Enhanced Adsorption Stability and Biofunction Durability with Phosphonate-Grafted, PEGylated Copolymer on Hydroxyapatite Surface.

Nonfouling surfaces are crucial in applications such as biosensors, medical implants, marine coatings, and drug delivery vehicles. However, their long-term coating stability and robust surface binding strength in physiological media remain challenging. Herein, a phosphonate-grafted, PEGylated copolymer on the hydroxyapatite (HA) surface is proposed to significantly improve the adsorption stability and thus enhance the biofunction durability accordingly. The phosphoryl (-PO3) grafted branch is employed in the functional polymer to facilitate attaching to the HA substrate. In addition, the polymer integrates the nonfouling polymer brushes of poly(ethylene glycol) (PEG) with the cell-adhesive moiety of cyclic Arg-Gly-Asp-d-Phe-Cys peptides (cRGD). A systematic study on the as-synthesized PEGylated graft copolymer indicates a synergistic binding mechanism of the NH2 and PO3 groups to HA, achieving a high surface coverage with desirable adsorption stability. The cRGD/PEGylated copolymers of optimized grafting architecture are proven to effectively adsorb to HA surfaces as a self-assembled copolymer monolayer, showing stability with minimal desorption even in a complex, physiological medium and effectively preventing nonspecific protein adsorption as examined with X-ray photoelectron spectroscopy (XPS) and a quartz crystal microbalance with dissipation (QCM-D). Direct adhesion assays further confirm that the enhanced coating stability and biofunction durability of the phosphonate-grafted, cRGD-PEGylated copolymer can considerably promote osteoblast attachment on HA surfaces, meanwhile preventing microbial adhesion. This research has resulted in a solution of self-assembly polymer structure optimization that exhibits stable nonfouling characteristics.

Intermediate analysis of magnesium alloy covered stent for a lateral aneurysm model in the rabbit common carotid artery.

OBJECTIVE: To analyze the outcomes of a magnesium alloy covered stent (MACS) for a lateral aneurysm model in common carotid artery (CCA). METHODS: In 32 rabbits, a MACS (group A, n = 17) or a Willis covered stent (WCS; group B, n = 15) was inserted and the rabbits were sacrificed 1, 3, 6, or 12 months after stenting. Angiography and intravascular ultrasound (IVUS) were performed at 3, 6, and 12 months. Scanning electron microscopy was performed for six stents in each group at 1, 3, and 6 months, and histopathology and histomorphology were conducted at 3 (n = 4), 6 (n = 4), and 12 (n = 12) months. RESULTS: Final angiography showed complete occlusion of the aneurysms in 12 cases. IVUS at 6 and 12 months revealed a significant increase in mean lumen area of the stented CCA in group A and also showed greater mean lumen area in group A than in group B. The endothelialization process was quicker in group A than in group B. CONCLUSION: MACS is effective for occlusion of lateral aneurysms and is superior to WCS in growth of the stented CCA and endothelialization. Further work is needed to make this device available for human use. KEY POINTS: • The MACS is an effective approach for occlusion of a lateral aneurysm. • IVUS showed that the CCA could grow following degradation of the MACS. • The lumen area of the stented CCA was excellent in MACS. • HE staining displayed the degradation of the magnesium alloy stent. • Combination of IVUS and DSA were applied in this study.

Influence of fluoride treatment on surface properties, biodegradation and cytocompatibility of Mg-Nd-Zn-Zr alloy.

Fluoride treatment is a commonly used technique or pre-treatment to optimize the degradation kinetic and improve the biocompatibility of magnesium-based implant. The influence of changed surface properties and degradation kinetics on subsequent protein adsorption and cytocompatibility is critical to understand the biocompatibility of the implant. In this study, a patent magnesium alloy Mg-Nd-Zn-Zr alloy (JDBM) designed for cardiovascular stent application was treated by immersion in hydrofluoric acid. A 1.5 µm thick MgF2 layer was prepared. The surface roughness was increased slightly while the surface zeta potential was changed to a much more negative value after the treatment. Static contact angle test was performed, showing an increase in hydrophilicity and surface energy after the treatment. The MgF2 layer slowed down in vitro degradation rate, but lost the protection effect after 10 days. The treatment enhanced human albumin adsorption while no difference of human fibrinogen adsorption amount was observed. Direct cell adhesion test showed many more live HUVECs retained than bare magnesium alloy. Both treated and untreated JDBM showed no adverse effect on HUVEC viability and spreading morphology. The relationship between changed surface characteristics, degradation rate and protein adsorption, cytocompatibility was also discussed.

