BIOMEDICAL APPLICATIONS OF CERAMIC NANOMATERIALS: A REVIEW

Balasubramanian et al., IJPSR, 2017; Vol. 8(12): 4950-4959. E-ISSN: 0975-8232; P-ISSN: 2320-5148
International Journal of Pharmaceutical Sciences and Research 4950
IJPSR (2017), Volume 8, Issue 12 (Review Article)
Received on 22 March, 2017; received in revised form, 03 November, 2017; accepted, 12 November, 2017; published 01 December, 2017
BIOMEDICAL APPLICATIONS OF CERAMIC NANOMATERIALS: A REVIEW
Shivaramakrishnan Balasubramanian*1
, B. Gurumurthy 2
and A. Balasubramanian 3
Department of Pharmacology 1
, JSS College of Pharmacy, Udhagamandalam - 643001, Tamil Nadu, India.
Department of Radio Diagnosis 2
, JJM Medical College, Davanagere - 577004, Karnataka, India.
Department of Earth Sciences 3
, University of Mysore, Mysore - 570006, Karnataka, India.
ABSTRACT: A variety of Nano-biomaterials are synthesised,
characterised and tested to find out their potentialities by global scientific
communities, during the last three decades. Among those, nanostructured
ceramics, cements and coatings are being considered for major use in
orthopaedic, dental and other medical applications. The development of
novel biocompatible ceramic materials with improved biomedical
functions is at the forefront of health-related applications, all over the
world. Understanding of the potential biomedical applications of ceramic
nanomaterials will provide a major insight into the future developments.
This study reviews and enlists the prominent potential biomedical
applications of ceramic nanomaterials, like Calcium Phosphate (CaP),
Tri-Calcium Phosphate (TCP), Hydroxy-Apatite(HAP), TCP+HAP, Si
substituted HAP, Calcium Sulphate and Carbonate, Bioactive Glasses,
Bioactive Glass Ceramics, Titania-Based Ceramics, Zirconia Ceramics,
Alumina Ceramcis and Ceramic Polymer Composites.
INTRODUCTION: The field of nanotechnology
is playing a pivotal role in the fields of electronics,
biology and medicine. It also introduced several
new concepts into medicine and thus makes these
large cross disciplinary fields to join together.
Nanomedicine encompasses many common
technical issues like analytical tools, nanoimaging,
nanomaterials and nano-devices, novel therapeutics
and Drug Delivery Systems, clinical, regulatory
and toxicological issues. Among the varieties of
nanomaterials, nanostructured ceramics, cements
and coatings are being considered for major
applications in orthopaedic and dental treatments.
QUICK RESPONSE CODE
DOI:
10.13040/IJPSR.0975-8232.8(12).4950-59
Article can be accessed online on:
www.ijpsr.com
DOI link: http://dx.doi.org/10.13040/IJPSR.0975-8232.8 (12).4950-59
Biocompatible Ceramics, also known as
bioceramics, include of both macro and nano
materials mainly used for bone, teeth and other
medical applications. Understanding of the
potential biomedical applications of ceramic
nanomaterials will provide a major insight in to the
future developments. It is under this context, this
review has been made to enlist the potential
biomedical applications of ceramic nanomaterials 1
.
1.1 Nanomedicine: Applications of nano-
technology in several areas of biomedical fields
have provided a lot of opportunities and
possibilities for the growth of nanomedicine. The
major opportunities include superior diagnostic
tools and biosensors, improved imaging techniques,
innovative therapeutics and technologies to enable
tissue regeneration and repair. The long term
priorities are found to be in the design of synthetic,
bioresponsive systems for intracellular delivery of
macromolecular therapeutics (synthetic vectors for
Keywords:
Ceramic Nanomaterials,
Bioceramics, Biomedical
Applications, Nanomedicine,
Bioresponsive Systems
Correspondence to Author:
Mr. B. Shivaramakrishnan
Lecturer,
Department of Pharmacology,
JSS College of Pharmacy, „Rocklands‟,
PB no - 20, Udhagamandalam -
643001, Tamil Nadu, India.
