Chapter 2

Implantable Medical Devices

Wahid Khan, Eameema Muntimadugu, Michael Jaffe,
and Abraham J. Domb

Abbreviations
MEMS
NEMS
PCL
PET
PGA
PLA
PU
PTFE
PMMA
UHMWPE

Microelectromechanical systems
Nano-electromechanical systems
Polycaprolactone
Polyethylene terephthalate
Polyglycolic acid
Polylactic acid
Polyurethane
Poly(tetrafluoroethylene)
Polymethylmethacrylate
Ultrahigh molecular weight polyethylene

W. Khan E. Muntimadugu
Department of Pharmaceutics, National Institute of Pharmaceutical Education
and Research (NIPER), Hyderabad 500037, India
M. Jaffe
Medical Device Concept Laboratory, New Jersey Institute of Technology, Newark, NJ, USA
A.J. Domb (*)
Faculty of Medicine, Institute of Drug Research, School of Pharmacy,
The Hebrew University of Jerusalem, Jerusalem 91120, Israel
e-mail: avid@ekmd.huji.ac.il
A.J. Domb and W. Khan (eds.), Focal Controlled Drug Delivery, Advances
in Delivery Science and Technology, DOI 10.1007/978-1-4614-9434-8_2,
Controlled Release Society 2014

33

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2.1

W. Khan et al.

Introduction

Each year millions of patients improve their quality of life through surgical
procedures that involve implanted medical devices. The term implant is used for
devices that replace or act as a fraction of or the whole biological structure. Currently,
implants are being used in many different parts of the body for various applications
such as orthopaedics, pacemakers, cardiovascular stents, defibrillators, neural prosthetics or drug delivery system [1]. Concurrent with the increased life span in
todays world, the number of age-related diseases has also increased. Hence, the
need for new treatments, implants, prostheses and long-term pharmaceutical usage
as well as the need for prolonging the life span of the current techniques has
increased [2]. Joint diseases represent one of the examples of changing needs in the
medical treatment: Todays estimates show that 90 % of the population over the age
of 40 suffers from a degenerative joint disease [3]. In 2000, the number of total hip
replacements operation was about 152,000 which represents a 33 % increase from
the number of operations in 1990 and also represents about half of the estimated
number of operations by 2030 [4]. Cardiovascular diseases are another example.
Over the last two decades, coronary stents have become a new standard in angioplasty procedure. In 2004, the number of implanted drug-eluting stents alone
exceeded two million [5]. In-stent restenosis is a consequence almost entirely of
tissue hyperplasia, occurring principally around the points where the stent struts
impinge upon the artery wall. Less common, but troublesome when it occurs, is
subacute thrombosis, a complication not quite eliminated by modern stent deployment techniques and antiplatelet agents. By carrying a coating or drug targeted at
the thrombotic or hyperplastic responses occurring locally, drug-eluting stents present a solution to the above problems [6].

2.2

Classes of Implantable Medical Devices

The regulatory authorities recognise different classes of medical devices, based on

their design complexity, their use characteristics and their potential for harm if misused. Each country or region defines these categories in different ways. The authorities also recognise that some devices are provided in combination with drugs, and
regulation of these combination products takes this factor into consideration. The
FDA classification of medical devices is based upon the level of control required to
assure safety and effectiveness of the device [7]. The classification procedures are
described in the Code of Federal Regulations, Title 21, part 860 (usually known as
21 CFR 860).
Class I devices are subject to the least regulatory control general controls. Class
I devices are not intended for use in supporting or sustaining life or to be of substantial importance in preventing impairment to human health, and they may not present
a potential unreasonable risk of illness or injury. Examples of class I devices include

2 Implantable Medical Devices

35

elastic bandages, examination gloves and hand-held surgical instruments. Class II

