Keratin Formed Bioadhesive Ophthalmic Gel for the Bacterial Conjunctivitis Treatment.

Keratin has the potential to function as the gel matrix in an ophthalmic formulation for the encapsulation of the macrolide antibiotic azithromycin. The quality of this formulation was thoroughly evaluated through various analyses, such as in vitro release assessment, rheological examination, intraocular retention studies in rabbits, assessment of bacteriostatic efficacy, and safety evaluations. It is worth mentioning that the gel demonstrated shear thinning properties and exhibited characteristics of an elastic solid, thereby confirming its structural stability. The gel demonstrated a notable affinity for mucosal surfaces in comparison to traditional azithromycin aqueous solutions. In vitro release testing revealed that drug release transpired via diffusion mechanisms, following a first-order kinetic release pattern. Additionally, the formulated gel exhibited remarkable antibacterial efficacy against Staphylococcus aureus and Pseudomonas aeruginosa in bacteriostatic evaluations. Lastly, safety assessments confirmed that the gel eye drops induced minimal irritation and displayed no apparent cytotoxicity, indicating their good safety and biocompatibility for ocular application. Thus, these findings indicated that the prepared azithromycin gel eye drops complied with the requisite standards for ophthalmic preparations.

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.

Mg-based implants with a sandwiched composite coating simultaneously facilitate antibacterial and osteogenic properties.

Insufficient antibacterial effects and over-fast degradation are the main limitations of magnesium (Mg)-based orthopedic implants. In this study, a sandwiched composite coating containing a triclosan (TCS)-loaded poly(lactic acid) (PLA) layer inside and brushite (DCPD) layer outside was prepared on the surface of the Mg-Nd-Zn-Zr (denoted as JDBM) implant. In vitro degradation tests revealed a remarkable improvement in the corrosion resistance and moderate degradation rate. The drug release profile demonstrated a controllable and sustained TCS release for at least two weeks in vitro. The antibacterial rates of the implant were all over 99.8% for S. aureus, S. epidermidis, and E. coli, demonstrating superior antibacterial effects. Additionally, this coated JDBM implant exhibited no cytotoxicity but improved cell adhesion and proliferation, indicating excellent cytocompatibility. In vivo assays were conducted by implant-related femur osteomyelitis and osseointegration models in rats. Few bacteria were attached to the implant surface and the surrounding bone tissue. Furthermore, the coated JDBM implant exhibited more new bone formation than other groups due to the synergistic biological effects of released TCS and Mg2+, revealing excellent osteogenic ability. In summary, the JDBM implant with the sandwiched composite coating could significantly enhance the antibacterial activities and osteogenic properties simultaneously by the controllable release of TCS and Mg2+, presenting great potential for clinical transformation.

Hundred-femtosecond-level concise optical time delay measurement system based on linear optical sampling.

Fiber-delay measurement is one of the key fundamental technologies in numerous fields. Here, we propose and experimentally demonstrate a high-precision and concise optical time delay measurement system based on the technique of linear optical sampling, reaching the precision better than 100 fs under averaging. The use of only two optical frequency combs without locking the carrier-envelope-offset frequency greatly simplifies the structure of the time-delay measurement system. We also experimentally investigate the current limitations on the precision of the system. The timing jitter noises of two sources are mainly non-common mode and are both restricted to the frequency sources. Our results indicate that the proposed device can measure fiber length fluctuations below 10 µm, paving the way for further analyses of the external disturbances on the fiber link.

Selective Characterization of Olefins by Paternò-Büchi Reaction with Ultrahigh Resolution Mass Spectrometry.

Petroleum olefins play important roles in various secondary processing procedures and are important feedstocks for the modern organic chemical industry. It is quite challenging to analyze petroleum olefins beyond the gas chromatography (GC)-able range using mass spectrometry (MS) due to the difficulty of soft ionization and the matrix complexity. In this work, a Paternò-Büchi (PB) reaction combined with atmospheric pressure chemical ionization and ultrahigh resolution mass spectrometry (APCI-UHRMS) was developed for selective analysis of olefins. Through the PB reaction, C═C bonds were transformed into four-membered rings of oxetane with improved polarity so that soft ionization of olefins could be achieved. The systematic optimization of PB reaction conditions, as well as MS ionization conditions, ensured a high reaction yield and a satisfied MS response. Furthermore, a sound scheme was set up to discriminate the coexisting unsaturated alkanes in complex petroleum, including linear olefins, nonlinear olefins, cycloalkanes, and aromatics, making use of their different behaviors during the PB reaction and chemical ionization. The developed strategy was successfully applied to the analysis of olefins in fluid catalytic cracking oil slurry, a complex heavy oil sample. This method extended the characterization of petroleum olefins from lower to higher with high efficiency and selectivity to provide a comprehensive molecular library for heavy petroleum samples and process optimization.