E-mail: shivaram.krishna@jssuni.edu.in

gene therapy), and bioresponsive or self-regulated
delivery systems including smart nanostructures
such as biosensors that are coupled to the
therapeutic delivery systems 2
.
There is also an urgent need to more clearly
articulate and better communicate the potential
benefits of Nanomedicine to the budding
researchers as a whole. There are increasing
challenges within the pharmaceutical industry to
locate drugs more efficiently to their disease targets
and treat them effectively. The major techniques
and tools developed for analysis and diagnostics in
the medical field have the potential for wider
application 3, 4
.
1.2 Nanobiomaterials: Nanobiomaterials are
nanoscale materials utilized for various biological
and biomedical applications such as drug and gene
delivery, biosensors, bio-imaging, tissue
engineering, bio-electronics, and for antimicrobial
activities 5
. A variety of Nanobiomaterials are
synthesised, characterised and tested to find out
their potentialities by global scientific
communities, during the last four decades 6
. A
substantial amount of work has been carried out in
the field of nanobiomaterials 7, 8
.
The types of nanobiomaterials synthesized,
produced and used are very highly heterogeneous
with reference to their physical, chemical,
biological and engineering properties. They pose
not only many challenges in their design and
development, but also provide ample opportunities
to use them in several of the modern applications.
Huge repositories of literature collections are
available on the synthesis and characterisation
aspects 9 - 10
. Nanobiomaterials include a wide
range of nanoscale fine particles and devices that
are fabricated with a prime focus on biological and
biomedical applications 11
. The nanobiomaterials
are classified into the following subgroups 12
:
1) Metallic nanobiomaterials
2) Ceramic nanobiomaterials
3) Semiconductor based nanobiomaterials
4) Organic/carbon based nanobiomaterials
5) Organic inorganic hybrid nanobiomaterials
6) Silica based nanobiomaterials
7) Polymeric nanobiomaterials including nano
composites
8) Biological nanobiomaterials
9) Biologically directed / self-assembled nano-
biomaterials
10) Bionanomaterials such as nanodiamonds.
Among these, nanostructured ceramics, cements
and coatings are being considered for major
orthopaedic, dental and other medical applications.
The development of novel biocompatible ceramic
materials with improved biomedical functions is at
the forefront of health-related applications all over
the world. Ceramics are also unique biomaterials
used for repairing and regenerating several parts of
the human body 13
. Modern ceramic substrates and
packages are sophisticated combinations of glasses,
ceramics, and metals that can form compact cost-
effective solutions for a variety of applications 14
.
In this work, the prominent applications of only the
ceramic nanomaterials are discussed.
1.3 Properties of Ceramic Nanobiomaterials:
Ceramics are compounds between metallic and
non-metallic elements; they are most frequently
oxides, phosphates, nitrides, and carbides. There
are wide range of ceramic materials like clay
minerals, cement, and glass used for various
applications 15
. These materials are typically
insulative to electricity and heat, and are highly
resistant to harsh chemical environments than
metals and polymers. With regard to their
mechanical behaviour, ceramics are very hard and
brittle. At nanoscale also, ceramic materials exhibit
higher hardness, excellent heat and corrosion
resistance, and electrical insulation properties 16
.
Typical examples include china clay, firebricks,
cements and glass. In addition to these properties,
Fine Ceramics (also known as “advanced
ceramics”) have many advanced mechanical,
electrical, electronic, magnetic, optical, chemical
and biochemical characteristics. One of the major
field of application of bioceramics is tissue
generation. The major parameters considered to
optimize the biomaterials for tissue generation
include 17
, a) Structural Components (physical,
mechanical and chemical properties) and b)
Biochemical Components (immobilized signals,
diffusable signals, and living components).
The bioceramics have good biocompatibility, osteo
conductivity, osteoinductivity, biodegradability,

resorbability, and hydrophilicity. Yet another major
field of application of bioceramic is clinical
dentistry.
2.0 Types of Ceramic Nanobiomaterials: The
widely used ceramic nanobiomaterials include Fig.