[Finite element analysis for compression and expansion behavior of magnesium stent].

Magnesium stents have gained increasing interest as an ideal stent of future intervention. In order to study the deformation behavior of magnesium alloy stents in the interventional treatment, the finite element method was used to analysis the effects of different crimp and expansion dimensions on the mechanical properties (maximum stress, radial recoil rate, longitudinal shortening rate and radial strength). The results showed that crimping and expanding have a minimal influence on the stent radial strength. When the expansion size is same, the maximum equivalent stress and recoil rate decrease with the crimp size. When the crimp size is same, in contrast with the radial recoil rate, the maximum equivalent stress and longitudinal shortening rate increase with the expansion size. In addition the paper verified the radial strength-radial displacement curve obtained by FEM. Results are basically consistent, indicating the finite element method can efficiently provide researchers with reliable, high-quality design.

Anatomical Brushite-Coated Mg-Nd-Zn-Zr Alloy Cage Promotes Cervical Fusion: One-Year Results in Goats.

In this study, an anatomical brushite-coated Mg-Nd-Zn-Zr alloy cage was fabricated for cervical fusion in goats. The purpose of this study was to investigate the cervical fusion effect and degradation characteristics of this cage in goats. The Mg-Nd-Zn-Zr alloy cage was fabricated based on anatomical studies, and brushite coating was prepared. Forty-five goats were divided into three groups, 15 in each group, and subjected to C2/3 anterior cervical decompression and fusion with tricortical bone graft, Mg-Nd-Zn-Zr alloy cage, or brushite-coated Mg-Nd-Zn-Zr alloy cage, respectively. Cervical radiographs and computed tomography (CT) were performed 3, 6, and 12 months postoperatively. Blood was collected for biocompatibility analysis and Mg2+ concentration tests. The cervical spine specimens were obtained at 3, 6, and 12 months postoperatively for biomechanical, micro-CT, scanning electron microscopy coupled with energy dispersive spectroscopy, laser ablation-inductively coupled plasma-time-of-flight mass spectrometry, and histological analysis. The liver and kidney tissues were obtained for hematoxylin and eosin staining 12 months after surgery for biosafety analysis. Imaging and histological analysis showed a gradual improvement in interbody fusion over time; the fusion effect of the brushite-coated Mg-Nd-Zn-Zr alloy cage was comparable to that of the tricortical bone graft, and both were superior to that of the Mg-Nd-Zn-Zr alloy cage. Biomechanical testing showed that the brushite-coated Mg-Nd-Zn-Zr alloy cage achieved better stability than the tricortical bone graft at 12 months postoperatively. Micro-CT showed that the brushite coating significantly decreases the corrosion rate of the Mg-Nd-Zn-Zr alloy cage. In vivo degradation analysis showed higher Ca and P deposition in the degradation products of the brushite-coated Mg-Nd-Zn-Zr alloy cage, and no hyperconcentration of Mg was detected. Biocompatibility analysis showed that both cages were safe for cervical fusion surgery in goats. To conclude, the anatomical brushite-coated Mg-Nd-Zn-Zr alloy cage can promote cervical fusion in goats, and the brushite-coated Mg-Nd-Zn-Zr alloy is a potential material for developing absorbable fusion cages.

Biomimetic Porous Magnesium Alloy Scaffolds Promote the Repair of Osteoporotic Bone Defects in Rats through Activating the Wnt/ß-Catenin Signaling Pathway.

