Study on the Bioactivity Response of the Newly Developed Zn-Cu-Mn/Mg Alloys for Biodegradable Implant Application.

Scaffolds play a crucial role in bone tissue engineering to support the defect area through bone regeneration and defect reconstruction. Promising tissue regeneration without negative repercussions and avoidance of the lifelong presence inside the body make bioresorbable metals prosper in the field of regenerative medicine. Recently, Zn and its alloys have emerged as promising biodegradable materials for their moderate degradation rate and satisfactory biocompatibility. Nevertheless, it is very challenging for cells to adhere and grow over the Zn surface alone, which influences the tissue-implant integration. In this study, an attempt has been made to systematically investigate the bioactivity responses in terms of in vitro hemocompatibility, cytotoxicity, antibacterial activity, and in vivo biocompatibility of newly developed Zn-2Cu-0.5Mn/Mg alloy scaffolds with different surface roughness. The rough surface of Zn-2Cu-0.5Mg shows the highest degradation rate of 0.16 mm/yr. The rough surface exhibits a prominent role in the adsorption of protein, further enhancing cell adhesion. Concentration-dependent alloy extract shows the highest cell proliferation for 12.5% of the extract with a maximum cell viability of 101% in Zn-2Cu-0.5Mn and 108% in Zn-2Cu-0.5Mg after 3 d. Acceptable hemolysis percentages (less than 5%) with promising anticoagulation properties are observed for all of the conditions. Enhanced antibacterial (Staphylococcus aureus and Escherichia coli) activity due to a significant effect of ions illustrates the maximum killing effect on the bacterial colony for the rough Zn-2Cu-0.5Mg alloy. In addition, it is observed that for rough Zn-2Cu-0.5Mn/Mg alloys, the inflammatory response is minimal after subcutaneous implantation, and neo-bone tissue forms in the defect areas of the rat femur with satisfactory biosafety response. The osseointegration property of the Zn-2Cu-0.5Mg alloy is comparable to that of the Zn-2Cu-0.5Mn alloy. Therefore, the rough surface of the Zn-2Cu-0.5Mg alloy has the potential to enhance biocompatibility and promote better osseointegration activity with host tissues for various biomedical applications.

Feasibility Insights of the Green-Assisted Calcium-Phosphate Coating on Biodegradable Zinc Alloys for Biomedical Application: In Vitro and In Vivo Studies.

In the field of bone tissue engineering, recently developed Zn alloy scaffolds are considered potential candidates for biodegradable implants for bone regeneration and defect reconstruction. However, the clinical success of these alloys is limited due to their insufficient surface bioactivities. Further, the higher concentration of Zn2+ produced during degradation promotes antibacterial activity, but deteriorates osteogenic properties. This study fabricated an Azadirachta indica (neem)-assisted brushite-hydroxyapatite (HAp) coating on the recently developed Zn-2Cu-0.5Mg alloy to tackle the above dilemma. The microstructure, degradation behavior, antibacterial activity, and hemocompatibility, along with in vitro and in vivo cytocompatibility of the coated alloys, are systematically investigated. Microstructural analysis reveals flower-like morphology with uniformly grown flakes for neem-assisted deposition. The neem-assisted deposition significantly improves the adhesion strength from 12.7 to 18.8 MPa, enhancing the mechanical integrity. The potentiodynamic polarization study shows that the neem-assisted deposition decreases the degradation rate, with the lowest degradation rate of 0.027 mm/yr for the ZHN2 sample. In addition, the biomineralization process shows the apatite formation on the deposited coating after 21 days of immersion. In vitro cytotoxicity assay exhibits the maximum cell viability of 117% for neem-assisted coated alloy in 30% extract after 5d and the improved cytocompatibility which is due to the controlled release of Zn2+ ions. Meanwhile, neem-assisted coated alloy increases the ZOI by 32 and 24% for Gram-positive and Gram-negative bacteria, respectively. Acceptable hemolysis (<5%) and anticoagulation parameters demonstrate a promising hemocompatibility of the coated alloy. In vivo implantation illustrates a slight inflammatory response and vascularization after 2 weeks of subcutaneous implantation, and neo-bone formation in the defect areas of the rat femur. Micro-CT and histology studies demonstrate better osseointegration with satisfactory biosafety response for the neem-assisted coated alloy as compared to that without neem-assisted deposition. Hence, this neem-assisted brushite-Hap coating strategy elucidates a new perspective on the surface modification of biodegradable implants for the treatment of bone defects.