1, Calcium Phosphate (CaP), Tri-Calcium
Phosphate (TCP), Hydroxy-Apatite(HAP),
TCP+HAP, Si substituted HA, Calcium Sulphate
and Carbonate, Bioactive Glasses, Bioactive Glass
Ceramics, Titania-Based Ceramics, Zirconia
Ceramics, Alumina Ceramcis and Ceramic Polymer
Composites.
FIG. 1: WIDELY USED CERAMIC NANOBIOMATERIALS
Biomaterials are mainly used for orthopaedic
applications 18
. Bioceramics are materials used to
repair and replacement of diseased and damaged
parts of musculoskeletal systems. Based on their
inherent properties, they are classified into three
major categories as 19
:
a) Bioactive ceramics (CaP, HAP, Bioactive Glass
(BAG), and Glass Ceramics (GC) which form
direct chemical bonds with bone or even soft
tissues of living systems, b) Bioresorbable ceramics
(TCP) that actively participate in the metabolic
process of an organism andc) Bioinert high strength
ceramics (alumina and zirconia)
Based on their applications, ceramic biomaterials
are further classified into:
a) Cardiovascular biomaterials
b) Dental Biomaterials
c) Orthopedic bomaterials
d) Biomaterials to promote tissue generation.
Nanomaterials of CaP, HAP, TCP, BAG, GC and
Calcium sulphate form good ceramic-based bone
graft substitutes.
2.2 Applications of Ceramic Nanobiomaterials:
2.2.1 Calcium Phosphate (CaP): Calcium plays a
very important role in the body. It is necessary for
normal functioning of nerves, cells, muscles, and
bones. If there is not enough calcium in the blood,
then the body will take calcium from bones,
thereby weakening bones. Tooth enamel is
composed of almost ninety percent hydroxyapatite.
Its solubility in cold water is 2 mg / 100 cc.
The Calcium phosphates occur abundantly in
nature in several forms as:
a) Monocalcium phosphate - Ca(H2PO4)2 occurring
as monohydrate
b) Dicalcium phosphate (dibasic calcium
phosphate), CaHPO4 named as Dihydrate
c) Tricalcium phosphate (tribasic calcium
phosphate or tricalcic phosphate), Ca3(PO4)2,
also named as calcium orthophosphate
d) Hydroxyapatite Ca5(PO4)3(OH)
e) Apatite Ca10(PO4)6(OH, F, Cl, Br)2
f) Octacalcium phosphate Ca8H2 (PO4)6. 5H2O
g) Tetracalcium phosphate, Ca4 (PO4)2O.

Calcium Orthophosphates have very useful
properties and show several major biomedical
applications. Regardless of the composition, all
calcium phosphates are osteoconductive. Bone,
which is similar to other calcified tissues, is an
intimate composite of the organic (collagen and
noncollagenous proteins) and inorganic or mineral
phases 20
.
The bioactivity and degradation behavior generally
depend on the Ca/P ratio, crystallinity and phase
purity. The biological calcium phosphates are
mainly observed as components of natural hard
tissues, that is, bone and teeth 21
. Ceramic
nanobiomaterials, especially, calcium phosphate
are used mainly as bone substitutes or scaffolds due
to their good biocompatibility and also due to their
compositional similarity with the inorganic
components of human bone 22
. The major limitation
of calcium phosphate- based ceramics lies in its
load-bearing capability and their mechanical
properties like brittleness, and poor fatigue
resistance. Such factors are generally inadequate
for many load-carrying applications 23
.
Calcium Phosphate (CaP) biomaterials are used in
the form of nanoparticles, coatings, cements, and
scaffolds mainly in orthopedic and dental
applications 24
. They are able to bind and
concentrate bone morphogenetic proteins that are in
circulation and may become osteoinductive
(capable of osteogenesis) and can be effective
carriers of bioactive peptide or bone cell seeds 25
.
CaP biomaterials have outstanding properties based
on which they are used for several kinds of
biomedical applications 26, 27
.
The current applications also include replacements
for hips, knees, teeth, tendons and ligaments, as
well as repair for periodontal disease, maxillofacial
reconstruction, augmentation and stabilization of
the jawbone, spinal fusion and bone fillers after
tumor surgery 28
.