In this study, biomimetic porous magnesium alloy scaffolds were prepared to repair femoral bone defects in ovariectomized osteoporotic rats. The purpose of the study was to investigate the effect of biomimetic porous magnesium alloy scaffolds on repairing osteoporotic bone defects and possible mechanisms. The animal model of osteoporosis was established in female SD rats. Three months later, a bone defect of 3 mm in diameter and 3 mm in depth was created in the lateral condyle of the right femur. The rats were then randomly divided into two groups: an experimental group and a control group. Four weeks after surgery, gross specimens were observed and micro-CT scans were performed. The repair of osteoporotic femoral defects in rats was studied histologically using HE staining, Masson staining, and Goldner staining. The expression of Wnt5a, ß-catenin, and BMP-2 was measured between groups by immunohistochemical staining. The bone defect was repaired better after the application of biomimetic porous magnesium alloy scaffolds. Immunohistochemical results showed significantly higher expression of Wnt5a, ß-catenin, and BMP-2. To conclude, the biomimetic porous magnesium alloy scaffolds proposed in this paper might promote the repair of osteoporotic femoral bone defects in rats possibly through activating the Wnt/ß-catenin signaling pathway.

Brushite-coated Mg-Nd-Zn-Zr alloy promotes the osteogenesis of vertebral laminae through IGF2/PI3K/AKT signaling pathway.

Biodegradable magnesium (Mg) alloys have been extensively investigated in orthopedic implants due to their suitable mechanical strength and high biocompatibility. However, no studies have reported whether Mg alloys can be used to repair lamina defects, and the biological mechanisms regulating osteogenesis are not fully understood. The present study developed a lamina reconstruction device using our patented biodegradable Mg-Nd-Zn-Zr alloy (JDBM), and brushite (CaHPO4·2H2O, Dicalcium phosphate dihydrate, DCPD) coating was developed on the implant. Through in vitro and in vivo experiments, we evaluated the degradation behavior and biocompatibility of DCPD-JDBM. In addition, we explored the potential molecular mechanisms by which it regulates osteogenesis. In vitro, ion release and cytotoxicity tests revealed that DCPD-JDBM had better corrosion resistance and biocompatibility. We found that DCPD-JDBM extracts could promote MC3T3-E1 osteogenic differentiation via the IGF2/PI3K/AKT pathway. The lamina reconstruction device was implanted on a rat lumbar lamina defect model. Radiographic and histological analysis showed that DCPD-JDBM accelerated the repair of rat lamina defects and exhibited lower degradation rate compared to uncoated JDBM. Immunohistochemical and qRT-PCR results showed that DCPD-JDBM promoted osteogenesis in rat laminae via IGF2/PI3K/AKT pathway. This study shows that DCPD-JDBM is a promising biodegradable Mg-based material with great potential for clinical applications.

Biodegradable Zn-Cu-Mn alloy with suitable mechanical performance and in vitro degradation behavior as a promising candidate for vascular stents.

Recently, zinc (Zn) alloy has been considered as a promising biodegradable material due to its excellent physiological degradable behavior and acceptable biocompatibility. However, poor mechanical performance limits its application as vascular stents. In this study, novel biodegradable Zn-2.2Cu-xMn (x = 0.4, 0.7, and 1.0 wt%) alloys with suitable mechanical performance were investigated. The effects of Mn addition on microstructure, mechanical properties, and in vitro degradation of Zn-2.2Cu-xMn alloys were systematically investigated. After adding Mn, dynamic recrystallization (DRX) during hot extrusion was promoted, resulting in slightly finer grain size, higher DRXed regions ratio, and weaker texture. And volume fraction and number density of second phase precipitates (micron, submicron, and nano-sized ε and MnZn13 phase) and the concentration of (Cu, Mn) in the matrix were increased. Therefore, Zn-2.2Cu-xMn alloys exhibited suitable mechanical performances (strength >310 MPa, elongation >30%) mainly due to the combination effects of grain refinement, solid solution strengthening, second phase precipitation hardening, and texture weakening. Moreover, the alloys maintained good stability of mechanical properties within 18 months and good elongation over 15% even at a high strain rate of 0.1 s-1. In addition, the alloys presented appropriate in vitro degradation rates in a basically uniform degradation mode and acceptable in vitro cytocompatibility. The above results indicated that the newly designed biodegradable Zn-2.2Cu-0.4Mn alloy with suitable comprehensive mechanical properties, appropriate degradation behavior, and acceptable cytocompatibility is a promising candidate for vascular stents.

