MRS Advances © 2018 Materials Research Society

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DOI: 10.1557/adv.2018.488

Magnesium-based Biodegradable Materials for

Biomedical Applications

Chaoxing Zhang1, Jiajia Lin1, Huinan Liu1,2,3,4,*

1Materials Science and Engineering Program, University of California at Riverside, 900 University

Avenue, Riverside, CA 92521, United States

2Department of Bioengineering, University of California at Riverside, 900 University Avenue, Riverside,

CA 92521, United States

3Biomedical Sciences Program, School of Medicine, University of California at Riverside, 900 University

Avenue, Riverside, CA 92521, United States

4Stem Cell Center, University of California at Riverside, 900 University Avenue, Riverside, CA 92521,

USA

ABSTRACT

Magnesium (Mg)-based biomaterials have attracted increasing attention in biomedical

applications, such as orthopaedic, cardiovascular, urological, and neural applications
because of the biocompatibility, biodegradability, antibacterial properties, and excellent
mechanical properties. However, rapid degradation of Mg is the major concern for many
clinical applications. Alloying Mg with other elements and engineering proper surfaces are
the two approaches to control the degradation of Mg-based biomaterials. Our lab has
investigated several classes of Mg-based biodegradable alloys and various surface
treatment methods for medical implant and device applications. This mini-review
highlights key research progress on Mg-based biomaterials and suggests future directions
for Mg-based biomaterials.

INTRODUCTION
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Magnesium (Mg)-based biomaterials provide attractive properties for

biomedical applications, such as orthopaedic [1, 2], cardiovascular [3], urological
[4] and neural applications [5, 6]. In the human body, Mg reacts with water and
naturally degrades, which eliminates the necessity of a secondary removal
procedure for an implant [7]. The degradation products of Mg, i.e. Mg2+ ions, could
activate or catalyse over 300 kinds of enzymes and are needed for many metabolic
processes in the human body [3]. For orthopaedic device applications, Mg2+ ions
could promote bone growth by accelerating the adhesion of bone cells to apatite [8].
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Moreover, the density and mechanical properties of Mg are closer to those of

cortical bone [9], which could reduce the stress-shielding associated issues and
improve bone healing [10]. Excellent biodegradability, biocompatibility and
mechanical properties also make Mg a good candidate material for cardiovascular
stents. Furthermore, Mg alloys showed attractive antimicrobial properties for
ureteral stent application [4]. Lastly, Mg could be used as an electrode material for
neural recording and stimulation applications because of its conductivity and
neuro-protective effect of Mg2+ ions [5].
However, the application of Mg-based materials as biomedical implants is
limited by their corrosion behaviour [11-13]. The rapid degradation of Mg causes
local pH increase and H2 release in a short time after implantation and possible
premature mechanical failure of the implants [14]. Thus, it is critical to improve the
degradation behaviour of Mg-based materials for their potential biomedical
applications [15, 16]. Generally, there are two ways to achieve the goal: (1) alloying
and processing [17]; (2) surface treatments or coatings [7, 14, 18, 19]. Our lab has
investigated various Mg-based biodegradable alloys (e.g., Mg-Y [4, 10, 20-22], Mg-
Zn-Ca-Zr [23], Mg-Zn-Ca [1], Mg-Zn-Sr [8, 9, 24-27], Mg-Sr [17, 28] and Mg-Ca-Sr
[29]) and different surface treatment methods for medical applications [1, 3-10, 14,
17-27, 29-34]. This mini-review highlights our key research progress on Mg-based
biodegradable materials and discusses new directions for the future.

DEVELOPMENT OF MG-BASED ALLOYS

Selecting suitable alloying elements to enhance corrosion resistance and

mechanical properties is critical to consider in the compositional design of Mg-
based alloys. Different elements and composition play different roles on the
mechanical and physical properties because of the changes in the alloy
microstructure and phase distribution. For example, we added yttrium (Y), zinc
(Zn), calcium (Ca), strontium (Sr), and zirconium (Zr) into Mg to form Mg-Y [4, 10,
20-22], Mg-Zn-Ca-Zr [23], Mg-Zn-Ca [1], Mg-Zn-Sr [8, 9, 24-27], Mg-Sr [17, 28] and
Mg-Ca-Sr [29] alloys and investigated their degradation and biocompatibility.

