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BMFB 4713 GREEN MATERIALS AND
BIOMATERIALS
ASSIGNMENT
BIOCERAMICS
Sii Hee Hing B051410093
Sisubalan a/l Selvan B051410128
Marked by: Dr. Zaleha bt. Mustafa
TABLE OF CONTENTS
Page
CHAPTER
1.0 INTRODUCTION
1.1 Classification of biomaterials 1
1.2 Properties of biomaterials 2
1.3 Biocompatibility 3
2.0 BIOCERAMICS BIOMATERIALS
2.1 Types of bioceramics 4
2.1.1 Bioinert bioceramics 5
2.1.2 Bioresorbable ceramic 6
2.1.3 Bioactive ceramics 9
2.2 The pros and cons of the bioceramics 9
3.0 TESTS ON BIOMATERIALS
3.1 In Vitro Test on Bioceramics 11
3.2 In Vivo Test on Bioceramics 13
4.0 CONCLUSION 15
REFERENCES 16
1.0 Introduction
Biomaterials are non-viable materials that can be implanted to replace or repair
missing tissue (Williams, 1987). They may be of natural origin or synthesized in a laboratory.
They can be solid and sometimes liquid which used in medical devices or in contact with
biological systems. Biomaterials as a field has seen steady growth over its approximately half
century of existence and uses ideas from medicine, biology, chemistry, materials science and
engineering. Although biomaterials are primarily used for medical applications, they are also
used to grow cells in culture, to assay for blood proteins in the clinical laboratory, in
processing biomolecules in biotechnology, for fertility regulation implants in cattle, in
diagnostic gene arrays, in the aquaculture of oysters and for investigational cell-silicon
"biochips." The commonality of these applications is the interaction between biological
systems and synthetic or modified natural materials. Biomaterials are rarely used on their
own but are more commonly integrated into devices or implants. Thus, the subject cannot be
explored without also considering biomedical devices and the biological response to them.
1.1 Classification of biomaterials
Biomaterials can be metals, ceramics, polymers, glasses, carbons, and composite
materials. Such materials are used as molded or machined parts, coatings, fibers, films, foams
and fabrics. To put it simple, there are 4 main types of biomaterials that can be found
nowadays;
1. Polymeric biomaterials
2. Metallic biomaterials
3. Bioceramics
4. Biocomposite
1
1.2 Properties of biomaterials
Biomaterials are famous for being inert or biocompatible against the user’s body
immune system. Apart from that, it is also widely used especially in medical application due
to its amazing properties. Furthermore, a biomaterial should not be toxic, unless it is
specifically engineered for such requirements, for example like “smart bomb” drug delivery
system that targets cancer cells and destroys them. The study of toxicity (Toxicology), deals
with methods to evaluate how well this design criterion is met when a new biomaterial is
under development.
Other properties of biomaterials;
1. Non-inflammatory
2. Non-carcinogenic
3. Biofunctional for its lifetime in the host
4. Nonallergic
2
1.3 Biocompatibility
Biocompatibility is the ability of a material to perform with an appropriate host response
in a specific application. Host response is a short term used for the reaction of a living system
to the presence of a material. There are 2 concept of biocompatibility; a) Based on the
biological aspects and, b) based on its mechanical features.
 Biology → Materials that do not create any diverse tissues reaction to host. There are
two types of tests that can be used to test the reaction of the biomaterials to the host;
 In vitro → in an artificial environment outside the living organisms.
 In vivo → in the living organisms.
 Mechanical → Based on this aspect, biomaterials are said to be the materials that have
specific and suitable mechanical properties that can sustained and can be used without
or least failure for a long period. These are some mechanical features that are being
considered in any biomaterials so that it can be used for a long period and also for the
safety purposes.
 Stress-strain behaviour
 Mechanical failure
 Brittle crack failure
3
Figure 1: In vitro (Left), In Vivo (Right)
2.0 Bioceramic
Bioceramic is a term introduced for biomaterials that are produced by sintering or
melting inorganic raw materials to create an amorphous or a crystalline solid body that can be
used as an implant. Bioceramics are typically used as rigid materials in surgical implants,
though some bioceramics are flexible. It is also the class of ceramics that are being used for
repair and replacement of diseased and damaged parts of the musculoskeletal system.
2.1 Types of bioceramics
There are 3 classes of bioceramics
 Nonabsorbable or relatively bioinert bioceramic.