Fabrication and characterization of biodegradable Zn-Cu-Mn alloy micro-tubes and vascular stents: Microstructure, texture, mechanical properties and corrosion behavior.

Zinc (Zn) alloys are a promising biodegradable material for vascular stent applications. This study aimed to fabricate biodegradable Zn-2.0Cu-0.5Mn alloy micro-tubes and vascular stents with high dimensional accuracy and suitable mechanical properties, and to investigate their microstructure, texture, mechanical properties and corrosion behavior. The micro-tubes and vascular stents were successfully fabricated by a combined process of extrusion, drawing, laser cutting and electrochemical polishing. The microstructures of as-extruded and as-drawn micro-tubes consisted of Zn matrix with near-equiaxed grains (average grain size: ∼2 µm) and second phases of ε (CuZn4) and MnZn13 with different sizes. The texture evolved from basal planes approximately paralleling to deformation direction for as-extruded micro-tube to approximately perpendicular to deformation direction for as-drawn micro-tube, because predominant deformation mechanisms changed from basal dislocation slip during tube extrusion to prismatic dislocation, pyramidal dislocations, and {101¯2} twins during tube drawing. As-drawn micro-tube exhibited suitable mechanical properties with an ultimate tensile strength of about 298 MPa and elongation of about 26% as a stent material. Moreover, the processed stent with a thickness of about 125 µm possessed sufficient radial strength of about 150 kPa and good balloon expandability. In addition, as-drawn tube exhibited an in vitro corrosion rate of about 158 µm/year with a basically uniform corrosion morphology. These results indicated that biodegradable Zn-2.0Cu-0.5Mn alloy is a promising vascular stent material candidate, and the procedure for processing the micro-tube and stent is practical and effective. STATEMENT OF SIGNIFICANCE: Fabrication of micro-tubes followed by laser cutting and polishing is a common way to prepare metallic vascular stents. However, it is quite challenging to fabricate Zn-based stents using this standard method, and there is a lack of studies reporting processing details in the past. Biodegradable Zn-2.0Cu-0.5Mn alloy micro-tubes and vascular stents with high dimensional accuracy and suitable mechanical properties were successfully fabricated by a combined process in this study. As-drawn micro-tube exhibited an ultimate tensile strength of about 298 MPa and elongation of about 26%. The stent possessed sufficient radial strength of about 150 kPa and good balloon expandability. We demonstrated a practical method to fabricate biodegradable Zn-based micro-tubes and stents with high dimensional accuracy and mechanical properties.

The effects of alignment and diameter of electrospun fibers on the cellular behaviors and osteogenesis of BMSCs.

Electrospun fiber scaffolds, due to their mimicry of bone extracellular matrix (ECM), have become an important biomaterial widely applied in bone tissue engineering in recent years. While topographic cues of electrospun membranes such as alignment and diameter played vital roles in determining cellular behaviors. Yet few researches about the effects of these two significant parameters on osteogenesis have been reported. Thus, the present work explored the influence of aligned and random poly (L-lactic acid) (PLLA) fiber matrices with diameters of nanoscale (0.6 µm) and microscale (1.2 µm), respectively, on cellular responses of bone marrow mesenchymal stem cells (BMSCs), such as cell adhesion, migration, proliferation and osteogenesis. Our results revealed that aligned nanofibers (AN) could affect cell morphology and promote the migration of BMSCs after 24 h of cell culturing. Besides, AN group was observed to possess excellent biocompatibility and have significantly improved cell growth comparing with random nanofibers. More importantly, in vitro osteogenesis researches including ALP and Alizarin Red S staining, qRT-PCR and immunofluorescence staining demonstrated that BMSCs culturing on AN group exhibited higher osteogenic induction proficiency than that on aligned microfibers (AM) and random fiber substrates (RN and RM). Accordingly, aligned nanofiber scaffolds have greater application potential in bone tissue engineering.

