Biodegredable metals for bone regeneration

BIODEGRADABLE METALLIC MATERIALS FOR
BONE REGENERATION APPLICATIONS
Mohamed Mahmoud Abdul-Monem
Spring 2019
09708
1

INTRODUCTION
 Scaffolds have been utilized in tissue regeneration
to facilitate the formation and maturation of new
tissues or organs where a balance between
temporary mechanical support and degradation and
cell growth is ideally achieved.
 Polymers have been widely chosen as tissue
scaffolding material having a good combination of
biodegradability, biocompatibility, and porous
structure.
3

INTRODUCTION
 Metals that can degrade in physiological
environment, namely, biodegradable metals, are
proposed as potential materials for hard tissue
scaffolding where biodegradable polymers are
often considered as having poor mechanical
properties.
 Biodegradable metal scaffolds have showed
interesting mechanical property that was close to
that of human bone with tailored degradation
behaviour.
4

REQUIREMENTS OF SCAFFOLDS
 Ideally, a scaffold must be porous, bioactive,
and biodegradable and possess adequate
mechanical properties suited to the
biological site.
 Sufficient porosity is needed to
accommodate cell proliferation and
differentiation and for nutrients and
metabolites exchange. 5

 A bioactive scaffold promotes cell-
biomaterial interactions, cell proliferation,
adhesion growth, migration, and
differentiation.
6

 A biodegradable scaffold allows the
replacement of biological tissues via
physiological extracellular components
without leaving toxic degradation products.
 Its degradation rate should match the rate
of new tissue regeneration
7

Mechanically, the major challenge is to
achieve adequate initial strength and
stiffness and to maintain them during the
stage of healing or new tissues generation
throughout the scaffold degradation
process.
8

BIODEGRADABLE METALS (BM)
 There is a recent and fast-growing interest
in the use of biodegradable metals for
biomedical applications
 The inherent strength and ductility owned by
metals are the key features that make them
appealing for hard tissue applications.
10

DEFINITION OF BIODEGRADABLE METALS
 BMs are metals expected to corrode gradually
(Biocorrosion) in vivo, with an appropriate host
response elicited by released corrosion products,
then dissolve completely upon fulfilling the
mission to assist with tissue healing with no implant
residues .
 Thee major component of BM should be essential
metallic elements that can be metabolized by the
human body, and demonstrate appropriate
degradation rates and modes in the human body.
11

CLASSIFICATION OF METALLIC ELEMENTS IN
THE HUMAN BODY.
13

TYPES OF BIODEGRADABLE METALS FOR
BONE REGENERATION
1. Magnesium-based
2. Iron-based
3. Zinc-based
14

TYPES OF BIODEGREDABLE METALLIC ALLOYS
Magnesium
based
Iron-based Zinc-based
Mg-Al Fe-Mn Zn-Mg
Mg-Ca Fe-Al Zn-Ca
Mg-Zn Fe-Ag Zn-Cu
Mg-Sr Fe-Mn-C
Mg-Ag
15

MAGNESIUM- BASED SCAFFOLDS
 Mg is largely found in bone tissue, it is an
essential element to human body, and its
presence is beneficial to bone growth and
strength.
 It is a cofactor for many enzymes and
serves as stabilizer of DNA and RNA
structures.
 With approximately half of the total
estimated 25 g content stored in bone
tissue(12.5g), Mg is the fourth most
abundant cation in the human body.
16

 Mg can be considered as osteoconductive
and bone growth stimulator material.
 Witte et al. (2007) observed that 3 months
postoperatively, porous Mg scaffolds
implanted in rabbits were largely degraded,
foreign body giant cells phagocytizing the
remaining corrosion products were rarely
found, and no osteolytic changes were
found around the implant site. 17

 Mg and its alloys are very lightweight metals
having density ranging from 1.74 to 2.0
g/cm3 which is less than that of Ti alloys
(4.4–4.5 g/cm3) and is close to that of bone
(1.8–2.1 g/cm3)
18