 Bioactive or surface-reactive ceramic.
 Biodegradable or bioresorbable ceramic.
Figure 2: Bioceramics used in biomedical application
4
2.1.1 Nonabsorbable or relatively bioinert bioceramic
These ceramics maintain their physical and mechanical properties while in the host.
They resist corrosion and wear even under high stress and extreme conditions. Relatively
bioinert ceramics are typically used as structural–support implants, for example like bone
plates, bone screws, and femoral heads.
Example of bioinert bioceramic materials;
 Alumina (Al2O3)
It’s also known as Aluminium Oxides. Alumina has a rhombohedral structure.
Alumina commonly been used in orthopaedics fields. It has high hardness at which is
accompanied by low friction and inertness to the in-vivo environment. This property
is one of the reasons why alumina can be used as an ideal material for the joint
replacement.
 Carbons (C)
Carbon is one of the widely used components in biomaterial or medical fields. It can
be made in many allotropic forms like graphite, crystalline diamond, monocrystalline
glassy carbon and quasicrystalline pyrolitic carbon. The crystalline structure of carbon
that being used in implant is similar to the graphite. Since, carbons exhibit good
compatibility with body tissues, these materials have been used extensively for
repairing diseased heart valves and blood vessels.
5
Figure 3: Femoral heads used in total hip replacements
Figure 4: Application of Alumina as bone screws and bone plates
2.1.2 Biodegradable or bioresorbable ceramic
Biodegradable or bioresorbable ceramic degrades upon implantation in the host. This
will be done chemically by the body. The resorbed material will be replaced by endogenous
tissues. The chemicals produced during the degradation must be able to be processed through
the normal metabolic pathways of the body without evoking any deleterious effects. Calcium
phosphates would be one of the most widely used biodegradable ceramics in medical fields
especially in bone replacement. This is because due to its structures which resembles the
bone minerals. There are 7 different forms of calcium phosphate that varies each other in
terms of its Ca/P ratio, water content, pH, impurities and temperature. Calcium phosphates
typically form a family compounds known as “apatites”. Below are some examples of
apatites;
a) Monocalcium phosphate monohydrate(MCPM) → Triclinic structure
b) Dicalcium phophatre dehydrate(DCPC) → Monoclinic structure.
6
Bone PlateBone screw
Figure 5: Scaffold and Dental implant screws
Figure 6: Calcium phosphate being used in bone regeneration
Figure 7: Application of Calcium Phosphates in Dental implants
7
Figure 8: Injectable bone substitutes of hydroxyapatite used for orthopaedic trauma
Figure 9: Calcium Phosphate as filler materials
8
2.1.3 Bioactive or surface-reactive ceramics
These are ceramic or inorganic materials that upon implantation in the host form
string bonds with the adjacent tissues. In simpler terms, bioactive ceramics are able to form
chemical bonds directly to the host biological tissues. Sometime, the bioceramics like
Hydroxyapatite (HA) also called as glass ceramics. This type of bioceramics is commonly
used in replacement of damaged parts or tissue with synthetic or man-made parts or
components. For example like being used in femoral knee or hip replacement.
2.2 The advantages and disadvantages of the bioceramic
Pros Cons
 Biological compatibility and activity  Brittle (low fracture resistance)
 Less stress shielding  Low tensile strength
 High corrosion or wear resistance  Poor fatigue resistance
 High modulus (stiffness) and
compressive strength
 No disease transmission
Table 1: Advantages and disadvantages of bioceramics
9
Figure 10: Hydroxyapatite (HA) used with metallic
biomaterials in hip replacement
3.0 Tests on Biomaterials
There are two types of tests for biomaterials, which are In Vitro testing and In Vivo
testing. These tests are used to determine the biocompatibility and the longevity of the
implants. These tests are also for the purpose of identifying the stability of an implant.
Furthermore, these tests are mandatory in order to avoid any potential harmful effects to the
host during or as it being used.
As shown in figure 11, any newly designed biomaterial should undergo clinical trials.
These biomaterials only can be used after it is screened through a series of in vitro
biocompatibility testing. Once it is found to be non-toxic, it will be recommended for in vivo
osseointegration tests. The in vivo tests essentially involve implanting the material in an
animal model and the evaluation of its histocompatibility. This is followed by clinical trials in
human patients. Both the animal and human trials mandatorily require approval from the
institutional ethics committee.