The biphasic, triphasic and multiphasic
(polyphasic) calcium orthophosphates are good
biomaterials for reconstruction of bone defects in
maxillofacial, dental and orthopedic applications 29
.
The major applications of calcium phosphates are
found to be:
a) Bone Grafts, Bone Reconstruction and Repair:
Bone-grafting is usually required to stimulate bone-
healing. In addition, spinal fusions, filling defects
following removal of bone tumors and several
congenital diseases may require bone grafting 30 -
32
.
b) Bioactive Coatings for Orthopaedic Implants 33, 34
.
c) Controlled Drug Release: Ceramics can be
effective carriers of bioactive peptide or bone cell
seeds and are therefore potentially useful in tissue
engineering and drug delivery.
The calcium phosphate cements are used as carriers
of different types of drugs, such as antibiotics,
analgesics, anticancer and anti-inflammatory drugs
35 - 37
. The bioactive bone scaffolds are used as
therapeutic drug carriers 42, 43
,
d) Gene delivery and gene therapy 44, 45
e) Dentistry
f) Bone tissue regeneration.
2.2.2 Tri-Calcium Phosphate: Tricalcium
phosphate (TCP) is one of the most common and
important members of the calcium phosphate
family of minerals, which are made of calcium
cations with different phosphate anions such as
orthophosphates, metaphosphates or pyrophosphates.
TCP is practically insoluble in water; insoluble in
ethanol, soluble in dilute hydrochloric and nitric
acid. It has three crystalline polymorphs α, α' and β.
The α and α' states are formed at high temperatures.
The α-tricalcium phosphate (α-TCP, α-Ca3(PO4)2)
is receiving growing attention as a raw material for
several injectable hydraulic bone cements,
biodegradable bioceramics and composites for
bone repair 46
. Tricalcium phosphate materials
mostly behave like osteoconductive materials,
which permits bone growth on their surface or into
pores, channels, or pipes. It is a resorbable phase.
Calcium phosphate exhibits some good properties
to support bone growth 47
. The major field of
applications are a) bone implant and replacement
applications 48
and b) tissue engineering 49
.
2.2.3 Hydroxy-Apatite (HAP): Hydroxyapatite
(HAP) has been widely used as a biocompatible
ceramic in many areas of medicine, but mainly for
contact with bone tissue, due to its resemblance to

mineral bone. HAP has exceptional
biocompatibility and bioactivity properties with
respect to bone cells and tissues. As a result of
excellent favorable osteoconductive and bioactive
properties, it is widely preferred as the biomaterial
of choice in both dentistry and orthopaedics 50, 51
.
The hydroxyapatite has a few favorable bioactive
and osteoconductive properties which help in rapid
bone formation, with a strong biological fixation to
bony tissues. It also has very low mechanical
strength and fracture toughness, which is an
obstacle to its applications in load-bearing areas 52
.
Due to its outstanding properties, the HAPs are
employed in a variety of applications. They are 53
:
1. Bone tissue engineering, bone void fillers for
orthopaedic, traumatology, spine, maxillofacial
and dental surgery, orthopedic and dental
implant coating,
2. Repair of mechanical furcation perforations and
apical barrier formation,
3. Desensitizing agent in post teeth bleaching,
4. Early carious lesions treatment, and drug and
gene delivery.
Biomedical Applications of Hydroxyapatite
Nanoparticles 54
include
a. Bone regeneration and bone tissue engineering
applications 55, 56
b. Osteoblast and dental adhesion 57, 58
c. Repair of dental enamel 59
d. Controlled - release carrier of bone
morphogenetic protein 60
e. Intracellular Bio-imaging 61
f. Photocatalytic applications 62
g. Antibacterial applications 63
h. Drug Delivery Systems.
HAP can incorporate the drug molecules either
physically or chemically so that the drug retains
intact until it reaches to the target site. It could also
gradually degrade and then deliver the drug in a
controlled manner over time 64, 65
.