devices are those for which general controls alone are insufficient to assure safety
and effectiveness, and existing methods are available to provide such assurances. In
addition to complying with general controls, class II devices are also subject to special controls. A few class II devices are exempt from the premarket notification.
Special controls may include special labelling requirements, mandatory performance
standards and postmarket surveillance. Examples of class II devices include powered
wheelchairs, infusion pumps and surgical drapes. Class III device is one for which
insufficient information exists to assure safety and effectiveness solely through the
general or special controls sufficient for class I or class II devices. Such a device
needs premarket approval, a scientific review to ensure the devices safety and effectiveness, in addition to the general controls of class I. Class III devices are usually
those that support or sustain human life and are of substantial importance in preventing impairment of human health or those which present a potential, unreasonable
risk of illness or injury. Examples of class III devices include implantable pacemaker, pulse generators, HIV diagnostic tests, automated external defibrillators and
endosseous implants. Most of the devices discussed in this chapter will belong to
class III. These are mostly implants in the orthopaedic, dental, ophthalmic and cardiovascular fields as well as soft tissue implants such as implants used in plastic
surgery. Implants without bioactive coatings intended to secure teeth or prostheses to
the maxillary or mandibular bones, and implants intended to be placed in teeth such
as bridges, crowns, dental filling materials and dental alloys belong to class II [8].
Based on the purpose for which they are using, these implantable devices are
broadly divided into three classes: cardiovascular implants, orthopaedic implants
and implants for other use. Various subcategories under these classes are given in
Table 2.1.

2.2.1

Cardiovascular Implants

Cardiovascular implants have strong potential to reduce the overall treatment cost
for heart disease and at the same time contribute significantly to improved quality of
life. Pacing devices will realise the greatest sales gains, largely due to growth in
cardiac resynchronisation therapy. A focus on developing new generations of pacing devices that reduce mortality and improve patient outcomes has resulted in
greater pricing flexibility in an increasingly cost-conscious health-care environment. Demand for cardiovascular stents and related devices will be similar to that of
demand for pacing devices. The fastest growth will be in structural implants, as
technological advances in heart valves, ventricular assist devices and implantable
monitors will encourage greater use.
Cardiovascular disease broadly covers a range of conditions affecting both the
heart and the blood vessels. Polymer-coated and polymer-based cardiovascular
implants are essential constituents of modern medicine and will proceed to gain
importance with the demographic changes toward a society of increasing

W. Khan et al.

36
Table 2.1 Classification of implantable medical devices
Orthopaedic implants
Reconstructive joint
replacementsa
Knee replacements
Hip replacement implants
Other reconstructive joint
replacements
Shoulder implants
Elbow implants
Ankle implants
Joint replacements
Spinal implantsa
Thoracolumbar implants
Intervertebral spacers
Motion preservation
devices
Cervical implants
Implantable spinal
stimulators

Cardiovascular implants
Pacing devicesb
Cardiac resynchronisation
therapy devices
Implantable
cardioverter-defibrillators
Implantable cardiac
pacemakers
Pacing accessoriespacing
leads, pacing batteries
Cardiac stents and related
implantsb,c
Coronary stents
drug-eluting stents,
bare-metal coronary stents
Stent-related implants
Synthetic graftsvascular
grafts, peripheral grafts
Vena cava filters
Structural cardiac implantsa
Heart valves and accessories
Tissue heart valves
Ventricular assist devices
Implantable heart monitors
Insertable loop recorders
Implantable hemodynamic
monitors

Orthobiologicsb
Hyaluronic acid
Bone substitutes
Bone growth factors
Bone cement
Trauma implantsb
Internal fixation devices
Craniomaxillofacial
implants
Implantable trauma
stimulators
a
Structural and mechanical support
b
Functional support
c
Localised drug delivery

Other medical implants

Otolaryngeal implantsb,c
Cochlear implants
Airway and oesophageal
stents
Cosmetic implantsbreast
implants
Ophthalmic implantsb
Intraocular lenses
Glaucoma and other lenses
Neurostimulatorsb
Gastroenterological implantsb
Gastric bands
Biliary stents
Urological implants

Gynaecological devicesb
Soft tissue repair
Intrauterine devices

Drug implantsc
Hormonal implants
Brachytherapy products
Implantable drug pumps

age-related morbidity. Based on the experiences with implants such as coronary or

peripheral stents, which are presently widely used in clinical medicine, several
properties of the next generation of cardiovascular implants have been envisioned
that could be fulfilled by multifunctional polymers. The challenge is to combine
tailored mechanical properties and rapid endothelialisation with controlled drug
release in order to modulate environmental cells and tissue. Additionally, degradability and sensitivity to external stimuli are useful in several applications. A critical
function in terms of clinical complications is the haemocompatibility. The design of
devices with improved haemocompatibility requires advanced in vitro test setups as
discussed in depth in this article. Finally, degradable, multifunctional shape-memory
polymers are introduced as a promising family of functional polymers that fulfil
several requirements of modern implants and are of high relevance for