Figure 11: Steps involved in the translation of newly developed biomaterials from benchside
to bedside. (Greeshma Thrivikramanab, Giridhar Madrasb and Bikramjit Basu)
10
3.1 In Vitro Test on Bioceramics
Figure 12: Schematic illustration showing how nano/submicron particulates can be prepared,
from starting bulk materials to study the toxicity of biomaterial eluates.
11
The generation of wear debris and its accumulation in and around the implant are
inevitable in the case of many prosthetic systems, due to mechanical stresses, as well as the
continuous exposure to body fluids. Since the friction and wear of the implants strongly
depend on the surrounding environment, the exposed surfaces will undergo chemical
dissolution/degradation, either by the body fluids or by the foreign body reaction, elicited by
invading immune cells. Hence to prevent this from happening and to measure the wear rates
that affect the toxicity, in vitro testing will be carried out.
As shown in figure 12, the first step towards the toxicity assessment of ultrafine
particles is to synthesize finer particulates from bulk materials (biomaterials). Once such
particles are prepared, one can prepare an eluate by dissolving such particles in phosphate
buffered saline (PBS) or other medium. Furthermore, Fig. 12 shows the recommended
sequence of various biochemical assays to evaluate the toxicity potential of biomaterial eluate.
12
3.2 In Vivo tests on Bioceramics
Figure 13: Photomicrographs of host bone–implant interface after 14 weeks of implantation showing;
(a) Bonding between bone and implant, without implant loosening/inflammation/implant gap, (b)
Implant interface gap with less bone integration. Red arrow represents the blue stained region
showing signs of inflammation and fibrosis, (c) The steps involved in the sample preparation for
histopathological examination.
13
In order to claim a newly developed material as an ideal implant, it must undergo
extensive investigation (both in vitro and in vivo) to assess the biocompatibility, mechanical
stability and safety. The results from short term in vitro studies can be difficult to extrapolate
to the in vivo situation. Many biological reactions in vivo are rather complex. For this reason,
the use of animal models is an essential step in the testing of orthopedic and dental implants,
prior to clinical use in humans.
In vivo tests allow the implanted material to come into contact with different cell
types and also provide interactions with blood, proteins, enzymes and other hormones.
Despite the availability of numerous animal models for testing the biological performance of
implants, the choice of a suitable model is always crucial, based on the type of study. As the
in vivo assessment of tissue compatibility of a biomaterial is focused on the end-use
application, it must be noted that a biomaterial considered compatible for one application
may not be compatible for another application.
Fig. 13a shows an example of the histopathological structure and morphology of
neobone formation at the interface between a natural bone and a synthetic polymer
biocomposite. At the end of the implantation period of 4 weeks, a bone segment at the
implant site was dissected and processed for histopathological observations (see Fig. 13c).
The implant interface gap due to less bone integration is shown in Fig. 13b. The interfacial
gap induces inflammation and fibrosis, that eventually hinders neo-osteogenesis (Fig. 13b).
14
4.0 Conclusion
In summary, biomaterials are a growing field that focuses on the development of
materials to replace or augment human tissues. Biomaterials play an essential role in medical
field especially in tissue or parts replacement inside the living body. It is inert and famous
for its biocompatibility against the host or the body immune system. Meanwhile, bioceramic
are ceramics that have the properties of biomaterials and can be used medical applications
that won’t cause any side or harmful effects to the host. Bioceramics are typically used as
rigid materials in surgical implants, though some bioceramics are flexible. Nowadays,
bioceramics are widely being used in bone transplants in the form of hydroxyapatite or
calcium phosphate which might saves millions life.