2.2.4 TCP+HAP: TCP and HA are used together
since they both have bioactiveness and
resorbability. Pure HA or TCP are not
osteoinductive. Sintered hydroxyapatite-tricalcium
phosphate (HA-TCP) ceramic material has more
biomedical applications 66
.
2.2.5 Si Substituted HAP: Silicon (Si) substitution
in the crystal structures of calcium phosphate (CaP)
ceramics such as hydroxyapatite (HAP) and
tricalcium phosphate (TCP) generates materials
with superior biological performance. Silica is an
essential trace element required for healthy bone
and connective tissues. It influences the biological
activity of CaP materials by modifying material
properties. Silica has direct effects on the
physiological processes in the skeletal tissue 67 - 69
.
The two main applications of silica-based materials
in medicine and biotechnology are seen in bone-
repairing devices and for drug delivery systems 70 -72
.
2.2.6 Calcium Sulphate and Carbonate: Calcium
sulfate (CS) is well-tolerated when used to fill bone
defects and undergoes rapid and complete
resorption without eliciting any significant
inflammatory response. It is also used as a vehicle
to deliver antibiotics. It is a good pharmacologic
agents 73
. It has found wide use in orthopedics and
dentistry, and has been used in a variety of clinical
applications, including the periodontal defect
repair, the treatment of osteomyelitis, sinus
augmentation, and as an adjunct to dental implant
placement 74, 75
. It has been found widely used in
orthopedics and dentistry 76
. Calcium Sulphate
Ceramics is a promising material for spinal cord
scaffold fabrication. Since it is biodegradable, it
has sufficient strength, and allows loading 77 - 80
.
2.2.7 Bioactive Glasses (BG): Bioactive glasses
are considered as attractive materials for
biomedical applications. Materials consisting of
calcium, phosphorous and silicate are classified as
Bioactive Glasses (BG). These BGs are dense and
hard. Most of the bioactive glasses have the
characteristics of osteointegration and osteo-
conduction. Bioactive glasses (BG) show great
promise for bone tissue engineering based on their
key properties, e.g. biocompatibility, bio-
degradability, osteo-conductivity as well as
osteogenic and angiogenic potential, which make
them excellent candidates for bone tissue scaffolds
and bone substitute materials. One of the most
interesting features of BG is their ability to bond
both to soft and hard tissues, depending on their
composition 81
.
Bioactive glass coatings are used for orthopaedic
metallic implants 82
. A new class of bioactive glass,

referred to as mesoporous bioglass (MBG), was
developed 7 years ago, which possess a highly
ordered mesoporous channel structure and a highly
specific surface area 83
. Tissue engineering and
Coatings for orthopaedic application are very
promising fields in nanomedicine.
2.2.8 Bioactive Glass Ceramics: The recent
studies include the development of bioactive
biomaterials for bone regeneration. Development of
sintered Na-containing bioactive glasses, borate -
based bioactive glasses, and those doped with trace
elements like Cu, Zn and Sr have been employed
for bone tissue engineering 84
.
2.2.9 Titania-Based Ceramics: Titanium comes
under the category of Technical ceramics. The
technical ceramics are divided into oxides and non-
oxides like Aluminium Oxide, Ceramics, Carbide
Ceramics, Nitride Ceramics, Oxide Ceramics,
Silicon Carbide Ceramics, Silicon Nitride
Ceramics, and Zirconium Ceramics Dioxide. The
fact that titanium is strong, light, non-toxic and
does not react without bodies makes it a valuable
medical resource and used to make surgical
implements and implants, such as hip joint
replacements that can stay in place for up to 20
years. Although other photocatalytic materials are
available, researchers have found that titanium
dioxide provides the best performance in sunlight.
Titanium nanomaterials has been clinically
successful as an orthopedic or dental implant
material.
2.2.10 Zirconia Ceramics: Zirconia Ceramics
include Zirconium Dioxide Ceramics / Zirconia
Ceramics / ZrO2. Zirconium dioxide nanoparticles
appear in the form of a white powder. It is non-
magnetic and highly resistant against acids. It has a
high thermal stability and has been proven to have
excellent compatibility with bones and the
surrounding connective tissue. The zirconium
dioxide nanoparticles are non-toxic to the
environmental organisms. The field of dentistry
makes use of its special properties for
manufacturing corona frames and bridge frames,
tooth root studs, and metal-free dental implants.