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37

cardiovascular application (e.g. stent technology). Such multifunctional polymers

are a technology platform for future cardiovascular implants enabling induced
auto-regeneration in regenerative therapies [9]. Shape-memory materials have been
proposed for cardiovascular stents due to their self-expansion ability. The most ideal
way to anchor a stent is using self-expansion in the range of body temperature. Ajili
et al., for the first time, report the use of polyurethane/polycaprolactone (PU/PCL)
blend as a proposed material for shape-memory stents. The results showed that the
blend supported cell adhesion and proliferation, which indicated good biocompatibility, and the results suggested that this blend might be a potential material as a
stent implant [10]. Multifunctional shape-memory polymers are highlighted as a
class of materials that combine biocompatibility and the capability for stimuliinduced active movements for anchoring of implants with a controlled degradation
and drug release profile to enable a functional regeneration of the tissue at the application site. The challenge is to combine tailored mechanical properties and rapid
endothelialisation with controlled drug release in order to modulate environmental
cells and tissue. Additionally, degradability and sensitivity to external stimuli are
useful in several applications [11]. Current cardiovascular therapies are limited by
the loss of endothelium, restenosis and thrombosis. Andukuri et al. reported biomimetic hybrid nanomatrix that combined the unique properties of electrospun PCL
nanofibres with self-assembled peptide amphiphiles. Results indicate that this
hybrid nanomatrix has great potential application in cardiovascular implants [12].

2.2.2

Orthopaedic Implants

Orthopaedic implants will remain the largest implantable device segment in market
value. Gains will also reflect the growing prevalence of degenerative musculoskeletal disorders and lifestyle changes that place people at risk for sports and exercise
injuries. At the same time, as products become more durable and long-lived, demand
will increasingly come from an enlarged patient base for new surgeries rather than
for replacements. Also challenging this segment over the long term will be advances
in pharmaceutical alternatives to treat arthritic conditions. However, the segment
will benefit from a strong base of insurance approvals for orthopaedic implants, as
well as a stable and well-funded medical delivery system and product designs that
allow for less invasive surgeries.
One of the most prominent application areas for biomaterials is for orthopaedic
implant devices. Both osteoarthritis and rheumatoid arthritis affect the structure of
freely movable (synovial) joints, such as the hip, knee, shoulder, ankle and elbow.
The pain in such joints, particularly weight-bearing joints such as the hip and knee,
can be considerable, and the effects on ambulatory function quite devastating. It has
been possible to replace these joints with prostheses since the advent of anaesthesia,
antisepsis and antibiotics and the relief of pain and restoration of mobility is well
known to hundreds of thousands of patients [13].

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W. Khan et al.

Total joint replacement is widely regarded as the major achievement in orthopaedic

surgery in the twentieth century. Arthroplasty, or the creation of a new joint, is the
name given to the surgical treatment of degenerate joints aimed at the relief of pain
and the restoration of movement. This has been achieved by excision, interposition
and replacement arthroplasty and by techniques that have been developed over
approximately 180 years. In a total knee arthroplasty, the diseased cartilage surfaces
of the lower femur (thighbone), the tibia (shinbone) and the patella (kneecap) are
replaced by a prosthesis made of metal alloys and polymeric materials. Most of the
other structures of the knee, such as the connecting ligaments, remain intact [3].

2.2.3

Other Implants

Evolution of cochlear implant technology resulted in enhanced hearing, speech and

cost-effectiveness for children. Binaural cochlear implantation has been used in
children. Development of perimodiolar electrodes, implantable microphones and
rechargeable batteries promise fully implanted devices in future [14].
Intraocular sustained drug release using implantable devices has been investigated to treat vitreoretinal diseases. Possible targeted diseases include those in
which repeated intraocular injections are effective (cytomegalovirus retinitis, uveitis), diseases requiring surgery (proliferative vitreoretinopathy) and chronic diseases (macular oedema, retinitis pigmentosa). Hydrophobic or hydrophilic polymers
shaped into a sheet, disc, rod, plug or a larger device can be implanted into the
subretinal space, intrascleral space, vitreous space or peribulbar space or at the pars
plana [15].
Solid biocompatible implantable devices for sustained or controlled intravitreal
drug delivery to the posterior segment of the eye have been developed employing
diverse approaches and include osmotic mini-pumps, nonbioerodible and bioerodible drug-loaded pellets, configured capillary fibres, biodegradable scleral plugs,
scleral discs, polymeric matrices and scaffolds of various geometries providing
unique mechanisms of drug release for the delivery of drugs to the posterior segment
of the eye [16].

