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.

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.

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.

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.

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.

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.

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.

Black phosphorus-incorporated novel Ti-12Mo-10Zr implant for multimodal treatment of osteosarcoma.

The repair and reconstruction of large bone defects after bone tumor resection is still a great clinical challenge. At present, orthopedic implant reconstruction is the mainstream treatment for repairing bone defects. However, according to clinical feedback, local tumor recurrence and nonunion of bone graft are common reasons leading to the failure of bone defect repair and reconstruction after bone tumor resection, which seriously threaten the physical and mental health of patients. On this basis, here the self-developed low modulus Ti-12Mo-10Zr alloy (TMZ) was chosen as substrate material. To improve its biological activity and osteointegration, calcium, oxygen, and phosphorus co-doped microporous coating was prepared on TMZ alloy by microarc oxidation (MAO). Then, black phosphorus (BP) nanosheets were incorporated onto MAO treated TMZ alloy to obtain multifunctional composites. The obtained BP-MAO-TMZ implant exhibited excellent photothermal effects and effective ablation of osteosarcoma cancer cells under the irradiation of 808 nm near infrared laser, while no photothermal or therapeutic effects were observed for TMZ alloy. Meanwhile, the structure/component bionic coating obtained after MAO treatment as well as the P-driven in situ biomineralization performance after incorporation of BP nanosheets endowed BP-MAO-TMZ implant with synergistic promoting effect on MC3T3-E1 osteoblasts' activity, proliferation and differentiation ability. This study is expected to provide effective clinical solutions for problems of difficult bone regeneration and tumor recurrence after tumor resection in patients with bone tumors and to solve a series of medical problems such as poor prognosis and poor postoperative quality of patients life with malignant bone tumors.

Immunomodulatory effect of Ti-Cu alloy by surface nanostructure synergistic with Cu2+ release.

The inflammatory response induced by implant/macrophage interaction has been considered to be one of the vital factors in determining the success of implantation. In this study, TiCuNxOy coating with an immunomodulatory strategy was proposed for the first time, using nanostructured TiCuNxOy coating synthesized on Ti-Cu alloy by oxygen and nitrogen plasma-based surface modification. It was found that TiCuNxOy coating inhibited macrophage proliferation but stimulated macrophage preferential activation and presented an elongated morphology due to the surface nanostructure. The most encouraging discovery was that TiCuNxOy coating promoted the initial pro-inflammatory response of macrophages and then accelerated the M1-to-M2 transition of macrophages via a synergistic effect of fast-to-slow Cu2+ release and surface nanostructure, which was considered to contribute to initial infection elimination and tissue healing. As expected, TiCuNxOy coating released desirable Cu2+ and generated a favorable immune response that facilitated HUVEC recruitment to the coating, and accelerated proliferation, VEGF secretion and NO production of HUVECs. On the other hand, it is satisfying that TiCuNxOy coating maintained perfect long-term antibacterial activity (≥99.9%), mainly relying on Cu2O/CuO contact sterilization. These results indicated that TiCuNxOy coating might offer novel insights into the creation of a surface with immunomodulatory effects and long-term bactericidal potential for cardiovascular applications.

A Novel PTH-Related Peptide Combined With 3D Printed Macroporous Titanium Alloy Scaffold Enhances Osteoporotic Osseointegration.

Previous parathyroid hormone (PTH)-related peptides (PTHrPs) cannot be used to prevent implant loosening in osteoporosis patients due to the catabolic effect of local sustained release. A novel PTHrP (PTHrP-2) that can be used locally to promote osseointegration of macroporous titanium alloy scaffold (mTAS) and counteract implant slippage in osteoporosis patients is designed. In vitro, PTHrP-2 enhances the proliferation, adhesion, and osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) within the mTAS. Further, it promotes proliferation, migration, angiogenesis-related protein expression, and angiogenesis in human umbilical vein endothelial cells (HUVECs). Compared to PTH(1-34), PTHrP-2 can partially weaken the osteoclast differentiation of RAW 264.7 cells. Even in an oxidative stress microenvironment, PTHrP-2 safeguards the proliferation and migration of BMSCs and HUVECs, reduces reactive oxygen species generation and mitochondrial damage, and partially preserves the angiogenesis of HUVECs. In the Sprague-Dawley (SD) rat osteoporosis model, the therapeutic benefits of PTHrP-2-releasing mTAS (mTASP2 ) and ordinary mTAS implanted for 12 weeks via micro-CT, sequential fluorescent labeling, and histology are compared. The results demonstrate that mTASP2 exhibits high bone growth rate, without osteophyte formation. Consequently, PTHrP-2 exhibits unique local synthesis properties and holds the potential for assisting the osseointegration of alloy implants in osteoporosis patients.

