New biodegradable zinc-based materials for biomedical applications
Creators: name: Kabir, Humayun
Publisher: name: RMIT University
Year: 2024
Subjects: classificationCode: 400302
subject: Biomaterials
classificationCode: 401602
subject: Composite and hybrid materials

description: Biodegradable metals (BMs) have attracted considerable attention in clinical applications due to their suitability for use as temporary bone implants and cardiovascular stents. Magnesium (Mg) and iron (Fe) based BMs were the most widely investigated BMs because of their excellent biocompatibility and mechanical properties. Nevertheless, these BMs possess some limitations. Recently, zinc (Zn)-based BMs have drawn scientific attention as alternative BMs owing to their suitable degradation rate compared to Mg- and Fe-based BMs, acceptable cytocompatibility, and excellent antibacterial properties. 
However, the as-cast pure Zn exhibits low mechanical properties, and do not meet the mechanical property requirements for designing implants, which restrict their wide range of biomedical applications. 

The graphene nanoplatelet (GNP) contains a single atomic layer of sp2 carbon atoms with a honeycomb lattice structure, which can provide strong interfacial bonding with matrices, leading to different strengthening mechanisms in enhancing the mechanical strength of metal matrix composites (MMCs). Moreover, GNP exhibits biocompatibility in contact with blood and its large specific surface areas (~ 2630 m2/g) also aid their degradation. However, producing a uniform dispersion of GNP in the Zn matrix is a great challenge. Also, the optimal concentration of GNP in Zn matrix and the fabrication processing of GNP-reinforced Zn matrix composites (ZMCs) are still not fully understood.
 
Meanwhile, pure Zn alloying with suitable alloy elements and usage of appropriate fabrication technique is another functional way to improve mechanical properties of Zn alloys. The addition of rate earth (RE) elements and usage of hot rolling on as-cast (AC) Zn-alloys has recently found very effective to increase the mechanical and biological properties of Zn alloys.

In this research, GNP-reinforced ZMCs (Zn-xGNP; x = 0.1-0.4 wt.%) and Zn-yMg-0.2GNP (y = 0.5, 1.0, 1.5, and 2.0 wt.%) composites were fabricated using powder metallurgy and the morphology, dispersion, and defects of GNP in the ball milled powder mixtures (BMPMs) of Zn-xGNP and Zn-yMg-0.2GNP were evaluated. Their microstructures, mechanical, corrosion, and biocompatibility properties were investigated systematically. The Zn-3Cu-0.4Li (ZCL) and ZCL-zSc (z = 0.20, 0.35, and 0.55 wt.%) alloys were also fabricated using casting followed by hot rolling, and their microstructures, mechanical, corrosion and biocompatibility properties were studied.
  
Firstly, critical milling parameters of high energy ball milling such as specific ball milling energy (SBME) were optimized using 0.2 wt.% of GNP in the pure Zn matrix, and the morphology, dispersion, and defects of GNP in the Zn-0.2GNP BMPMs were evaluated (Chapter 4). The mechanical properties, micro and nano hardness, corrosion properties of the sintered composites were also determined to set up a co-relation between the dispersion processing parameters and the final microstructure of ZMC-0.2GNP. The microhardness (MH), compressive yield strength (σCYS), ultimate compressive strength (σUCS), compressive strain (εF), nano-hardness, and reduced elastic modulus of the ZMC-0.2GNP prepared with optimum SBME (32.82 kJ/g) were 68.7 HV, 123 MPa, 247 MPa, 22.9 %, 1.65 GPa, and 89.04 GPa, respectively, improvements of 66 %, ~ 160 %, ~ 201 %, ~ 51 %, ~ 12 %, and ~26 % compared to the reference sample ball milled at 0.91 kJ/g SBME.
 
Secondly, GNP-reinforced ZMCs by varying GNP contents (0.1-0.4 wt.%) at optimum SBME were fabricated and their microstructure, phase analysis, microhardness, and compressive mechanical properties with strengthening mechanisms, corrosion behavior and biocompatibility properties were investigated (Chapter 5). The MH, σCYS, σUCS, and εF of the ZMC-0.2GNP composites at SBME of 32.82 kJ/g were 69 HV, 123 MPa, 247 MPa, and 23 %, respectively, showing improvements of ~ 18 %, 50%, ~ 28%, and ~ 15% compared to pure Zn, which was due to the synergetic strengthening mechanisms including load-transfer and grain-refinement strengthening. The corrosion rate of the ZMCs were lower than that of the pure Zn in the Hank’s balanced salt solution (HBSS), and the ZMC-0.2GNP exhibited the lowest corrosion rate of 0.09 mm/y. The diluted extracts of ZMC-0.2 GNP revealed more than 90% cell viability after cell culturing of 3 days, showing the satisfying cytocompatibility.

Thirdly, a hot-pressed sintering method was attempted to synthesis Zn-yMg-0.2GNP composites and their mechanical, corrosion, and biocompatibility properties were evaluated (Chapter 6). The addition of Mg to the Zn matrix led to the formation of Mg2Zn11 and MgZn2 phases without any intermetallic carbide phases. The hot-pressing sintered (HPS) Zn–0.5Mg–0.2GNP composite exhibited the best mechanical properties including a σCYS of 168.5 MPa, an σUCS of 270.3 MPa, a εF of 17.1%, and a MH of 85.5 HV. With increase of Mg content, both the corrosion and degradation rates (DRs) of the HPS Zn–yMg–0.2GNP composites successively raised in the HBSS. The extract of both HPS Zn–0.2GNP and Zn–yMg–0.2GNP composites at a concentration of 12.5% after cell culturing for up to 5 d showed more than 100% cell viability in relation to SaOS2 cells, showing excellent cytocompatibility.

Fourthly, biodegradable ZCL and ZCL-zSc alloys were fabricated by casting and further hot-rolled (HR) to improve their mechanical properties (Chapter 7). The microstructures of the HR ZCL mainly contained the η-Zn matrix, β-LiZn4 phase, and rod-like or granular eutectic ε-CuZn5 phase distributed within the Zn matrix. The addition of Sc into ZCL-zSc alloys, an additional stripe-like ScZn12 phase were formed in the ZCL-zSc alloy. With increases in Sc content, the yield strength of the HR alloys increased first and then decreased. The HR ZCL-0.20Sc alloy exhibited the best combined mechanical properties, with a tensile yield strength of 277 MPa, an ultimate tensile strength of 337 MPa, and an elongation of 40%. The DR of the HR ZCL-zSc alloys reduced with increasing immersion time, while it increased with increasing Sc addition. The HR ZCL-0.55Sc alloy displayed the highest degradation rate of 50.1 and 26.9 µm/y measured by immersion testing after 30 d and 60 d immersion in HBSS, respectively. The 50% concentration extracts of the HR ZCL and ZCL-zSc alloys showed no significant toxicity toward human osteoblast-like SaOS2 cells after cell culturing for up to 5 d and their diluted extracts showed more than 100% cell viability after culturing for 1 d, showing outstanding cytocompatibility.

In conclusion, GNP-reinforced ZMC has potential in designing biodegradable bone-implant, however, more research is required to attain their best properties. Overall, the HR ZCL-0.20Sc alloy has great potential as a biodegradable bone-implant material due to its excellent combination of mechanical properties, satisfactory DR, and good biocompatibility.
 
However, intensive in vivo study is required to evaluate their biosafety before bringing them into clinical application.