAlV) alloy surfaces to possess even more favorable properties toward cell growth. These modifications were achieved by (i) growing TiO2 nanotube layers on these substrates by anodization, (ii) surface coating by ultrathin TiO2 atomic layer deposition (ALD), or (iii) by the combination of both. In particular, an ultrathin TiO2 coating, achieved by 1 cycle of TiO2 ALD, was intended to shade the impurities of F- and V-based species in tested materials while preserving the original structure and morphology. The cell growth on TiO2-coated and uncoated TiO2 nanotube layers, Ti foils, and TiAlV alloy foils were compared after incubation for up to 72 h. For evaluation of the biocompatibility of tested materials, cell lines of different tissue origin, including predominantly MG-63 osteoblastic cells, were used. For all tested nanomaterials, adding an ultrathin TiO2 coating improved the growth of MG-63 cells and other cell lines compared with the non-TiO2-coated counterparts. Here, the presented approach of ultrathin TiO2 coating could be used potentially for improving implants, especially in terms of shading problematic F- and V-based species in TiO2 nanotube layers.

Enhanced Mechanical Properties, Corrosion Resistance, Cytocompatibility, Osteogenesis, and Antibacterial Performance of Biodegradable Mg-2Zn-0.5Ca-0.5Sr/Zr Alloys for Bone-Implant Application.

Magnesium (Mg) alloys are widely used in bone fixation and bone repair as biodegradable bone-implant materials. However, their clinical application is limited due to their fast corrosion rate and poor mechanical stability. Here, the development of Mg-2Zn-0.5Ca-0.5Sr (MZCS) and Mg-2Zn-0.5Ca-0.5Zr (MZCZ) alloys with improved mechanical properties, corrosion resistance, cytocompatibility, osteogenesis performance, and antibacterial capability is reported. The hot-extruded (HE) MZCZ sample exhibits the highest ultimate tensile strength of 255.8 ± 2.4 MPa and the highest yield strength of 208.4 ± 2.8 MPa and an elongation of 15.7 ± 0.5%. The HE MZCS sample shows the highest corrosion resistance, with the lowest corrosion current density of 0.2 ± 0.1 µA cm-2 and the lowest corrosion rate of 4 ± 2 µm per year obtained from electrochemical testing, and a degradation rate of 368 µm per year and hydrogen evolution rate of 0.83 ± 0.03 mL cm-2 per day obtained from immersion testing. The MZCZ sample shows the highest cell viability in relation to MC3T3-E1 cells among all alloy extracts, indicating good cytocompatibility except at 25% concentration. Furthermore, the MZCZ alloy shows good antibacterial capability against Staphylococcus aureus.

Synergistic Amelioration of Osseointegration and Osteoimmunomodulation with a Microarc Oxidation-Treated Three-Dimensionally Printed Ti-24Nb-4Zr-8Sn Scaffold via Surface Activity and Low Elastic Modulus.

Biomaterial scaffolds, including bone substitutes, have evolved from being primarily a biologically passive structural element to one in which material properties such as surface topography and chemistry actively direct bone regeneration by influencing stem cells and the immune microenvironment. Ti-6Al-4V(Ti6Al4V) implants, with a significantly higher elastic modulus than human bone, may lead to stress shielding, necessitating improved stability at the bone-titanium alloy implant interface. Ti-24Nb-4Zr-8Sn (Ti2448), a low elastic modulus ß-type titanium alloy devoid of potentially toxic elements, was utilized in this study. We employed 3D printing technology to fabricate a porous scaffold structure to further decrease the structural stiffness of the implant to approximate that of cancellous bone. Microarc oxidation (MAO) surface modification technology is then employed to create a microporous structure and a hydrophilic oxide ceramic layer on the surface and interior of the scaffold. In vitro studies demonstrated that MAO treatment enhances the proliferation, adhesion, and osteogenesis capabilities on the scaffold surface. The chemical composition of the MAO-Ti2448 oxide layer is found to enhance the transcription and expression of osteogenic genes in bone mesenchymal stem cells (BMSCs), potentially related to the enrichment of Nb2O5 and SnO2 in the oxide layer. The MAO-Ti2448 scaffold, with its synergistic surface activity and low stiffness, significantly activates the anti-inflammatory macrophage phenotype, creating an immune microenvironment that promotes the osteogenic differentiation of BMSCs. In vivo experiments in a rabbit model demonstrated a significant improvement in the quantity and quality of the newly formed bone trabeculae within the scaffold under the contact osteogenesis pattern with a matched elastic modulus. These trabeculae exhibit robust connections to the external structure of the scaffold, accelerating the formation of an interlocking structure between the bone and implant and providing higher implantation stability. These findings suggest that the MAO-Ti2448 scaffold has significant potential as a bone defect repair material by regulating osteoimmunomodulation and osteogenesis to enhance osseointegration. This study demonstrates an optional strategy that combines the mechanism of reducing the elastic modulus with surface modification treatment, thereby extending the application scope of ß-type titanium alloy.

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.

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.