15
References
[1] Biomaterials in orthopaedics (2016, Jan 2)
Retrieved from
https://www.slideshare.net/harivenkat1990/biomaterials-in-orthopaedics-ppt
[2] Bioceramics (2017, August 24)
Retrieved from
https://en.wikipedia.org/wiki/Bioceramic
[3] Biomaterials (2017, August 13)
Retrieved from
https://en.wikipedia.org/wiki/Biomaterial
[4] Biomaterials – an overview (2014, June 26)
Retrieved from
https://www.slideshare.net/manishamanoharan/biomaterials-an-overview
[5] In vitro/In vivo assessment and mechanisms of toxicity of bioceramic materials and its
wear particulates (2014, March 5)
Retrieved from
http://pubs.rsc.org/en/content/articlehtml/2014/ra/c3ra44483j
16

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BIOCERAMICS

  • 1. BMFB 4713 GREEN MATERIALS AND BIOMATERIALS ASSIGNMENT BIOCERAMICS Sii Hee Hing B051410093 Sisubalan a/l Selvan B051410128 Marked by: Dr. Zaleha bt. Mustafa
  • 2. TABLE OF CONTENTS Page CHAPTER 1.0 INTRODUCTION 1.1 Classification of biomaterials 1 1.2 Properties of biomaterials 2 1.3 Biocompatibility 3 2.0 BIOCERAMICS BIOMATERIALS 2.1 Types of bioceramics 4 2.1.1 Bioinert bioceramics 5 2.1.2 Bioresorbable ceramic 6 2.1.3 Bioactive ceramics 9 2.2 The pros and cons of the bioceramics 9 3.0 TESTS ON BIOMATERIALS 3.1 In Vitro Test on Bioceramics 11 3.2 In Vivo Test on Bioceramics 13 4.0 CONCLUSION 15 REFERENCES 16
  • 3. 1.0 Introduction Biomaterials are non-viable materials that can be implanted to replace or repair missing tissue (Williams, 1987). They may be of natural origin or synthesized in a laboratory. They can be solid and sometimes liquid which used in medical devices or in contact with biological systems. Biomaterials as a field has seen steady growth over its approximately half century of existence and uses ideas from medicine, biology, chemistry, materials science and engineering. Although biomaterials are primarily used for medical applications, they are also used to grow cells in culture, to assay for blood proteins in the clinical laboratory, in processing biomolecules in biotechnology, for fertility regulation implants in cattle, in diagnostic gene arrays, in the aquaculture of oysters and for investigational cell-silicon "biochips." The commonality of these applications is the interaction between biological systems and synthetic or modified natural materials. Biomaterials are rarely used on their own but are more commonly integrated into devices or implants. Thus, the subject cannot be explored without also considering biomedical devices and the biological response to them. 1.1 Classification of biomaterials Biomaterials can be metals, ceramics, polymers, glasses, carbons, and composite materials. Such materials are used as molded or machined parts, coatings, fibers, films, foams and fabrics. To put it simple, there are 4 main types of biomaterials that can be found nowadays; 1. Polymeric biomaterials 2. Metallic biomaterials 3. Bioceramics 4. Biocomposite 1
  • 4. 1.2 Properties of biomaterials Biomaterials are famous for being inert or biocompatible against the user’s body immune system. Apart from that, it is also widely used especially in medical application due to its amazing properties. Furthermore, a biomaterial should not be toxic, unless it is specifically engineered for such requirements, for example like “smart bomb” drug delivery system that targets cancer cells and destroys them. The study of toxicity (Toxicology), deals with methods to evaluate how well this design criterion is met when a new biomaterial is under development. Other properties of biomaterials; 1. Non-inflammatory 2. Non-carcinogenic 3. Biofunctional for its lifetime in the host 4. Nonallergic 2
  • 5. 1.3 Biocompatibility Biocompatibility is the ability of a material to perform with an appropriate host response in a specific application. Host response is a short term used for the reaction of a living system to the presence of a material. There are 2 concept of biocompatibility; a) Based on the biological aspects and, b) based on its mechanical features.  Biology → Materials that do not create any diverse tissues reaction to host. There are two types of tests that can be used to test the reaction of the biomaterials to the host;  In vitro → in an artificial environment outside the living organisms.  In vivo → in the living organisms.  Mechanical → Based on this aspect, biomaterials are said to be the materials that have specific and suitable mechanical properties that can sustained and can be used without or least failure for a long period. These are some mechanical features that are being considered in any biomaterials so that it can be used for a long period and also for the safety purposes.  Stress-strain behaviour  Mechanical failure  Brittle crack failure 3 Figure 1: In vitro (Left), In Vivo (Right)
