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Metallic scaffolds for
bone tissue engineering
Mohamed Mahmoud Abdul-Monem
09-708
Spring 2019
1
Content
• Introduction
• Requirements of metallic scaffolds for bone
tissue engineering
• Types of metallic scaffolds for bone tissue
engineering .
• Fabrication techniques of metallic scaffolds for
bone tissue engineering
• References
2
Introduction
• Bone tissue engineering is an emerging
interdisciplinary field in science, combining
expertise in medicine, material science and
biomechanics.
• Porous scaffolds are essential to hard tissue
engineering strategies because they provide a 3D
framework for delivering cells or regenerative
factors in an organized manner to repair or
regenerate damaged tissues.
3
4
5
Scaffolds for bone
tissue engineering
Polymeric Ceramic Metallic Composites
6
Metallic
scaffolds
Biodegredable
For small-sized
defects
Non-
Biodegredable
For Large-sized
defects
•Mg
•Fe
•Zn
•Ti
•Ni-Ti
•Ta
•St.St
•Co-Cr
Requirements of metallic scaffolds
for bone tissue engineering
• Total porosity
Parameter
• Percentage of
total void
space
Definition
• Affects
mechanical
strength of
the scaffold
Biological
response
7
8
Requirements of metallic scaffolds
for bone tissue engineering
9
• Open
porosity
Parameter
• Percentage of
pores that are
interconnected
Definition
• Affects cell
permeability and
vascularization,
as well as growth
factor diffusion
Biological
response
10
Requirements of metallic scaffolds
for bone tissue engineering
11
• Surface area
to volume
ratio
Parameter
• Ratio of total
scaffold surface
area to total
scaffold volume
Definition
• Cell seeding
density and
concentration
of growth
factors
Biological
response
Requirements of metallic scaffolds
for bone tissue engineering
12
• Pore Diameter
Parameter
• Diameter of
largest sphere
that fits within
pore channel
Definition
• Cell
infiltration
and bone
ingrowth
Biological
response
13
Requirements of metallic scaffolds
for bone tissue engineering
14
• Stiffness
Parameter
• Mechanical
property
Definition
• Affects cell
attachment
Biological
response
Metallic scaffolds
Disadvantage How to overcome ?
1. Lack of biological recognition
on the material surface
(Bioninert)
•Surface coating or surface
modification
•Integrate cell-recognizable
ligands and signaling growth
factors on the surface of the
scaffolds
2.Release of toxic metallic ions
and/or particles through
corrosion
Surface modification
3.High elastic modulus which
leads to stress shielding
Use of composite scaffolds
4. Difficult in processing and
porosity control
Rapid prototyping
15
16
Non –Biodegredable
Metallic scaffolds for bone
tissue engineering
Titanium
alloys
Nickel
Titanium
Tantalum
Stainless
steel
Cobalt
Chromium
I.Titanium alloys scaffolds
Advantages Disadvantages
•Osseointegration •Toxicity from Aluminum and
vanadium
•High Mechanical properties •Susceptible to crack
propagation
•Biocompatible
(Passive oxide layer)
•Low wear resistance compared
to Co-Cr
•Low Density
•Not ferromagnetic
(MRI Compatible)
17
Surface modification of Titanium
scaffolds
• Ti alloys are classified as biocompatible
materials; however, being bioinert materials,
they do not possess the required bioactivity to
bond to bone directly, resulting in a longer
recovery time for bone regeneration.
• Without surface modification ,Ti alloys are
generally encapsulated by soft-fibrous
connective tissue.
18
Surface modification of Ti scaffolds
19
Mechanical
Machining
Grinding
Sandblasting
Physical
Thermal
sprayed
coatings
e.g Plasma arc
spray of
Hydroxyapatite
or Titanium
oxide
Chemical
Acidic
treatment
Alkaline
treatment
Hydrogen
peroxide
Sol-Gel
Anodic
oxidation
Mechanical modification of titanium
scaffolds
20
Physical modification of titanium
scaffolds
21
Chemical modification of titanium
scaffolds
22
II.Nickel Titanium alloys scaffolds
Advantages Disadvantages
•Shape memory •Allergy and Toxicity from
Ni
In order to overcome this
problem:
1. surface modifications
such as oxidation
treatment of NiTi to
obtain a Ni-free surface
2. Ni-free shape memory
alloys, mainly niobium
based, are currently
under development.