Fatigue and dynamic biodegradation behavior of additively manufactured Mg scaffolds.

Additive manufacturing (AM) has enabled the fabrication of biodegradable porous metals to satisfy the desired characteristics for orthopedic applications. The geometrical design on AM biodegradable metallic scaffolds has been found to offer a favorable opportunity to regulate their mechanical and degradation performance in previous studies, however mostly confined to static responses. In this study, we presented the effect of the geometrical design on the dynamic responses of AM Mg scaffolds for the first time. Three different types of porous structures, based on various unit cells (i.e., biomimetic, diamond, and sheet-based gyroid), were established and then subjected to selective laser melting (SLM) process using group-developed Mg-Nd-Zn-Zr alloy (JDBM) powders. The topology after dynamic electropolishing, dynamic compressive properties, and dynamic biodegradation behavior of the AM Mg scaffolds were comprehensively evaluated. It was found that dynamic electropolishing effectively removed the excessive adhered powders on the surfaces and resulted in similar geometrical deviations amongst the AM Mg scaffolds, independent of their porous structures. The geometrical design significantly affected the compressive fatigue properties of the AM Mg scaffolds, of which the sheeted-based gyroid structure demonstrated a superior fatigue endurance limit of 0.85 at 106 cycles. Furthermore, in vitro dynamic immersion behaviors of the AM Mg scaffolds revealed a decent dependence on local architectures, where the sheeted-based gyroid scaffold experienced the lowest structural loss with a relatively uniform degradation mode. The obtained results indicate that the geometrical design could provide a promising strategy to develop desirable bone substitutes for the treatment of critical-size load-bearing defects. STATEMENT OF SIGNIFICANCE: Additive manufacturing (AM) has provided unprecedented opportunities to fabricate geometrically complex biodegradable scaffolds where the topological design becomes a key determinant on comprehensive performance. In this paper, we fabricate 3 AM biodegradable Mg scaffolds (i.e., biomimetic, diamond, and sheet-based gyroid) and report the effect of the geometrical design on the dynamic responses of AM Mg scaffolds for the first time. The results revealed that the sheeted-based gyroid scaffold exhibited the best combination of superior compressive fatigue properties and relatively uniform dynamic biodegradation mode, suggesting that the regulation of the porous structures could be an effective approach for the optimization of AM Mg scaffolds as to satisfy clinical requirements in orthopedic applications.

Effects of composition and hierarchical structures of calcium phosphate coating on the corrosion resistance and osteoblast compatibility of Mg alloys.

Magnesium and its alloys have been recently used in biomedical applications such as orthopedic implants, whereas the weak corrosion resistance undermines their clinical efficacy. Herein, to address this critical challenge, the preparation of hierarchically structured hydroxyapatite-based coatings was proposed. Compact coatings were fabricated on a Mg alloy through a facile two-step method of chemical deposition of brushite precursor and subsequent hydrothermal conversion. A series of HA-based coatings were obtained with kinetic conversion process with formation mechanism revealed. The hydroxyapatite coating demonstrated the greatest corrosion resistance for Mg in electrochemical and long-term immersion tests, especially against pitting corrosion, attributable to its compact structure, alkaline degradation environment and self-induced growth capacity. The in vitro cytocompatibility and osteoinductivity were dictated. Additionally, anti-corrosion mechanisms were compared among different coating compositions and structures, along with their correlation with cellular response. Our study brings hints for a tailored surface design for resorbable biomedical device applications.

A Biomimetic Zinc Alloy Scaffold Coated with Brushite for Enhanced Cranial Bone Regeneration.

Bone tissue engineering is considered as a promising pathway for bone regeneration and defect reconstruction, in which scaffolds play an important role. Zn alloy, which is a biodegradable metal material that has advantages of metallic and biodegradable characteristics, has its special features, especially the ideal degradation rate and acceptable biocompatibility, which make it worthy to be further investigated for medical applications. In this study, new biodegradable porous Zn alloy scaffolds with Ca-P coating were attempted to repair cranial bone defect, and in vitro and in vivo assays were conducted to evaluate its biocompatibility, osteo-inductivity, and osteo-conductivity. The results indicated that coated Zn alloy possessed good biocompatibility, with no cytotoxicity. It could also promote osteogenic differentiation and calcium deposition of rabbit BMSCs in vitro, and new bone formation around the scaffold in vivo. The biodegradable porous Zn alloy scaffold with Ca-P coating is considered to be promising in cranial bone defect repair.