  • 6. 2.0 Bioceramic Bioceramic is a term introduced for biomaterials that are produced by sintering or melting inorganic raw materials to create an amorphous or a crystalline solid body that can be used as an implant. Bioceramics are typically used as rigid materials in surgical implants, though some bioceramics are flexible. It is also the class of ceramics that are being used for repair and replacement of diseased and damaged parts of the musculoskeletal system. 2.1 Types of bioceramics There are 3 classes of bioceramics  Nonabsorbable or relatively bioinert bioceramic.  Bioactive or surface-reactive ceramic.  Biodegradable or bioresorbable ceramic. Figure 2: Bioceramics used in biomedical application 4
  • 7. 2.1.1 Nonabsorbable or relatively bioinert bioceramic These ceramics maintain their physical and mechanical properties while in the host. They resist corrosion and wear even under high stress and extreme conditions. Relatively bioinert ceramics are typically used as structural–support implants, for example like bone plates, bone screws, and femoral heads. Example of bioinert bioceramic materials;  Alumina (Al2O3) It’s also known as Aluminium Oxides. Alumina has a rhombohedral structure. Alumina commonly been used in orthopaedics fields. It has high hardness at which is accompanied by low friction and inertness to the in-vivo environment. This property is one of the reasons why alumina can be used as an ideal material for the joint replacement.  Carbons (C) Carbon is one of the widely used components in biomaterial or medical fields. It can be made in many allotropic forms like graphite, crystalline diamond, monocrystalline glassy carbon and quasicrystalline pyrolitic carbon. The crystalline structure of carbon that being used in implant is similar to the graphite. Since, carbons exhibit good compatibility with body tissues, these materials have been used extensively for repairing diseased heart valves and blood vessels. 5 Figure 3: Femoral heads used in total hip replacements
  • 8. Figure 4: Application of Alumina as bone screws and bone plates 2.1.2 Biodegradable or bioresorbable ceramic Biodegradable or bioresorbable ceramic degrades upon implantation in the host. This will be done chemically by the body. The resorbed material will be replaced by endogenous tissues. The chemicals produced during the degradation must be able to be processed through the normal metabolic pathways of the body without evoking any deleterious effects. Calcium phosphates would be one of the most widely used biodegradable ceramics in medical fields especially in bone replacement. This is because due to its structures which resembles the bone minerals. There are 7 different forms of calcium phosphate that varies each other in terms of its Ca/P ratio, water content, pH, impurities and temperature. Calcium phosphates typically form a family compounds known as “apatites”. Below are some examples of apatites; a) Monocalcium phosphate monohydrate(MCPM) → Triclinic structure b) Dicalcium phophatre dehydrate(DCPC) → Monoclinic structure. 6 Bone PlateBone screw Figure 5: Scaffold and Dental implant screws
  • 9. Figure 6: Calcium phosphate being used in bone regeneration Figure 7: Application of Calcium Phosphates in Dental implants 7
  • 10. Figure 8: Injectable bone substitutes of hydroxyapatite used for orthopaedic trauma Figure 9: Calcium Phosphate as filler materials 8
  • 11. 2.1.3 Bioactive or surface-reactive ceramics These are ceramic or inorganic materials that upon implantation in the host form string bonds with the adjacent tissues. In simpler terms, bioactive ceramics are able to form chemical bonds directly to the host biological tissues. Sometime, the bioceramics like Hydroxyapatite (HA) also called as glass ceramics. This type of bioceramics is commonly used in replacement of damaged parts or tissue with synthetic or man-made parts or components. For example like being used in femoral knee or hip replacement. 2.2 The advantages and disadvantages of the bioceramic Pros Cons  Biological compatibility and activity  Brittle (low fracture resistance)  Less stress shielding  Low tensile strength  High corrosion or wear resistance  Poor fatigue resistance  High modulus (stiffness) and compressive strength  No disease transmission Table 1: Advantages and disadvantages of bioceramics 9 Figure 10: Hydroxyapatite (HA) used with metallic biomaterials in hip replacement
  • 12. 3.0 Tests on Biomaterials There are two types of tests for biomaterials, which are In Vitro testing and In Vivo testing. These tests are used to determine the biocompatibility and the longevity of the implants. These tests are also for the purpose of identifying the stability of an implant. Furthermore, these tests are mandatory in order to avoid any potential harmful effects to the host during or as it being used. As shown in figure 11, any newly designed biomaterial should undergo clinical trials. These biomaterials only can be used after it is screened through a series of in vitro biocompatibility testing. Once it is found to be non-toxic, it will be recommended for in vivo osseointegration tests. The in vivo tests essentially involve implanting the material in an animal model and the evaluation of its histocompatibility. This is followed by clinical trials in human patients. Both the animal and human trials mandatorily require approval from the institutional ethics committee. Figure 11: Steps involved in the translation of newly developed biomaterials from benchside to bedside. (Greeshma Thrivikramanab, Giridhar Madrasb and Bikramjit Basu) 10