Mg-Y alloys

Y could reduce Mg grain size and increase strength, ductility and

degradation resistance [5, 21]. Mg-Y (4 wt%) alloys were studied for different
medical applications. We first investigated the effects of surface condition and
immersion solution on the degradation of Mg-Y and pure Mg controls in vitro [10].
Specifically, in phosphate buffered saline (PBS), the Mg-Y alloy with metallic surface
degraded the slowest, followed by pure Mg with metallic or oxide surfaces, and the Mg-Y
alloy with oxide surface degraded the fastest. However, in deionized (DI) water, the Mg-
Y alloy with metallic surface degraded the fastest. The results presented the key
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factors to consider when designing new biodegradable Mg implants, such as the

alloy composition, presence or absence of surface oxide layer, and presence or
absence of physiological salt ions. Our following study found that protein was
another major contributing factor to Mg alloy degradation [21]. Proteins had
significant interactions with Mg-based biodegradable metals, and the role of
proteins in the degradation of Mg-based materials may be affected by alloy
composition and processing. Our study on Mg-Y(4 wt%) degradation in culture with
bone marrow derived mesenchymal stem cells (BMSCs) confirmed all these [20].
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The polished Mg-Y alloys showed slower degradation rate and more BMSCs
adhesion than the alloys with oxidized surface in Dulbecco’s Modified Eagle Medium
(DMEM) supplemented with 10% fetal bovine serum (FBS) and 1%
penicillin/streptomycin (P/S) under standard cell culture conditions due to more
stable degradation layer. The degradation behaviour of Mg-Y alloys in the
BMSC/DMEM culture system was different when compared with that in DI water
and PBS system because of the presence of physiological salt ions, proteins, and
cells. Combining the degradation and antibacterial properties, Mg-Y alloys showed
great potential for next-generation ureteral stents applications [4].

Mg-Zn-Ca alloys

Even Y could improve corrosion resistance and/or mechanical strength of

Mg, it still raises concerns on biocompatibility in some cases. Therefore, the
development of new type of Mg-based alloys with nutrient elements that are
naturally present in the human body, such as zinc (Zn) and calcium (Ca), has
attracted increasing interest for biomedical applications. The addition of Zn could
reduce grain size, improve tensile strength and enhance the corrosion resistance of
Mg alloys. Furthermore, Zn is involved in over 300 enzymatic processes in human
body [1]. Ca is a major component of bone. We investigated Mg–xZn–0.5 wt% Ca (x
= 0.5, 1.0, 2.0, 4.0 wt%) alloys and BMSCs response in direct culture [18]. High
BMSCs adhesion density on these alloys that was similar to the cell-only control
group, indicating excellent cytocompatibility of Mg-Zn-Ca alloys with BMSCs and
their promise for orthopaedic applications.

Mg-Zn-Sr alloys

The Mg–Zn alloys could be further alloyed by adding the third alloying
elements, like Sr. The introduction of Sr could refine the microstructures of the Mg–
Zn alloy. We have developed and systematically investigated a new group of
biodegradable Mg–Zn–Sr alloys for biomedical applications. The mechanical
properties of the ZSr41 alloy (4 wt% Zn and ≤1 wt% Sr) were superior as compared
with those of pure Mg, and met the requirements for load-bearing medical implants
[9]. The degradation properties of the ZSr41 alloys and their cytocompatibility were
further studied [24] using a human embryonic stem cells (hESCs) model in vitro.
The results indicated that the ZSr41 alloy with 0.15 wt% Sr exhibited slower
degradation and improved cytocompatibility as compared with pure Mg control.
Furthermore, when the degradation of ZSr41 alloys in blood and their
thrombogenicity for cardiovascular applications were investigated [25], the results
suggested that the ZSr41 alloys degraded faster in platelet rich plasma (PRP) than in
whole blood. The ZSr41 alloy with 4 wt % Zn and 0.15 wt % Sr was identified as the
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most promising alloy for cardiovascular applications due to slower degradation and
less thrombogenicity among four Mg-4 wt% Zn-xSr (x=0.15, 0.5, 1, and 1.5 wt%)
alloys. The potential of ZSr41 alloys for vascular device applications and
orthopaedic applications was confirmed by another two studies [8, 27], which
showed that ZSr41 alloys had good cytocompatibility with human umbilical vein
endothelial cells (HUVECs) and BMSCs in vitro. Finally, the degradation behaviour
and biological properties of ZSr41 alloys for bone repair in vivo were studied [26].
Despite of rapid degradation with a complete resorption time of 8 weeks in the
intramedullary space of rat tibia in vivo, the ZSr41 intramedullary pins induced a
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significant net bone growth. Thus, it is still necessary to further optimize the surface
conditions of Mg-based materials to reduce the degradation rate for biomedical
implant applications.