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.

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.

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.

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.

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.

Research and development strategy for biodegradable magnesium-based vascular stents: a review.

Magnesium alloys are an ideal material for biodegradable vascular stents, which can be completely absorbed in the human body, and have good biosafety and mechanical properties. However, the rapid corrosion rate and excessive localized corrosion, as well as challenges in the preparation and processing of microtubes for stents, are restricting the clinical application of magnesium-based vascular stents. In the present work we will give an overview of the recent progresses on biodegradable magnesium based vascular stents including magnesium alloy design, high-precision microtubes processing, stent shape optimisation and functional coating preparation. In particular, the Triune Principle in biodegradable magnesium alloy design is proposed based on our research experience, which requires three key aspects to be considered when designing new biodegradable magnesium alloys for vascular stents application, i.e. biocompatibility and biosafety, mechanical properties, and biodegradation. This review hopes to inspire the future studies on the design and development of biodegradable magnesium alloy-based vascular stents.

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.

Mg-based bone implants show promising osteoinductivity and controllable degradation: A long-term study in a goat femoral condyle fracture model.

In this work, the in vivo biocompatibility and biodegradation behavior of Mg-Nd-Zn-Zr alloy (denoted as JDBM) screws were studied using a goat femoral condyle fracture model. Blood analysis indicates that the liver and kidney functions of goats were not affected by JDBM, JDBM coated with brushite (denoted as JDBM-DCPD) and PLA implants. Radiographic analysis shows that JDBM-DCPD screw has lower degradation rate than JDBM. Histological images show that compared with PLA, JDBM and JDBM-DCPD show superior effect to promote more new bone formation. JDBM-DCPD group has more new bone formation than JDBM group, indicating good osteoinductivity of DCPD coating. JDBM group show higher osteogenic factors level (BMP2, ALP and OC) in peri-implant callus tissue than PLA group. Long-term (18months) in vivo implants Micro-CT result shows that the degradation of JDBM-DCPD screw may be slower than desirable, and the thickness of DCPD coating could be further adjusted to match the degradation to the bone recovery.

Potential biodegradable Zn-Cu binary alloys developed for cardiovascular implant applications.

Binary Zn-Cu alloy system is developed as potential biodegradable materials for cardiovascular implant application. The microstructure, tensile properties, in vitro corrosion behavior, cytotoxicity and antibacterial property of as-extruded Zn-xCu (x=1, 2, 3, and 4wt%) alloys are investigated systematically. It shows that as Cu content increases more CuZn5 phase precipitates. After extrusion, the CuZn5 phases are broken and the grains of Zn-xCu alloys are refined. Tensile test shows that Cu addition could significantly improve the mechanical properties of Zn-xCu alloys. Particularly, the elongation of the Zn-4Cu reaches 50.6±2.8%, which could facilitate the micro-tubes processing for stent fabrication. The micro-tubes of 3mm in outer diameter and 0.2mm in thickness as well as vascular stents have been fabricated successfully using the Zn-Cu binary alloy. The degradation rates of Zn-xCu alloys in c-SBF solution are quite low, which vary from 22.1±4.7 to 33.0±1.0µmyear-1. With increasing Cu concentration, the corrosion rates of the Zn-xCu alloys generally exhibit a little increase compared with pure Zn, which show no significant difference among Zn-xCu alloys. In vitro test shows that Zn-xCu alloys exhibit acceptable cytotoxicity to human endothelial cells and the antibacterial property (S. aureus) is perfect when Cu concentration is higher than 2wt%. Therefore, the newly developed Zn-xCu binary alloys could be promising candidates for biodegradable cardiovascular implant application due to their excellent combination of strength and ductility, low degradation rates, acceptable cytotoxicity and good antibacterial property.

Facile Preparation of Poly(lactic acid)/Brushite Bilayer Coating on Biodegradable Magnesium Alloys with Multiple Functionalities for Orthopedic Application.