2.3

Materials Used for Medical Devices

In general, most of the materials used for implants or devices can be divided into the
following categories: metals, polymers and ceramics. Metals are based on the metallic bond, ceramics are based on ionic bonds, and polymers are based on covalent
bonds; and each of these categories contains many subdivisions. The metallic materials include pure metals and alloys; ceramics include glasses, glassceramics and
carbons; and the polymers include thermosets, thermoplastics, elastomers and textiles. As biomaterials science emerged, the conventional view of materials, as being

2 Implantable Medical Devices

39

tangible pieces of substances from which useful objects were made, prevailed [17].
The best performance of the vast majority of implantable devices is achieved when
the biomaterials used in their construction are chemically and biologically inert; no
biological, let alone pharmacological, activity should be sought in these devices.
However, at least in theory, there are some exceptions, with the intention of either
promoting some biological activity such as bone regeneration or minimising undesirable activity such as infection or blood clotting. Some materials are used with the
express intention of delivering some biologically or pharmacologically active agent
to the patient; the concept of drug delivery devices is of course well known [18].

2.3.1

Metals

As a class of materials, metals are the most widely used for load-bearing implants.
These range from simple wires and screws to fracture fixation plates and total joint
prostheses (artificial joints) for the hips, knees, shoulders, ankles and so on. In addition to orthopaedics, metallic implants are used in maxillofacial surgery and cardiovascular surgery and as dental materials. Although many metals and alloys are used
for medical device applications, the most commonly employed are stainless steels
[19, 20], cobalt-base alloys, commercially pure titanium and titanium alloys and
some other metals [21]. Various properties of these metallic implant materials are
listed in Table 2.2.
Stainless steels are iron-base alloys, and stainless characteristics are achieved
through the formation of an invisible and adherent chromium-rich oxide surface
film. This passive film serves as a barrier to corrosion processes in alloy systems that
would otherwise experience very high corrosion rates and has the ability of selfhealing, when damaged, as chromium in the steel reacts with oxygen and moisture
in the environment to reform the protective oxide layer. Based on the characteristic
crystallographic structure/microstructures of the alloys, stainless steels are classified
into four classes: martensitic, ferritic, austenitic and duplex (austenitic plus ferritic).
Stainless steels are used extensively for fracture fixation devices. Compared to the
other metals used in orthopaedics, stainless steels exhibit a moderate to high elastic
modulus and tensile strength. Additionally, these steels possess good ductility, which
allows them to be cold worked. Stainless steels are fairly biocompatible although
they never appear to fully integrate with bone or soft tissue. For instance, if stainless
steel is placed in close proximity of bone in the body, a thin layer of fibrous tissue
will intervene between the bone and metal at the microscopic level. This phenomenon is not conducive to the use of stainless steels in applications where the success
of the implant is dependent on its close integration with tissue [22].
Cobaltchromium alloys are highly corrosion resistant. Compared to stainless
steel, they exhibit higher elastic modulus, strength and hardness, but they have relatively low ductility and are difficult to machine. Commonly used cobalt alloys are
Co-28Cr-6Mo casting alloy, Co-20Cr-15W-10Ni wrought alloy, Co-28Cr-6Mo
thermomechanically processed alloy and Co-35Ni-20Cr-10Mo wrought alloy.

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W. Khan et al.

Table 2.2 Comparison of some of the characteristics and mechanical properties of metallic
implant materials [22]
Grade
Composition

Youngs modulus
(GPa)
Tensile strength
(MPa)
Advantages

Disadvantages

Uses

Stainless steels
Austenitic stainless
steel
Fe
Cr (1720)
Ni (1214)
Mo (24)
200

Cobalt-base alloys
Cobaltchromium
alloy
Co
Cr (1930)
Mo (010)
Ni (037)
230

Ti and Ti-base alloys

alloy

5401,000

9001,540

900

Cost, availability,
processing

Wear resistance,
corrosion resistance,
fatigue strength

Long-term
behaviour,
high modulus
Temporary devices
(fracture plates,
screws, hip nails);
used for total hip
replacement

High modulus,
biocompatibility

Biocompatibility,
corrosion, minimum
modulus, fatigue
strength
Lower wear resistance,
low shear strength

Dentistry castings,
prostheses stems,
load-bearing components in total joint
replacement