•Superelasticity
•Elastic modulus close to
bone
23
III.Tantalum scaffolds
Advantages Disadvantages
•High volume porosity (80%) •Higher coefficient of friction
than bone
•Interconnected pores •High production cost
•Modulus of elasticity similar
to bone
•Difficult processing due to
high melting point (3017˚C)
compared to Ti (1668˚C)
and high oxygen affinity
•Biocompatible due to self-
passivating oxide layer
•High density (16.65 g/cm3 )
compared to Ti(4.5 g/cm3 )
•Corrosion resistant
•Osseointegration
•Excellent cell attachment
24
IV.Stainless steel scaffolds
Advantages Disadvantages
•Corrosion resistance due to
high chromium content (12%)
•Lower Biocompatibility than
Ti alloys due to chromium
and Nickel content in some
alloys .
•Low cost •No osseointegration
25
V.Cobalt Chromium scaffolds
Advantages Disadvantages
•Higher wear resistance
compared to Ti alloys
•Higher modulus of elasticity
than bone which leads to
great stress shielding
•High strength •Low biocompatibility
•High ductility •No osseointegration
26
Comparison between different
metallic scaffolds
27
Elastic modulus of different metallic
scaffolds compared to bone
28
UHMW PE : ultra high molecular weight polyethylene
Fabrication techniques of metallic
scaffolds
I.Conventional techniques
II.Rapid prototyping
29
I.Conventional techniques
1. Sintered metal powder
2. Sintered metal fibers
3. Space-holder method
4. Gas injection into the metal melt
30
However, there are inherent limitations in
these processing methods, which offer little
capability to control precisely pore size, pore
geometry, pore interconnectivity and
spatial distribution of pores.
31
1.Sintered metal powder
32
Sintering
Metal powder Porous metallic
scaffold
2.Sintered metal fiber
33
Sintereing
Metal fibers
Porous metallic
scaffold
Sintering vs melting
34
3.Space holder method
35
4.Gas injection into metal melt
36
II.Rapid prototyping
Rapid prototyping allows fully interconnected
porous network and highly controllable
porosity and pore size.
37
Rapid prototyping includes:
1. Selective laser sintering (SLS)
2. 3D fiber deposition
38
1.Selective laser sintering
39
2.3D fiber deposition
40
41
Porous Tantalum scaffold
42
Defect Ta scaffold in place
43
Push-out test
44
45
a Ta+BMP
b Ta
c Blank
46
47
References
1. Matassi et al.Porous metal for orthopedics implants
Clinical Cases in Mineral and Bone Metabolism 2013;
10(2): 111-115
2. Nouri et al.Biomimetic Porous Titanium Scaffolds for
Orthopedic and Dental Applications.Biomemtics
learning from nature .2010 :416-450
3. Alvarez et al.Metallic scaffolds for bone regeneration.
Materials 2009, 2, 790-832
4. Glenske et al.Applications of Metals for Bone
Regeneration. Int. J. Mol. Sci. 2018:1-32
5. Ahmadi Set al. Mechanical behavior of regular open-cell
porous biomaterials made of diamond lattice unit cells.
Journal of the mechanical behavior of biomedical
materials 2014; 34:106-15.
48
References
6. Hazlehurst Ket al.An investigation into the flexural
characteristics of functionally graded cobalt chrome femoral
stems manufactured using selective laser melting. Materials &
Design 2014; 60:177-83.
7. Wang et al.Application of combined porous tantalum
scaffolds loaded with bone morphogenetic protein 7 to repair
of osteochondral defect in rabbits.Int Orthoped.2018 :1-12
8. Cheng et al.Advances in Porous Scaffold Design for Bone and
Cartilage TissueEngineering and Regeneration.
9. Prasad et al.Metallic Biomaterials: Current Challenges and
Opportunities. Materials 2017:1-33
10. Chen et al.Biocompatible porous titanium scaffolds produced
using a novel spaceholder technique.Society for
biomaterials.2017:2796-2807
11. Wally et al.Porous Titanium for Dental Implant Applications.
Metals 2015;5:1902–1920.