  • 13. 3.1 In Vitro Test on Bioceramics Figure 12: Schematic illustration showing how nano/submicron particulates can be prepared, from starting bulk materials to study the toxicity of biomaterial eluates. 11
  • 14. The generation of wear debris and its accumulation in and around the implant are inevitable in the case of many prosthetic systems, due to mechanical stresses, as well as the continuous exposure to body fluids. Since the friction and wear of the implants strongly depend on the surrounding environment, the exposed surfaces will undergo chemical dissolution/degradation, either by the body fluids or by the foreign body reaction, elicited by invading immune cells. Hence to prevent this from happening and to measure the wear rates that affect the toxicity, in vitro testing will be carried out. As shown in figure 12, the first step towards the toxicity assessment of ultrafine particles is to synthesize finer particulates from bulk materials (biomaterials). Once such particles are prepared, one can prepare an eluate by dissolving such particles in phosphate buffered saline (PBS) or other medium. Furthermore, Fig. 12 shows the recommended sequence of various biochemical assays to evaluate the toxicity potential of biomaterial eluate. 12
  • 15. 3.2 In Vivo tests on Bioceramics Figure 13: Photomicrographs of host bone–implant interface after 14 weeks of implantation showing; (a) Bonding between bone and implant, without implant loosening/inflammation/implant gap, (b) Implant interface gap with less bone integration. Red arrow represents the blue stained region showing signs of inflammation and fibrosis, (c) The steps involved in the sample preparation for histopathological examination. 13
  • 16. In order to claim a newly developed material as an ideal implant, it must undergo extensive investigation (both in vitro and in vivo) to assess the biocompatibility, mechanical stability and safety. The results from short term in vitro studies can be difficult to extrapolate to the in vivo situation. Many biological reactions in vivo are rather complex. For this reason, the use of animal models is an essential step in the testing of orthopedic and dental implants, prior to clinical use in humans. In vivo tests allow the implanted material to come into contact with different cell types and also provide interactions with blood, proteins, enzymes and other hormones. Despite the availability of numerous animal models for testing the biological performance of implants, the choice of a suitable model is always crucial, based on the type of study. As the in vivo assessment of tissue compatibility of a biomaterial is focused on the end-use application, it must be noted that a biomaterial considered compatible for one application may not be compatible for another application. Fig. 13a shows an example of the histopathological structure and morphology of neobone formation at the interface between a natural bone and a synthetic polymer biocomposite. At the end of the implantation period of 4 weeks, a bone segment at the implant site was dissected and processed for histopathological observations (see Fig. 13c). The implant interface gap due to less bone integration is shown in Fig. 13b. The interfacial gap induces inflammation and fibrosis, that eventually hinders neo-osteogenesis (Fig. 13b). 14
  • 17. 4.0 Conclusion In summary, biomaterials are a growing field that focuses on the development of materials to replace or augment human tissues. Biomaterials play an essential role in medical field especially in tissue or parts replacement inside the living body. It is inert and famous for its biocompatibility against the host or the body immune system. Meanwhile, bioceramic are ceramics that have the properties of biomaterials and can be used medical applications that won’t cause any side or harmful effects to the host. Bioceramics are typically used as rigid materials in surgical implants, though some bioceramics are flexible. Nowadays, bioceramics are widely being used in bone transplants in the form of hydroxyapatite or calcium phosphate which might saves millions life. 15
  • 18. References [1] Biomaterials in orthopaedics (2016, Jan 2) Retrieved from https://www.slideshare.net/harivenkat1990/biomaterials-in-orthopaedics-ppt [2] Bioceramics (2017, August 24) Retrieved from https://en.wikipedia.org/wiki/Bioceramic [3] Biomaterials (2017, August 13) Retrieved from https://en.wikipedia.org/wiki/Biomaterial [4] Biomaterials – an overview (2014, June 26) Retrieved from https://www.slideshare.net/manishamanoharan/biomaterials-an-overview [5] In vitro/In vivo assessment and mechanisms of toxicity of bioceramic materials and its wear particulates (2014, March 5) Retrieved from http://pubs.rsc.org/en/content/articlehtml/2014/ra/c3ra44483j 16