Biodegradable JDBM coating stent has potential to be used in the treatment of benign biliary strictures.

In our previous study, to find out the optimal alloy suitable for biliary surgery, magnesium alloy Jiao Da Bio-magnesium (denoted as JDBM) alloy, Zn-3Cu alloys, and their respective coating (MgF2-PDLLA) products were produced for our research. We found that JDBM seems to be a potential material for clinical biliary stent application due to its uniform degradation and good compatibility. In order to apply the JDBM alloy to treat benign bile duct stricture, our group prepared the bare JDBM and its coating product into finished stents by mesh weaving carving technology and conducted the mechanical property tests, degradation tests and biocompatibility tests. During the mechanical property tests, we found the bare JDBM stent was more suitable than titanium alloy stent when applies to the bile duct, and the coating of the JDBM coating stent has no effect on its mechanical properties. Our in vitro and in vivo experiments revealed that the degradation rate of the JDBM coating stent is lower than that of the JDBM stent, and both stents were biosafe. Thus, there is promise for JDBM coating stents for the treatment of benign biliary strictures.

Biosafety and efficacy evaluation of a biodegradable magnesium-based drug-eluting stent in porcine coronary artery.

Although the drug-eluting stent (DES) has become the standard for percutaneous coronary intervention (PCI)-based revascularization, concerns remain regarding the use of DES, mainly due to its permanent rigid constraint to vessels. A drug-eluting bioresorbable stent (BRS) was thus developed as an alternative to DES, which can be absorbed entirely after its therapeutic period. Magnesium (Mg)-based BRSs have attracted a great deal of attention due to their suitable mechanical properties, innovative chemical features, and well-proven biocompatibility. However, the primary disadvantage of Mg-based BRSs is the rapid degradation rate, resulting in the early loss of structural support long before the recovery of vascular function. Recently, a new type of patented Mg-Nd-Zn-Zr alloy (JDBM) was developed at Shanghai Jiao Tong University to reduce the degradation rate compared to commercial Mg alloys. In the present investigation, a poly(D,L-lactic acid)-coated and rapamycin eluting (PDLLA/RAPA) JDBM BRS was prepared, and its biosafety and efficacy for coronary artery stenosis were evaluated via in vitro and in vivo experiments. The degree of smooth muscle cell adhesion to the PDLLA/RAPA coated alloy and the rapamycin pharmacokinetics of JDBM BRS were first assessed in vitro. JDBM BRS and commercial DES FIREHAWK were then implanted in the coronary arteries of a porcine model. Neointimal hyperplasia was evaluated at 30, 90, and 180 days, and re-endothelialization was evaluated at 30 days. Furthermore, Micro-CT and optical coherence tomography (OCT) analyses were performed 180 days after stent implantation to evaluate the technical feasibility, biocompatibility, and degradation characteristics of JDBM BRS in vivo. The results show the ability of a PDLLA/RAPA coated JDBM to inhibit smooth muscle cell adhesion and moderate the drug release rate of JDBM BRS in vitro. In vivo, low local and systemic risks of JDBM BRS were demonstrated in the porcine model, with preserved mechanical integrity after 6 months of implantation. We also showed that this novel BRS was associated with a similar efficacy profile compared with standard DES and high anti-restenosis performance. These findings may confer long term advantages for using this BRS over a traditional DES.

Biodegradable Zn-1.5Cu-1.5Ag alloy with anti-aging ability and strain hardening behavior for cardiovascular stents.