12. Pacifici et al. Metals used in maxillofacial surgery. Oral
Implantol. 2016, 9,107–111.
49
50

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Metallic scaffolds for bone tissue engineering

  • 1. Metallic scaffolds for bone tissue engineering Mohamed Mahmoud Abdul-Monem 09-708 Spring 2019 1
  • 2. Content • Introduction • Requirements of metallic scaffolds for bone tissue engineering • Types of metallic scaffolds for bone tissue engineering . • Fabrication techniques of metallic scaffolds for bone tissue engineering • References 2
  • 3. Introduction • Bone tissue engineering is an emerging interdisciplinary field in science, combining expertise in medicine, material science and biomechanics. • Porous scaffolds are essential to hard tissue engineering strategies because they provide a 3D framework for delivering cells or regenerative factors in an organized manner to repair or regenerate damaged tissues. 3
  • 4. 4
  • 5. 5 Scaffolds for bone tissue engineering Polymeric Ceramic Metallic Composites
  • 7. Requirements of metallic scaffolds for bone tissue engineering • Total porosity Parameter • Percentage of total void space Definition • Affects mechanical strength of the scaffold Biological response 7
  • 8. 8
  • 9. Requirements of metallic scaffolds for bone tissue engineering 9 • Open porosity Parameter • Percentage of pores that are interconnected Definition • Affects cell permeability and vascularization, as well as growth factor diffusion Biological response
  • 10. 10
  • 11. Requirements of metallic scaffolds for bone tissue engineering 11 • Surface area to volume ratio Parameter • Ratio of total scaffold surface area to total scaffold volume Definition • Cell seeding density and concentration of growth factors Biological response
  • 12. Requirements of metallic scaffolds for bone tissue engineering 12 • Pore Diameter Parameter • Diameter of largest sphere that fits within pore channel Definition • Cell infiltration and bone ingrowth Biological response
  • 13. 13
  • 14. Requirements of metallic scaffolds for bone tissue engineering 14 • Stiffness Parameter • Mechanical property Definition • Affects cell attachment Biological response
  • 15. Metallic scaffolds Disadvantage How to overcome ? 1. Lack of biological recognition on the material surface (Bioninert) •Surface coating or surface modification •Integrate cell-recognizable ligands and signaling growth factors on the surface of the scaffolds 2.Release of toxic metallic ions and/or particles through corrosion Surface modification 3.High elastic modulus which leads to stress shielding Use of composite scaffolds 4. Difficult in processing and porosity control Rapid prototyping 15
  • 16. 16 Non –Biodegredable Metallic scaffolds for bone tissue engineering Titanium alloys Nickel Titanium Tantalum Stainless steel Cobalt Chromium
  • 17. I.Titanium alloys scaffolds Advantages Disadvantages •Osseointegration •Toxicity from Aluminum and vanadium •High Mechanical properties •Susceptible to crack propagation •Biocompatible (Passive oxide layer) •Low wear resistance compared to Co-Cr •Low Density •Not ferromagnetic (MRI Compatible) 17
  • 18. Surface modification of Titanium scaffolds • Ti alloys are classified as biocompatible materials; however, being bioinert materials, they do not possess the required bioactivity to bond to bone directly, resulting in a longer recovery time for bone regeneration. • Without surface modification ,Ti alloys are generally encapsulated by soft-fibrous connective tissue. 18
  • 19. Surface modification of Ti scaffolds 19 Mechanical Machining Grinding Sandblasting Physical Thermal sprayed coatings e.g Plasma arc spray of Hydroxyapatite or Titanium oxide Chemical Acidic treatment Alkaline treatment Hydrogen peroxide Sol-Gel Anodic oxidation
  • 20. Mechanical modification of titanium scaffolds 20
  • 21. Physical modification of titanium scaffolds 21
  • 22. Chemical modification of titanium scaffolds 22