The major applications include
a) Coatings for metallic orthopaedic implants 85
b) Stabilize Hydroxyapatite 86
c) Dentistry 87
.
2.2.11 Alumina Ceramics: Technical Ceramics
includes mainly includes Aluminium oxides. It has
very outstanding physical stability due to its high
melting point (2050 °C), the highest hardness
among oxides. It is strong and heat-resistant. It is
the most widely used as the best-known fine
ceramic material. The major applications of
aluminium oxide ceramics include,
a) Dentistry
b) Anthroplasty
c) Treatment of hand and elbow fractures and
d) Antimicrobial activities 88
2.2.12 Ceramic Polymer Composites: Ceramics
have been successfully used for several decades for
orthopædic prostheses. Ceramic composites are
materials made from two or more constituent
materials with significantly different physical or
chemical properties. Currently, composites of
polymers and ceramics are being developed with
the aim to increase the mechanical scaffold stability
and to improve tissue interaction. Limitations also
exist with the difficulties of commercialisation, due
to the scalability and the cost/benefits ratio 89
. A
variety of bioactive composites have been
investigated over the last two decades as substitute
materials for diseased or damaged tissues in the
human body. These ceramic nanobiomaterials are
mainly used in, bone tissue engineering 91, 92
,
dentistry 93 - 98
and hip joint replacements 99
.
2.2.13 Other Ceramic Nanobiomaterials:
Magnetic oxides are also used in association with
ceramic nanomaterials for therapeutic drug, gene
and radionuclide delivery, cancer therapy and as
contrast enhancing agents 100
.
CONCLUSION: Applications of nanotechnology
in several areas of biomedical fields have provided
a lot of opportunities and possibilities for the future
of nanomedicine. There are wide range of ceramic
materials like clay minerals, cement, and glass used
for various applications. Biocompatible Ceramics,
also known as bioceramics, are mainly used for
bone, teeth and other medical applications. The
bioceramics have good biocompatibility, osteo-
conductivity, osteoinductivity, biodegradability,
resorbability, and hydrophilicity. the widely used
ceramic nanobiomaterials are Calcium Phosphate
(CaP), Tri-Calcium Phosphate (TCP), Hydroxy-

Apatite (HAP), TCP+HAP, Si substituted HAP,
Calcium Sulphate and Carbonate, Bioactive
Glasses, Bioactive Glass Ceramics, Titania-Based
Ceramics, Zirconia Ceramics, Alumina Ceramcis
and Ceramic Polymer Composites.
It is found that all these have shown a lot of
applications in nanomedicine, orthopedics,
dentistry, bone regeneration, tissue development
and other biomedical activities in human body.
Ceramic nanobiomaterials have excellent
applications in several areas of health and
medicine, and have a promising future in all
commercial applications of nanotechnology.
ACKNOWLEDGEMENT: The first author
thanks Dr. B. Suresh, the Vice Chancellor, JSS
University, Mysuru, and Dr. S. P. Dhanapal, the
Principal, Dr. K. Elango and his colleagues at the
J.S.S. College of Pharmacy, Udhagamandalam, for
providing all the support and encouragements to do
this work. The second author thanks the Principal /
Director of J.J.M. Medical College, Davanagere,
and the Head and other senior faculty members,
batchmates of the Department of Radiology for
their encouragement during this work. Professor A.
Balasubramanian, former Dean, Faculty of Science
and Technology, University of Mysore, thanks all
his colleagues for their encouragement during this
work.
CONFLICT OF INTEREST: Nil.
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Balasubramanian S, Gurumurthy B and Balasubramanian A: Biomedical applications of ceramic nanomaterials: A review. Int J Pharm Sci
Res 2017; 8(12): 4950-59.doi: 10.13040/IJPSR.0975-8232.8(12).4950-59.

BIOMEDICAL APPLICATIONS OF CERAMIC NANOMATERIALS: A REVIEW

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