Zn and its alloys are considered as a new class of biodegradable metals due to their moderate degradation rates and acceptable biocompatibility. However, inadequate mechanical properties limit their further applications, especially for cardiovascular stents. In this study, a novel biodegradable Zn-1.5Cu-1.5Ag (wt%) alloy with excellent mechanical properties was developed, and then its in vitro degradation and cytotoxicity were characterized. Microstructural characterization showed that hot extrusion produced a bimodal distribution of grain size and much finer secondary phase precipitates. The as-extruded alloy exhibited a satisfactory combination of strength and plasticity (yield strength: 162.0 ± 2.94 MPa, ultimate tensile strength: 220.3 ± 1.70 MPa and elongation: 44.13 ± 1.09%). After being aged at room temperature for 8 months, its mechanical properties increased about 10%, implying its good anti-aging ability. The strain hardening exponent (n) calculated from true stress-strain curve showed that this alloy has evident strain hardening. Immersion tests in c-SBF solution revealed that this alloy has a moderate corrosion rate (48.6 ± 4.14 µm/year) and slightly localized corrosion behavior. Electrochemical tests showed that a weak passive film formed on surface during degradation, which has a limited protective effect. The cytotoxicity tests exhibited that this alloy possesses acceptable in vitro biocompatibility, which is comparable to pure Zn. According to the results of mechanical properties, corrosion behavior and cytotoxicity, the Zn-1.5Cu-1.5Ag alloy can be regarded as a potential candidate for cardiovascular stent applications.

In vitro cytocompatibility, hemocompatibility and antibacterial properties of biodegradable Zn-Cu-Fe alloys for cardiovascular stents applications.

In the present study, the effects of Zn-3Cu-xFe (x = 0, 0.2, 0.5 wt%) alloys on endothelial cells (EA.hy926) and smooth muscle cells (A7r5), the hemocompatibility and antibacterial properties were also evaluated. The cell viability of EA.hy926 cells and A7r5 cells decreased with the increasing of extract concentration. At the same Zn2+ concentration (over 6 ppm), the cell viability of EA.hy926 cells increased with the addition of Cu or Cu and Fe content, but no significant effect on A7r5 cells was observed. The hemolysis rate of Zn-3Cu-xFe alloys samples was about 1%, and there was no adversely affected on platelets adhering to the surface of the Zn alloys. As Fe content increases in the Zn-Cu-Fe alloys, the antibacterial lower concentrations against Staphylococcus aureus and Escherichia coli was improved due to the higher degradation rate and more Zn2+ and Cu2+ released. Our previous study already showed that the Zn-Cu-Fe alloy exhibited excellent mechanical properties and moderate degradation rate. Based on the above results, the in vitro biocompatibilities and antibacterial properties of Zn-3Cu alloy are significantly improved by the alloying of trace Fe, and the hemocompatibility is not adversely affected, which indicated that Zn-Cu-Fe alloy is a promising vascular stents candidate material.

Simultaneous enhancement of anti-corrosion, biocompatibility, and antimicrobial activities by hierarchically-structured brushite/Ag3PO4-coated Mg-based scaffolds.

Development of bone graft substitutes with appropriate integration of mechanical, biodegradable, and biofunctional properties, which promote bone formation while simultaneously preventing implant-associated infections, remains a great challenge. Herein we designed and synthesized a brushite/Ag3PO4-coated Mg-Nd-Zn-Zr scaffolds through chemical solution deposition of a composite coating onto the fluorinated Mg-based scaffolds generated with template replication method. The coated Mg-based open-porous scaffolds exhibit hierarchically-structured surface with cube-shaped Ag3PO4 nanoparticles uniformly distributed on top of microsized brushite grains. Immersion test reveals that the initial degradation rate of the coated scaffolds could be reduced by ~81% compared to the original scaffolds. The mean corrosion rate in 4 weeks falls into 0.10-0.15 mm/year to meet clinical requirements. The compatibility and ALP activity of cells grown in the extracts from the coated Mg-based scaffolds were increased compared with Ti control and original scaffolds, mainly due to the favorable microenvironment generated by Mg biodegradation. Besides, the coated Mg-based scaffold demonstrated potent antimicrobial activity via the synergistic actions of alkaline degradation products of Mg and the Ag species in the coating, achieving >99.5% antibacterial rate against both gram-positive and gram-negative bacteria with relatively low silver content. Taken together, this study presents a new candidate of brushite/Ag3PO4-coated Mg-based scaffold with appropriate degradation characteristics, cytocompatibility, and antimicrobial activities for bone tissue engineering applications.