Used in THRs with

modular femoral
heads; long-term
permanent devices
(nails, pacemakers)

Ti
Al (6)
V (4)
Nb (7)
106

They possess adequate fatigue properties to serve as artificial joints or total joint
prostheses and are used extensively for this purpose.
Commercially pure titanium is well known for its excellent corrosion resistance.
Various grades of unalloyed titanium are available with oxygen and iron as primary
variants. Biomedical applications for commercially pure titanium grades include
pacemaker cases, housings for ventricular assist devices, implantable infusion drug
pumps, dental implants, maxillofacial and craniofacial implants and screws and
staples for spinal surgery. Superior biocompatibility, enhanced corrosion resistance
and lower modulus are some of the attractive properties of titanium-base alloys as
biomaterials. Based upon their microstructure after processing, titanium-base alloys
are divided into four classes: , near , and . Femoral hip stems, fracture fixation plates, spinal components, fasteners, intramedullary nails and screws are some
of the biomedical applications of these alloys [23].
Among the various refractory metals, niobium, molybdenum and tungsten are
used as alloying elements in stainless steels, cobalt-base alloys and titanium-base
alloys [24]. Tantalum has excellent resistance to corrosion and also offers intrinsic
fabrication advantages. Apart from the alloying additive, commercially pure tantalum is fabricated into various medical devices such as foils and sheets for nerve
anastomoses, clips for ligation of vessels and staples for abdominal surgery and as
pliable sheets and plates for cranioplasty and reconstructive surgery [25].

2 Implantable Medical Devices

41

Table 2.3 Polymers used for implantable devices [26]

Polymers
Poly(tetrafluoroethylene)

Poly(dimethylsiloxane)
Polypropylene
Poly(ethylene terephthalate)
Polyamides (nylons)
Poly(ether urethane) (e.g. Pellethane)
Poly(ether urethane urea) (e.g. Biomer)
Low- and high-density polyethylene
Polysulfones
Polyvinylchloride
Poly(2-hydroxyethylmethacrylate)
Polymethylmethacrylate
Polyamides
Polyesters
Silicone
Hydrogels
Acrylic, nylon

2.3.2

Applications
Oxygenator membrane, vascular graft, catheter
coating, soft tissue augmentation, vascular
prostheses
Oxygenator membrane, tubing, shunt
Heart valve structures, sutures
Vascular grafts and prosthesis, shunt, sutures
Hemodialysis membrane
Percutaneous leads, catheters, tubings, intra-aortic
balloons
Artificial heart components, heart valve
Tubing; knee, hip, shoulder joints
Artificial heart components, heart valve
Tubing, blood bags
Catheter coating
Dental restorations, intraocular lenses, joint
replacement, e.g. bone cements
Sutures
Vascular prostheses, drug delivery systems like
drug-eluting stents, sutures
Soft tissue replacement, ophthalmology, finger joint
Ophthalmology, drug delivery systems
Tracheal tube

Polymers

Polymeric materials are rapidly replacing other material classes such as metals,
alloys and ceramics for use as biomaterials because of their versatility. Their applications range from facial prostheses to tracheal tubes, from kidney and liver parts to
heart components and from dentures to hip and knee joints. Various polymers used
for implantable medical devices are listed in Table 2.3.
Polymeric materials are generally classified into three different classes depending on their source: natural polymers, obtained from natural sources including both
plant and animal origin; synthetic polymers, based on totally synthetic sources; and
bio-inspired polymers which comprise materials synthesised to mimic a naturally
occurring polymer, but not necessarily identical to it. Natural polymers suffer from
various disadvantages such as possibility of antigenicity, possibility of microbial
contamination and source-to-source variability of properties. Hence, synthetic polymers have been the material of choice for implants because of their ease of production, availability and versatility of manipulation [27]. Bio-inspired polymers
promise innovative materials that have the potential to functionally replace diseased
or unavailable cell components, such as the extracellular matrix, which plays a
structural role in many organs and tissues [28].