MECHANICAL PROPERTIES OF MAGNESIUM
SCAFFOLDS
 They have a wide range of elongation and
tensile strength from 3% to 21.8% and
from 86.8 to 280 MPa, respectively.
 Mg possess a greater fracture toughness
compared to that of ceramic biomaterials,
and its elastic modulus (41–45 GPa) is
closer to that of the bone compared to other
metals. This property could play a vital
role in avoiding the stress shielding
effect.
19

 Unfortunately, pure Mg corrodes very
quickly in physiological solution.
 Addition of alloying elements such as
aluminium, silver, indium, silicon, tin, zinc,
and zirconium could improve both the
strength and degradation rate of Mg.
21

DEGRADATION OF MAGNESIUM -BASED
SCAFFOLDS
22
•In the first reaction,
gray Mg(OH)2 film is
developed on the
surface of Mg as it
reacts with water and
hydrogen bubbles are
also produced(1).
• The metal can also
directly react with
chloride ions to form Mg
chloride (2).
•This highly soluble
MgCl2 is also formed
through the reaction of
Mg(OH)2
with chloride ions, as
depicted in (3)

DEGRADATION OF MAGNESIUM SCAFFOLDS
23

SURFACE MODIFICATION OF MAGNESIUM
ALLOYS
 In order to efficiently improve the corrosion
resistance of Mg alloys in physiological
environments, as well as maintain their mechanical
integrity and enhance interfacial biocompatibility,
various surface modifications have been
developed.
 Distinct from alloying techniques, surface
modifications directly insulate Mg alloys from the
surrounding biological environment and prevent the
penetration of body fluid into substrates .
24

SURFACE MODIFICATION OF MAGNESIUM
SCAFFOLDS
Chemical
modification
Acid
etching
Alkaline
heat
treatment
Fluoride
treatment
Physical
modification
Apatite
coatings
Polymer
coatings
25

CHEMICAL MODIFICATION
 Acid etching with 2.5% H2SO4 is a pretreatment
method commonly used to remove the coarse scale
produced during manufacturing and replace the
native oxide layer with a more compact passivated
layer .
 Alkali heat treatment with NaOH at160 ˚C, a
simple and economical method, creates a
Mg(OH)2 barrier layer on substrate surface that
slows down the corrosion rate of Mg alloy .
26

CHEMICAL MODIFICATION
 Fluoride treatment of Mg alloys replaces the
original oxide film with a thin and more
homogeneous MgF2 layer with higher polarization
resistance. The advantages of the MgF2 layer
include a high density, low water solubility, and
nontoxicity when fluorine ions are released into the
host organism.
 Fluoride can stimulate osteoblast proliferation,
increase new mineral deposition in cancellous
bones, and decrease the solubility of bone tissue
(Fluroapatite)upon incorporation into the bone . 27

PHYSICAL MODIFICATION
 Apatite coatings could improve the degradation
resistance of implants as a protective layer due to
its relatively low solubility and high thermal
stability .
 Polymer coating with semi-crystalline
biodegradable polymers such as polylactic acid
increase the corrosion resistance of Mg based
alloys.
28

IRON -BASED SCAFFOLDS
 Fe is an essential element that plays significant
roles in human body metabolism including :
 Transport, activation, and storage of
molecular oxygen.
 Reduction of ribonucleotides .
 Decomposition of lipid, protein, and DNA
damages
29

 Fe has a higher elastic modulus (211 GPa)
compared to that of Mg (41 GPa) .
 Peuster et al. are among the first who
proposed (Fe) as a biodegradable metal.
30

 Fe was generally viewed as having too slow
degradation for implant applications.
31

DEGRADATION OF IRON BASED SCAFFOLDS
32
In comparison with the
hydrogen evolution
reaction of Mg-based
alloys, the
degradation of Fe-
based alloys can be
characterized by
oxygen absorption
corrosion in an
aqueous environment

DEGRADATION OF IRON-BASED SCAFFOLDS
33

ZINC–BASED SCAFFOLDS
 Zn is the second most abundant
micronutrient in living organisms and is
fundamental to cell biology, human
anatomy, and physiology.
 Zn deficiency can be observed in growth
failure, but Zn toxicity is rarely a concern as
ingestion of ten times the recommended
daily dose leads to few symptoms.
34