Recently magnesium and its alloys have been proposed as a promising next generation orthopedic implant material, whereas the poor corrosion behavior, potential cytotoxicity, and the lack of efficient drug delivery system have limited its further clinical application, especially for the local treatment of infections or musculoskeletal disorders and diseases. In this study, we designed and developed a multifunctional bilayer composite coating of poly(lactic acid)/brushite with high interfacial bonding strength on a Mg-Nd-Zn-Zr alloy, aiming to improve the biocorrosion resistance and biocompatibility of the magnesium-based substrate, as well as to further incorporate the biofunctionality of localized drug delivery. The composite coating consisted of an inner layer of poly(lactic acid) serving as a drug carrier and an outer layer composed of brushite generated through chemical solution deposition, where a facile pretreatment of UV irradiation was applied to the poly(lactic acid) coating to facilitate the heterogeneous nucleation of brushite. The in vitro degradation results of electrochemical measurements and immersion tests indicated a considerable reduction of magnesium degradation provided the composite coating. A systematic investigation of cellular response with cell viability, adhesion, and ALP assays confirmed the coated Mg alloy induced no toxicity to MC3T3-E1 osteoblastic cells but rather fostered cell attachment and proliferation and promoted osteogenic differentiation, revealing excellent biosafety and biocompatibility and enhanced osteoinductive potential. An in vitro drug release profile of paclitaxel from the composite coating was monitored with UV-vis spectroscopy, showing an alleviated initial burst release and a sustained and controlled release feature of the drug-loaded composite coating. These findings suggested that the bilayer poly(lactic acid)/brushite coating provided effective protection for Mg alloy, greatly enhanced cytocompatibility and bioactivity, and, moreover, possessed local drug delivery capability; hence magnesium alloy with poly(lactic acid)/brushite coating presents great potential in orthopedic clinical applications, especially for localized bone therapy.

Enhanced corrosion resistance and cytocompatibility of biodegradable Mg alloys by introduction of Mg(OH)2 particles into poly (L-lactic acid) coating.

A strategy of suppressing the fast degradation behaviour of Mg-based biomaterials by the introduction of one of Mg degradation products Mg(OH)2 was proposed according to the following degradation mechanism, Mg + 2H2O ⇋ Mg(OH)2 + H2↑. Specifically, Mg(OH)2 submicron particles were mixed into poly (L-lactic acid) (PLLA) to synthesize a composite coating onto hydrofluoric acid-pretreated Mg-Nd-Zn-Zr alloy. The in vitro degradation investigations showed that the addition of Mg(OH)2 particles not only slowed down the corrosion of Mg matrix, but also retarded the formation of gas pockets underneath the polymer coating. Correspondingly, cytocompatibility results exhibited significant improvement of proliferation of endothelial cells, and further insights was gained into the mechanisms how the introduction of Mg(OH)2 particles into PLLA coating affected the magnesium alloy degradation and cytocompatibility. The present study provided a promising surface modification strategy to tailor the degradation behaviour of Mg-based biomaterials.

Research on a Zn-Cu alloy as a biodegradable material for potential vascular stents application.

Zn-based alloys have been viewed as new potential materials for biodegradable implants, such as cardiovascular stents, mainly in consideration of their lower corrosion rate when compared with that of Mg alloys. In this study we developed a new Zinc-4wt.%Copper (Zn-4Cu) alloy as a biodegradable material. Hot extrusion was applied to Zn-4Cu to refine the microstructure and consequently improve its mechanical properties and corrosion resistance. After extrusion, dendritic CuZn5 phases were broken and distributed along the extrusion direction. The grains were refined obviously due to dynamical recrystallization. The yield strength (YS), ultimate tensile strength (UTS) and elongation of the as-extruded alloy are 250±10MPa, 270±10MPa and 51±2%, respectively. The corrosion rate of the as-extruded alloy in Hank's solution is about 9.41(±1.34)µmyear(-1). In vitro evaluation shows that Zn-4Cu presents acceptable toxicity to human endothelial cells, and could effectively inhibit bacteria adhesion and biofilm formation. The present study indicates that the as-extruded Zn-4Cu alloy exhibits excellent strength and ductility, uniform and slow degradation, good biocompatibility and significant antibacterial effect, which make it an excellent candidate material for biodegradable implants, especially for cardiovascular stents application.

Effect of macrophages on in vitro corrosion behavior of magnesium alloy.

The influence of cells on the corrosion behavior of biomedical magnesium alloy is an important but less studied topic, which is helpful for understanding the inconsistent corrosion rates between in vitro and in vivo experiments. In this work, macrophages were directly cultured on Mg-2.1Nd-0.2Zn-0.5Zr (wt %, abbreviated as JDBM) alloy surface for 72 or 168 hours. Macrophages retained good viability and the generation of reactive oxygen species (ROS) was greatly promoted on the alloy. Weight loss, Mg(2+) concentration, and cross-section observation results demonstrated that macrophages accelerated the in vitro corrosion of JDBM. The coverage of cell body did not affect the local thickness of corrosion product layer. The corrosion product layer had a porous inner Mg(OH)2 layer and a dense outer layer mainly composed of O, P, Mg, and Ca. The uniform acceleration of JDBM corrosion was attributed to the omnidirection diffusion of ROS from macrophages. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2476-2487, 2016.