The bioeffects of degradable products derived from a biodegradable Mg-based alloy in macrophages via heterophagy.

Biodegradable magnesium alloys are promising candidates for use in biomedical applications. However, degradable particles (DPs) derived from Mg-based alloys have been observed in tissue in proximity to sites of implantation, which might result in unexpected effects. Although previous in vitro studies have found that macrophages can take up DPs, little is known about the potential phagocytic pathway and the mechanism that processes DPs in cells. Additionally, it is necessary to estimate the potential bioeffects of DPs on macrophages. Thus, in this study, DPs were generated from a Mg-2.1Nd-0.2Zn-0.5Zr alloy (JDBM) by an electrochemical method, and then macrophages were incubated with the DPs to reveal the potential impact. The results showed that the cell viability of macrophages decreased in a concentration-dependent manner in the presence of DPs due to effects of an apoptotic pathway. However, the DPs were phagocytosed into the cytoplasm of macrophages and further degraded in phagolysosomes, which comprised lysosomes and phagosomes, by heterophagy instead of autophagy. Furthermore, several pro-inflammatory cytokines in macrophages were upregulated by DPs through the induction of reactive oxygen species (ROS) production. To the best of our knowledge, this is the first study to show that DPs derived from a Mg-based alloy are consistently degraded in phagolysosomes after phagocytosis by macrophages via heterophagy, which results in an inflammatory response owing to ROS overproduction. Thus, our research has increased the knowledge of the metabolism of biodegradable Mg metal, which will contribute to an understanding of the health effects of biodegradable magnesium metal implants used for tissue repair. STATEMENT OF SIGNIFICANCE: Biomedical degradable Mg-based alloys have great promise in applied medicine. Although previous studies have found that macrophages can uptake degradable particles (DPs) in vitro and observed in the sites of implantation in vivoin vivo, few studies have been carried out on the potential bioeffects relationship between DPs and macrophages. In this study, we analyzed the bioeffects of DPs derived from a Mg-based alloy on the macrophages. We illustrated that the DPs were size-dependently engulfed by macrophages via heterophagy and further degraded in the phagolysosome rather than autophagosome. Furthermore, DPs were able to induce a slight inflammatory response in macrophages by inducing ROS production. Thus, our research enhances the knowledge of the interaction between DPs of Mg-based alloy and cells, and offers a new perspective regarding the use of biodegradable alloys.

Degradation and osteogenic induction of a SrHPO4-coated Mg-Nd-Zn-Zr alloy intramedullary nail in a rat femoral shaft fracture model.

Magnesium and Mg-based alloys are promising biomaterials for orthopedic implants because of their degradability, osteogenic effects, and biocompatibility. However, the drawbacks of these materials include high hydrogen gas production, unexpected corrosion resistance, and insufficient mechanical strength duration. Surface modification can protect these biomaterials and induce osteogenesis. In this work, a SrHPO4 coating was developed for our patented biodegradable Mg-Nd-Zn-Zr alloy (abbr. JDBM) through a chemical deposition method. The coating was characterized by in vitro immersion, ion release, and cytotoxicity tests, which showed a slower corrosion behavior and excellent cell viability. RNA sequencing of MC3T3E1 cells treated with SrHPO4-coated JDBM ion release test extract showed increased Tlr4, followed by the activation of the downstream PI3K/Akt signaling pathway, causing proliferation and growth of pre-osteoblasts. An intramedullary nail (IMN) was implanted in a femoral fracture rat model. Mechanical test, radiological and histological analysis suggested that SrHPO4-coated JDBM has superior mechanical properties, induces more bone formation, and decreases the degradation rate compared with uncoated JDBM and the administration of TLR4 inhibitor attenuated the new bone formation for fracture healing. SrHPO4 is a promising coating for JDBM implants, particularly for long-bone fractures.