  • 23. II.Nickel Titanium alloys scaffolds Advantages Disadvantages •Shape memory •Allergy and Toxicity from Ni In order to overcome this problem: 1. surface modifications such as oxidation treatment of NiTi to obtain a Ni-free surface 2. Ni-free shape memory alloys, mainly niobium based, are currently under development. •Superelasticity •Elastic modulus close to bone 23
  • 24. III.Tantalum scaffolds Advantages Disadvantages •High volume porosity (80%) •Higher coefficient of friction than bone •Interconnected pores •High production cost •Modulus of elasticity similar to bone •Difficult processing due to high melting point (3017˚C) compared to Ti (1668˚C) and high oxygen affinity •Biocompatible due to self- passivating oxide layer •High density (16.65 g/cm3 ) compared to Ti(4.5 g/cm3 ) •Corrosion resistant •Osseointegration •Excellent cell attachment 24
  • 25. IV.Stainless steel scaffolds Advantages Disadvantages •Corrosion resistance due to high chromium content (12%) •Lower Biocompatibility than Ti alloys due to chromium and Nickel content in some alloys . •Low cost •No osseointegration 25
  • 26. V.Cobalt Chromium scaffolds Advantages Disadvantages •Higher wear resistance compared to Ti alloys •Higher modulus of elasticity than bone which leads to great stress shielding •High strength •Low biocompatibility •High ductility •No osseointegration 26
  • 28. Elastic modulus of different metallic scaffolds compared to bone 28 UHMW PE : ultra high molecular weight polyethylene
  • 29. Fabrication techniques of metallic scaffolds I.Conventional techniques II.Rapid prototyping 29
  • 30. I.Conventional techniques 1. Sintered metal powder 2. Sintered metal fibers 3. Space-holder method 4. Gas injection into the metal melt 30
  • 31. However, there are inherent limitations in these processing methods, which offer little capability to control precisely pore size, pore geometry, pore interconnectivity and spatial distribution of pores. 31
  • 32. 1.Sintered metal powder 32 Sintering Metal powder Porous metallic scaffold
  • 33. 2.Sintered metal fiber 33 Sintereing Metal fibers Porous metallic scaffold
  • 36. 4.Gas injection into metal melt 36
  • 37. II.Rapid prototyping Rapid prototyping allows fully interconnected porous network and highly controllable porosity and pore size. 37
  • 38. Rapid prototyping includes: 1. Selective laser sintering (SLS) 2. 3D fiber deposition 38
  • 41. 41
  • 43. Defect Ta scaffold in place 43
  • 46. 46
  • 47. 47
  • 48. References 1. Matassi et al.Porous metal for orthopedics implants Clinical Cases in Mineral and Bone Metabolism 2013; 10(2): 111-115 2. Nouri et al.Biomimetic Porous Titanium Scaffolds for Orthopedic and Dental Applications.Biomemtics learning from nature .2010 :416-450 3. Alvarez et al.Metallic scaffolds for bone regeneration. Materials 2009, 2, 790-832 4. Glenske et al.Applications of Metals for Bone Regeneration. Int. J. Mol. Sci. 2018:1-32 5. Ahmadi Set al. Mechanical behavior of regular open-cell porous biomaterials made of diamond lattice unit cells. Journal of the mechanical behavior of biomedical materials 2014; 34:106-15. 48
  • 49. References 6. Hazlehurst Ket al.An investigation into the flexural characteristics of functionally graded cobalt chrome femoral stems manufactured using selective laser melting. Materials & Design 2014; 60:177-83. 7. Wang et al.Application of combined porous tantalum scaffolds loaded with bone morphogenetic protein 7 to repair of osteochondral defect in rabbits.Int Orthoped.2018 :1-12 8. Cheng et al.Advances in Porous Scaffold Design for Bone and Cartilage TissueEngineering and Regeneration. 9. Prasad et al.Metallic Biomaterials: Current Challenges and Opportunities. Materials 2017:1-33 10. Chen et al.Biocompatible porous titanium scaffolds produced using a novel spaceholder technique.Society for biomaterials.2017:2796-2807 11. Wally et al.Porous Titanium for Dental Implant Applications. Metals 2015;5:1902–1920. 12. Pacifici et al. Metals used in maxillofacial surgery. Oral Implantol. 2016, 9,107–111. 49
  • 50. 50