Host-device interactions: exposure of lung epithelial cells and fibroblasts to nickel, titanium, or nitinol affect proliferation, reactive oxygen species production, and cellular signaling.

Endoscopic implantation of medical devices for the treatment of lung diseases, including airway stents, unidirectional valves and coils, is readily used to treat central airway disease and emphysema. However, granulation and fibrotic tissue formation impairs treatment effectiveness. To date little is known about the interaction between implanted devices, often made from metals, such as nickel, titanium or nitinol, and cells in the airways. Here, we study the response of lung epithelial cells and fibroblasts to implant device materials. The adhesion and proliferation of bronchial epithelial cells and lung fibroblasts upon exposure to 10 × 3 × 1 mm pieces of nickel, titanium or nitinol is examined using light and scanning electron microscopy. Pro-inflammatory cytokine mRNA expression and release, signaling kinase activity and intracellular free radical production are assessed. Nitinol, and to a lesser extent nickel and titanium, surfaces support the attachment and growth of lung epithelial cells. Nitinol induces a rapid and significant alteration of kinase activity. Cells directly exposed to nickel or titanium produce free radicals, but those exposed to nitinol do not. The response of lung epithelial cells and fibroblasts depends on the metal type to which they are exposed. Nitinol induces cellular surface growth and the induction of kinase activity, while exposure of lung epithelial cells to nickel and titanium induces free radical production, but nitinol does not.

In Vitro and In Vivo Studies of Antibacterial Coatings on Titanium Alloy Implants for Veterinary Application.

The aim of this work was the evaluation of biological properties of hybrid coatings modified with Ag, Cu, and Zn nanoparticles (NPs) applied on TPLO medical implants by the sol-gel process. The implant coatings enriched with various concentrations of metallic NPs were investigated in the in vitro bactericidal efficacy tests against Gram+ and Gram- bacteria and pathogenic yeast. Next, the designed materials were tested on human osteosarcoma cell lines. The cells adhesion, proliferation, viability, and differentiation were investigated. The cell growth wasevaluated using SEM, and the metallic ion release was measured. The results revealed that the NPs concentration in the hybrid layers decreased with the incubation time. In the last stage, the implants were tested in vivo on six canine patients. Three months after the operation, the radiological evaluation of the performed anastomosis was carried out as well as the histopathological evaluation of tissue regeneration. The strongest bactericidal efficacy was observed for the layers containing AgNPs. Along with an increased concentration of metallic additives, a growing toxic effect was clearly observed. The most pronounced toxic effect was especially evident with the AgNPs concentration exceeding 1 mol %. In all the operated patients, no deviations were found during the follow-up examinations in the postoperative period. The low dose of AgNPs in the hybrid layer facilitated the tissue healing process. It was proven that silver nanoparticles may accelerate the bone healing process. The correct tissue reparation was observed.

Porous surface with fusion peptides embedded in strontium titanate nanotubes elevates osteogenic and antibacterial activity of additively manufactured titanium alloy.