SURFACE MODIFICATIONS OF MG-BASED BIODEGRADABLE METALS FOR

BIOMEDICAL APPLICATIONS

Anodization

Anodization, also called electrochemical anodic oxidation, was used to

produce adherent protective oxide layers on metals and has shown great potential in
fabricating passivation layers on metal implants such as aluminium [35], titanium [36],
niobium [37] and Mg [19]. Surface characteristics, thickness of the anodic passivation
layer can be adjusted by the type of electrolyte, electrolyte concentration, and applied
current density [38]. Our previous study on the anodization of Mg with different applied
voltages in KOH followed by annealing process showed that homogeneous
nanostructured MgO layer was anodized on the Mg substrates [19]. The anodized Mg
was cytocompatible with BMSCs in vitro, and was found to have reduced H2 gas
formation in physiological solution [19], which should be further explored in vivo for
implants applications.

Biodegradable ceramic coatings

Calcium phosphates are a group of biodegradable ceramics that have been

widely used for orthopaedic applications for many years because calcium-
containing inorganic crystals are naturally found in bone [39]. One of the most
widely used calcium phosphates is hydroxyapatite (HA), which has excellent
biocompatibility, slow biodegradability, and good osteoconductive and
osteoinductive capabilities [39]. Therefore, HA is a desirable coating material on Mg
substrates to combine the cytocompatibility properties of HA with the mechanical
properties of Mg, while serving as a protective layer to decrease Mg degradation.
We have fabricated HA coating on the Mg alloys using electrodeposition [23]. The
HA-coated Mg showed a higher growth rate of fibroblasts than the non-coated Mg,
which provided evidence of acceptable cytocompatibility for biomedical
applications. Nanostructured HA (nHA) coatings were deposited on Mg using the
patented transonic particle acceleration process (patented by N2 Biomedical,
formerly known as Spire Biomedical) to further evaluate the effects of nHA on the
biodegradation and cytocompatibility of Mg implants [33]. The results showed that
nHA coatings decreased Mg degradation and improved BMSC adhesion on the
surface of samples.
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Biodegradable polymer coatings

Polymer-based coatings could provide the protection on the surface of Mg

substrates in the early stage and gradually degrade. We developed four
biodegradable polymer coatings for controlling Mg degradation and HUVECs
adhesion and spreading [3]. Specifically, poly(L-lactic acid) (PLLA), poly(lactic-co-
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glycolic acid) (PLGA) (90:10), PLGA (50:50), and polycaprolactone (PCL) coatings
were deposited on Mg substrates using the spin-coating method and their surface
and biological properties were evaluated. The results showed that the PLGA (50:50)
coating improved the adhesion and spreading of HUVECs the most, which is a
promising coating material for potential cardiovascular applications. For neural
recording and stimulation applications, the conductive polymer, poly(3,4-
ethylenedioxythiophene) (PEDOT), was electrochemically deposited onto Mg
microwires to improve the biodegradability, biocompatibility and biostability of the
electrodes. [5, 6, 32].

Biodegradable composite coatings

Applying polymer/ceramic composites coating on Mg substrate is a new

direction to combine the complementary properties of three type of materials for
biomedical applications. We have investigated biodegradable PLGA/nHA,
PLLA/nHA and PCL/nHA nanocomposites coating on Mg [7, 14], and the results
showed that the melted then annealed PCL/nHA (30 wt% nHA) coating on the
metallic Mg substrates had the slowest degradation and the best coating adhesion
strength, and improved the adhesion density of BMSCs due to reduced internal
stress, water permeability and Mg degradation. Substrate surface conditions,
polymer component types in the nanocomposite coatings and the post-deposition
processing significantly affected the coating adhesion strength at the interface,
sample degradation and BMSC adhesion. This study provided design guidelines for
the nanocomposite coatings on Mg for potential biomedical applications.

CONCLUSIONS

Various Mg-based biodegradable alloys (e.g., Mg-Y [4, 10, 20-22], Mg-Zn-
Ca-Zr [23], Mg-Zn-Ca [1], Mg-Zn-Sr [8, 9, 24-27], Mg-Sr [17, 28] and Mg-Ca-Sr [29])
with proper surface treatments (e.g. anodization, coating with ceramics, polymers
and composites) have been studied for medical implant applications in bone,
vascular, urological, and neural systems. This paper provides a concise overview of
our recent research and progress on Mg-based biomaterials. To further improve the
biological performance of materials in vitro and in vivo for successful clinical
translation, it is necessary to integrate alloy design, processing strategies, and
surface treatment. The ultimate goal of our research on biodegradable metals and
composites is to synergize bifunctionality, biocompatibility, biodegradability,
antibacterial, mechanical, and electrical properties of materials for meeting the
critical clinical needs in specific application.
https://doi.org/10.1557/adv.2018.488

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