 Zn is required for bone formation and
mineralization, stimulating osteoblasts
while inhibiting bone resorbing osteoclasts.
35

 The Zn2+ ions released from Zn-based
scaffolds materials could potentially interact
with bacterial surfaces, altering charge
balance and inducing cell deformation and
bacteriolysis.
 Theoretically, all Zn-based biodegradable
materials can potentially have antibacterial
abilities. 36

DEGRADATION OF ZINC BASED SCAFFOLDS
37
•The degradation products mainly include Zn-
based compounds, including ZnO, Zn(OH)2,
Zn3(PO4)2 .
• In addition, Ca2+ from body fluids could react
with zinc phosphate and precipitate as calcium
phosphate or Zn-doped calcium phosphate

ADVANTAGES OF BIODEGREADABLE METALS
Magnesium based Iron Based Zinc based
Osteoconductive High
Mechanical
properties
Non-Toxic
degradation
products
Osteoinductive •Stimulate
osteoblasts
• Inhibit
osteoclasts
Light in weight Antibacterial 38

DISADVANTAGES OF BIODEGRADABLE METALS
Magnesium based Iron Based Zinc based
Fast corrosion rate
(1-4 months) which
leads to Premature
loss of mechanical
integrity
Accumulation of
corrosion products
that repel neighboring
cells
Low mechanical
properties
Hydrogen gas
evolution which leads
to gas embolism
Slow degradation
rate (2-3 yrs)
Slow degradation
rate which leads to
fibrous encapsulation
39

40
Degradation rate :
Mg>Zn>Fe

FABRICATION TECHNIQUES OF
BIODEGREDABLE METALLIC SCAFFOLDS
1. Solid free form (3D printing +Casting)
2. 3D printing (Selective laser melting (SLM)
41

1.SOLID FREE FORM BIODEGREDABLE
METALLIC SCAFFOLDS
42
1. Creating a 3D model
with the desired
architecture
usingCAD;
2. Printing a positive
polymeric template of
the model by 3D
printer;
3. Infiltrating the
polymeric template
with a NaCl paste;

4. Removing the template by heating
followed by sintering of NaCl;
5. Casting liquid Mg into NaCl template,
that is, with pressure assistance;
6. Removing NaCl template by dissolution
43

SOLID FREE FORM BIODEGREDABLE
METALLIC SCAFFOLD
44

2.SELECTIVE LASER MELTING (SLM)
Is a rapid prototyping, 3D printing, or additive
manufacturing technique designed to use a high
power-density laser to melt and fuse metallic
powders together.
45

SELECTIVE LASER MELTING (SLM) VIDEO
46

KEY PROPERTIES FOR MATERIAL DESIGN WHEN
CHOOSING BIODEGREDABLE METALS
47

REFERENCES
1. Y.F. Zheng ,X.N. Gu ,F. Witte .Biodegradable
metals ..Materials Science and Engineering R 77
(2014) 1–34 .
2. E Aghion. Biodegradable Metals.Metals.2018;1-4.
3. C.Shuai et al. Biodegradable metallic bone
implants. Mater. Chem. Front., 2019, 3, 544—562.
4. Y.Li.Additively manufactured biodegradable
porousmagnesium.Acta Biomaterialia.2017;500-
520.
48

REFERENCES
5. Y.Liu et al.Fundamental Theory of Biodegradable
Metals—Definition,Criteria, and Design. Adv.
Funct. Mater. 2019;1-21
6. Y.Su et al.Zinc-Based Biomaterials for
Regeneration and Therapy. Trends in
Biotechnology.2019:429-445.
7. A.Yusop et al.Porous BiodegradableMetals for
Hard Tissue Scaffolds: A Review.Int J
Biomat.2012;1-11
8. R.Gorejova et al. Recent advancements in Fe-
based biodegradable materials for bone repair.J
Mat sci .2018:1-35 49

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