Development of Zn-2Cu-xMn/Mg Alloys for Orthopedic Applications: Mechanical Performance to In Vitro Degradation under Different Physiological Environments.

Zinc (Zn) and its alloys are considered futuristic biodegradable materials for their acceptable mechanical properties, suitable corrosion rate, and good biocompatibility. In this study, we report newly developed biodegradable Zn-2Cu-xMn/Mg (x = 0, 0.1, and 0.5) alloys, aiming to achieve good mechanical strength with excellent elongation, desirable wear resistance, and suitable corrosion rate. The effect of Mn/Mg addition on the structural, mechanical, wear, and degradation behaviors of the Zn-2Cu-xMn/Mg alloys was thoroughly investigated. Degradation and tribological behaviors of the alloys were explored in the presence of simulated body fluid (SBF), Dulbecco's modified Eagle medium (DMEM), and DMEM with a 10% fetal bovine serum (FBS) solution. Alloy elements and hot rolling improve their mechanical properties significantly due to precipitation hardening, grain refinement, and solid solution strengthening owing to the formation of MnZn13 and Mg2Zn11 phases. Among all the alloys, the Zn-2Cu-0.5Mn alloy achieved the highest ultimate tensile strength (UTS) of ∼405 MPa and yield strength (YS) of ∼293 MPa with an excellent elongation of ∼51%. The corrosion behavior of the alloys as determined by a potentiodynamic polarization study under different solutions follows the sequence Zn-2Cu < Zn-2Cu-0.5Mn < Zn-2Cu-0.1Mn < Zn-2Cu-0.1Mg < Zn-2Cu-0.5Mg. The corrosion rate by immersion testing for 30 and 90 days also follows the same sequence. The corrosion rate in different solutions follows the order SBF > DMEM + 10%FBS > DMEM. The addition of Mn/Mg also improves the wear resistance and slows the wear rate under wet conditions. The bending test results also indicate the highest bending strength of ∼375 MPa for the Zn-2Cu-0.5Mn alloy, among all the alloys. The bending and tensile strengths deteriorate continuously after the immersion for 30 and 90 days in the solution of SBF, DMEM, and DMEM + 10%FBS. Therefore, the Zn-2Cu-xMn/Mg (x = 0.1 and 0.5) alloys can be considered potential biodegradable implant materials.

Influence of Copper on the Microstructural, Mechanical, and Biological Properties of Commercially Pure Zn-Based Alloys for a Potential Biodegradable Implant.

Three Zn-based alloys (Zn1Cu, Zn2Cu, and Zn3Cu) were developed by the addition of Cu (1, 2, and 3 wt %) into commercially pure Zn. This report systematically investigates the potential for these newly developed Zn-based alloys as biodegradable materials. Microstructural studies reveal the presence of spherical-shaped nanosized precipitates of ε-CuZn4 in the Zn1Cu alloy, whereas Zn2Cu and Zn3Cu alloys exhibit the presence of both micron- and nanosized precipitates of ε-CuZn4. The mechanical properties such as hardness, tensile and compressive strengths improve significantly with an increase in the amount of Cu in the alloy. The Zn3Cu alloy exhibits the highest yield strength (225 ± 9 MPa) and ultimate tensile strength (330 ± 12 MPa) among all of the alloys, which are ∼2.7 and 2 times higher than those of pure Zn. In vitro degradation behavior is evaluated by the potentiodynamic polarization study and immersion testing in Hank's solution for 20 and 75 days. The corrosion rate after both polarization and immersion testing follows the order of pure Zn < Zn1Cu < Zn3Cu < Zn2Cu. An electrochemical impedance spectroscopy (EIS) study also concludes that Zn2Cu shows the lowest corrosion resistance. The % cell viability values of 3T3 fibroblasts cells after 5 days of culture in a 50% diluted extract of pure Zn, Zn2Cu, and Zn3Cu alloys are 76 ± 0.024, 86.18 ± 0.033, and 92.9 ± 0.026%, respectively, establishing the improved cytocompatibility of the alloys as compared to pure Zn. Furthermore, an antibacterial study also reveals that the Zn3Cu alloy exhibits 80, 67, and 100% increases in the zone of inhibition (ZOI) for Escherichia coli, Bacillus subtilis, and Pseudomonas aeruginosa bacteria, respectively, as compared to that of pure Zn.