It is still a big challenge in orthopedics to treat infected bone defects properly using medical metals. The use of three-dimensional (3D) scaffold materials that simultaneously mimic the skeletal hierarchy and induce sustainable osteogenic and antibacterial functions are a promising solution with an increasing appeal. In this study, we first designed a bifunctional fusion peptide (HHC36-RGD, HR) by linking antimicrobial peptide (HHC36) and arginine-glycine-aspartate (RGD) peptide via 6-aminohexanoic acid. Then the 3D scaffold was fabricated by additive manufacturing, and the strontium titanate nanotube structure (3D-STN) was constructed on its surface. Finally, the HR was anchored to the 3D-STN with the aid of polydopamine (PDA, P), forming the 3D-STN-P-HR scaffold. The results showed that the scaffold exhibited an ordered 3D porous structure, and that the surface was covered by a dense HHC36-RGD layer. Expectedly, the adsorption of PDA effectively slowed down the release of HR. Moreover, the functionalized scaffold had a significant inhibitory effect on Staphylococcus aureus and Escherichia coli, and its antibacterial rate could reach more than 95%. The results of in vitro cell culture experiments demonstrated that the 3D-STN-P-HR scaffold possessed excellent cytocompatibility and could promote the transcription of osteogenic differentiation-related genes and the expression of related proteins. In conclusion, the functionally modified 3D porous titanium alloy scaffold (3D-STN-P-HR) has a balanced antibacterial and osteogenic function, which bodes well for future potential in the customized functional reconstruction of complex-shaped infected bone defects.

Inhibition of microbial extracellular electron transfer corrosion of marine structural steel with multiple alloy elements.

The microbial corrosion of marine structural steels (09CrCuSb low alloy steel (LAS) and Q235 carbon steel (CS)) in Desulfovibrio vulgaris medium and Pseudomonas aeruginosa medium based on seawater was investigated. In the D. vulgaris medium, the weight loss and maximum pit depth of 09CrCuSb LAS were 0.59 and 0.56 times as much as those of Q235 CS, respectively. Meanwhile, in the P. aeruginosa medium, the values were 0.53 and 0.67 times, respectively. Compared to Q235 CS, 09CrCuSb LAS contains more alloy elements (Cr, Ni, Cu, Al and Sb), which led to obvious inhibition of sessile bacteria growth but had no effect on planktonic bacteria. The number of live sessile cells on the 09CrCuSb LAS surface was 23.4 % and 26.9 % of that on the Q235 CS surface in the D. vulgaris medium and P. aeruginosa medium, respectively. Fewer sessile cells on the steel surface led to a lower extracellular electron transfer (EET) rate so that less corrosion occurred. In addition, the combined effect of alloying elements on grain refinement and passive film formation also improved the anti-corrosion property of the steels.

Endowing biodegradable Zinc implants with dual-function of antibacterial ability and osteogenic activity by micro-addition of Mg and Ag (≤ 0.1 wt.%).

Infection remains the devastating complications associated with surgical fixation of bones fractured during trauma. In this study, we report a low-alloyed Zn-Mg-Ag that simultaneously has optimized strength degeneration profiles during degradation, outstanding antibacterial efficacy and osteogenic activity. Our results showed that Zn-0.05Mg-0.1Ag alloy had favorable mechanical properties (UTS: 247.8 ± 1.6 MPa, Elong.: 35 ± 2.2 %) and presented a better hold of mechanical integrity than pure Zn during 28 days corrosion, 2.6 % vs. 18.7 % reduction. After one-year of natural aging, the alloy still preserved an elongation of 24.07 ± 3.84 %. As verified by microbial cultures, Zn-0.05Mg-0.1Ag alloy demonstrated high antibacterial performance against Gram-positive and Gram-negative strains, as well as antibiotic-resistant strains (MRSA) in vitro and in vivo due to the synergistic antibacterial actions of Zn2+ and Ag+. Meanwhile, Zn-Mg-Ag alloy also exhibited enhanced viability, osteogenic differentiation, and gene expressions of osteoblasts in vitro, as well as promoted osteogenic activity than pure Zn in the femoral condyle defect repair model. The co-releasing of Zn, Mg and Ag ions did not induce toxic side effects. Collectively, low alloyed Zn-0.05Mg-0.1Ag indicated long-lasting mechanical integrity during degradation, and presented the ability to synergistically inhibit bacteria and promote osteogenesis, possessing tremendous potential in treating implant-associated infections. STATEMENT OF SIGNIFICANCE: Infection after fracture fixation (IAFF) remains the most common and serious side effects of orthopedic surgery. Additionally, widespread antibiotic use contributes to the development of multi-drug resistant bacteria such as methicillin-resistant staphylococcus aureus (MRSA), which exacerbates IAFF treatment and prevention. IAFF treatment and prevention remain clinically challenging, so implants with dual antibacterial and osteogenic functions are in high demand. The antibacterial efficacy and osteogenic activity of low-alloyed Zn-Mg-Ag (≤0.1 wt.% Mg, Ag) alloys were investigated in vitro and in vivo. The results showed that micro addition of Mg and Ag could significantly improve osseointegration function, mechanical properties, and antibacterial performance. These quantification findings shed new light on the development and understanding of dual functional Zn-based orthopedic implants.

Calcium-Zinc Phosphate Chemical Conversion Coating Facilitates the Osteointegration of Biodegradable Zinc Alloy Implants by Orchestrating Macrophage Phenotype.

Zinc (Zn) alloys provide a new generation for orthopedic applications due to their essential physiological effects and promising degradation properties. However, excessive release of Zn ions (Zn2+ ) during degradation and the severe inflammatory microenvironment are not conducive to osseointegration, which is determined by the characteristics of the implant surface. Therefore, it is essential to modulate the release rate of Zn alloys by surface modification technology and endow them with anti-inflammatory and osteogenic effects. In this study, two kinds of phosphate chemical conversion (PCC) coatings with different compositions and morphological structures are prepared, namely Zn-P (with disk-like crystals) and Ca-Zn-P (with lamellar crystals). Although all the PCC-coated Zn implants have low cytotoxicity, Ca-Zn-P show better osteoimmunomodulation effects in several aspects: the induction of the M2-phenotype macrophage polarization and thus promotion of osteogenesis in vitro; the regulation of the bone immune microenvironment which is conducive to tissue regeneration and osseointegration in vivo; and the release of ions (through PI3K/AKT and Wnt signaling pathways) and the morphological structures (through RhoGTPase signaling pathways) act as possible mechanisms of M2 polarization. The Ca-Zn-P coating can be considered to provide new insights into bone immunomodulation and osseointegration.

Complementary and Synergistic Design of Bi-Layered Double Hydroxides Modified Magnesium Alloy toward Multifunctional Orthopedic Implants.

Magnesium (Mg)-based alloys have been regarded as promising implants for future clinic orthopedics, however, how to endow them with good anti-corrosion and biofunctions still remains a great challenge, especially for complicated bone diseases. Herein, three transition metals (M = Mn, Fe, and Co)-containing layered double hydroxides (LDH) (LDH-Mn, LDH-Fe, and LDH-Co) with similar M content are prepared on Mg alloy via a novel two-step method, then systematic characterizations and comparisons are conducted in detail. Results showed that LDH-Mn exhibited the best corrosion resistance, LDH-Mn and LDH-Co possessed excellent photothermal and enzymatic activities, LDH-Fe revealed better cytocompatibility and antibacterial properties, while LDH-Co demonstrated high cytotoxicity. Based on these results, an optimized bilayer LDH coating enriched with Fe and Mn (LDH-MnFe) from top to bottom have been designed for further in vitro and in vivo analysis. The top Fe-riched layer provided biocompatibility and antibacterial properties, while the bottom Mn-riced layer provided excellent anti-corrosion, photothermal and enzymatic effects. In addition, the released Mg, Fe, and Mn ions have a positive influence on angiogenesis and osteogenesis. Thus, the LDH-MnFe showed complementary and synergistic effects on anti-corrosion and multibiofunctions (antibacteria, antitumor, and osteogenesis). The present work offers a novel multifunctional Mg-based implant for treating bone diseases.

Morphofunctional reaction of leukocytes and platelets in in vitro contact with a-C:H:SiOx -coated Ti-6Al-4V substrate.

The article deals with the plasma-assisted chemical vapor deposition of 0.3-1.4 µm thick a-C:H:SiOx films in a mixture of argon and polyphenylmethylsiloxane vapor onto the Ti-6Al-4V alloy substrate, which is often used as an implant material. The a-C:H:SiOx film structure is studied by the Fourier-transform infrared and Raman spectroscopies. The pull-off adhesion test assesses the adhesive strength of a-C:H:SiOx films, and the ball-on-disk method is employed to measure their wear rate and friction coefficient. According to these studies, a-C:H:SiOx films are highly adhesive to the Ti-6Al-4V substrate, have low (0.056) friction coefficient and wear rate (9.8 × 10-8  mm3  N-1  m-1 ) in phosphate-buffered saline at 40°C. In vitro studies show neither thrombogenicity nor cytotoxicity of the a-C:H:SiOx film for the human blood mononuclear cells (hBMNCs). The in vitro contact between the hBMNC culture and a-C:H:SiOx films 0.8-1.4 µm thick deposited onto Ti-6Al-4V substrates reduces a 24-hour secretion of pro-inflammatory cytokines and chemokines IL-8, IL-17, TNFα, RANTES, and MCP-1. This reduction is more significant when the film thickness is 1.4 µm and implies its potential anti-inflammatory effect and possible application in cardiovascular surgery. The dependence is suggested for the concentration of anti-inflammatory cytokines and chemokines and the a-C:H:SiOx film thickness, which correlates with the surface wettability and electrostatic potential. The article discusses the possible applications of the anti-inflammatory effect and low thrombogenicity of a-C:H:SiOx films in cardiovascular surgery.

Magnesium Alloys in Orthopedics: A Systematic Review on Approaches, Coatings and Strategies to Improve Biocompatibility, Osteogenic Properties and Osteointegration Capabilities.

There is increasing interest in using magnesium (Mg) alloy orthopedic devices because of their mechanical properties and bioresorption potential. Concerns related to their rapid degradation have been issued by developing biodegradable micro- and nanostructured coatings to enhance corrosion resistance and limit the release of hydrogen during degradation. This systematic review based on four databases (PubMed®, Embase, Web of Science™ and ScienceDirect®) aims to present state-of-the-art strategies, approaches and materials used to address the critical factors currently impeding the utilization of Mg alloy devices. Forty studies were selected according to PRISMA guidelines and specific PECO criteria. Risk of bias assessment was conducted using OHAT and SYRCLE tools for in vitro and in vivo studies, respectively. Despite limitations associated with identified bias, the review provides a comprehensive analysis of preclinical in vitro and in vivo studies focused on manufacturing and application of Mg alloys in orthopedics. This attests to the continuous evolution of research related to Mg alloy modifications (e.g., AZ91, LAE442 and WE43) and micro- and nanocoatings (e.g., MAO and MgF2), which are developed to improve the degradation rate required for long-term mechanical resistance to loading and excellent osseointegration with bone tissue, thereby promoting functional bone regeneration. Further research is required to deeply verify the safety and efficacy of Mg alloys.

Aspirin/PLGA coated 3D-printed Ti-6Al-4V alloy modulate macrophage polarization to enhance osteoblast differentiation and osseointegration.

Although titanium (Ti) and Ti-based alloy have been widely used as dental and orthopedic implant materials, its bioinertness hindered the rapid osseointegration. Therefore, it is recommended to acquire ideal topographic and chemical characteristics through surface modification methods. 3D printing is a delicate manufacture technique which possesses superior controllability and reproducibility. While aspirin serve as a well-established non-steroidal anti-inflammatory agent. Recently, the importance of immune system in regulating bone dynamics has attracted increasing attention. We herein superimposed the aspirin/poly (lactic-co-glycolic acid) (ASP/PLGA) coating on the 3D-printed Ti-6Al-4V surface with uniform micro-structure to establish the Ti64-M-ASP/PLGA substrate. Scanning electron microscopy (SEM), x-ray photoelectron spectroscopy (XPS) and contact angle test confirmed the successful fabrication of the Ti64-M-ASP/PLGA substrate, with increased wettability and sustained release pattern of ASP. Compared with the Ti64 base material, the Ti64-M-ASP/PLGA substrate showed enhanced M2 and depressed M1 genes and proteins expressions in macrophages. The novel Ti64-M-ASP/PLGA substrate also displayed enhanced osteoblast proliferation, adhesion, extracellular mineralization ability and osteogenic gene expressions when cultured with macrophage conditioned medium in vitro. Furthermore, rat femora implantation model was used for in vivo evaluation. After 4 weeks of implantation, push out test, micro-computed tomography (micro-CT) and histological analyses all confirmed the superior osseointegration capabilities of the Ti64-M-ASP/PLGA implant than the other groups. Our study revealed the synergistic role played by 3D-printed micro topography and immunoregulatory drug aspirin in promoting osteogenesis in vitro and accelerating osseointegration in vivo, thus providing a promising method for better modifying the implant surface. Graphical abstract.