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2.3.2.1

W. Khan et al.

Non-biodegradable Polymers

Ultrahigh molecular weight polyethylene (UHMWPE) was the first polymeric

material, used in medicine since the 1960s. UHMWPE is highly resistant to corrosive chemicals and has extremely low moisture absorption, very low coefficient
of friction, characteristic of self-lubrication and high resistance to abrasion.
UHMWPE emerged as a bearing material in many joint replacement devices. Tibial
bearings in knee arthroplasties and acetabular bearings in hip arthroplasties are the
most common uses of UHMWPE. Recently, it has been found that generation of
particulate debris from the articulating surface of this polymer is associated with
osteolysis and loosening of implants. Research has been carried out to address
these problems and highly cross-linked UHMWPE materials are clinically introduced. Another important medical advancement for UHMWPE in the past decade
has been the increase in use of fibres for sutures, where maximum strength and
minimum weight are required [25].
Polymethylmethacrylate (PMMA) is used extensively as bone cement, which is
primarily used to support the stems of total joint prostheses in the medullary cavity
of the bone. The primary purpose of the material is to fill the space between the
prostheses and bone to achieve more uniform stress distribution, and bone cements
do not serve as adhesives. PMMA is also used for replacement intraocular lenses in
the eye when the original lens is removed in the treatment of cataracts. PMMA
microspheres injected under the skin reduce wrinkles or scars permanently.
Polyetheretherketone, a thermoplastic polymer, is used as biomaterials for trauma,
orthopaedic and spinal implants [21].
The use of polyethylene terephthalate (PET) in medical devices has endured for
more than 50 years. Current medical applications of PET include implantable
sutures, surgical mesh, vascular grafts, sewing cuffs for heart valves and components for percutaneous access devices. The notable biological characteristics of PET
are biostability, promotion of tissue ingrowth, a well-characterised fibrotic response
and a long history of human implantation [29].

2.3.2.2

Biodegradable Polymers

For most applications, biodegradable materials offer advantages over other materials. The degradable nature of these materials allows for temporospatial clearance of
the material from the body, enabling the surrounding and/or ingrowth tissue to
autonomously restore its function over time after having benefited from the implant.
Synthetic biodegradable polymers offer the ability to control surface as well as
mechanical properties and degradation kinetics [28].
There are four major degradation mechanisms for polymers used in biomedical
devices: hydrolysis (reaction with water in tissues), oxidation (due to oxidants produced by tissues), enzymatic degradation and physical degradation (e.g. water
swelling and mechanical loading and wearing). Hydrolysis has been studied
extensively, especially for biodegradable polymers. Polyesters, polyorthoesters,
polyanhydrides, polycarbonates and polyamides are some of the polymers that are

2 Implantable Medical Devices

43

degraded by hydrolysis. Degradation of polyurethane material through oxidation is

observed in an implantable electrical insulation lead. Biological defence action is
also responsible for oxidative degradation, in which inflammatory cells generate
oxidative agents that diffuse into polymeric implants and degrade them. Enzymatic
degradation is also due to a defensive action against implanted foreign materials.
Collagens, polysaccharides (hyaluronic acids), some polyesters (e.g. polyhydroxyalkanoate, PHA), synthetic polycarbonates and proteins are mainly degraded due to
this type of reactions. Physical degradation is mostly due to mechanical friction
associated with motion under pressure, for example, the wearing of acetabular cups
of total hip replacements. Water swelling is another mechanism. This can be a problem if swollen polymers have significant changes in glass transition temperature,
geometry and mechanical properties such that the normal functions of the materials
are affected [30].
Potentially, devices made from bioresorbable polymers can overcome problems
associated with metal implants like stress protection, potential for corrosion, wear
and debris formation as well as the necessity of implant removal. Resorbable polymers have proven to be good materials for a range of devices in trauma surgery
[31]. Among resorbable polymers for implants, polyhydroxy acids occupy the
main position. These are mainly poly(l-lactide), poly(glycolide) and/or copolymers
based on l-lactide, l/dl-lactide, dl-lactide, glycolide, trimethylene carbonate and
caprolactone. These polymers are well known for their good biocompatibility, with
their degradation products being eliminated from the body by metabolic pathways.
Many reports have shown that the different PLA-based substrates do not present
toxicity since the cells were found to differentiate over the different polymers,
as demonstrated by the production of extracellular matrix components by various
cell types [32].
Polymers prepared from glycolic acid and lactic acids have found a multitude of
uses in the medical industry, beginning with biodegradable sutures first approved in
the 1960s. Since that time other medical devices, based on lactic and glycolic acid,
as well as other materials, including poly(dioxanone), poly(trimethylene carbonate)
copolymers and PCL homopolymers and copolymers, have been accepted for use as
medical devices. In addition to these approved devices, a great deal of research
continues on polyanhydrides, polyorthoesters and other materials [33].
Collagen has received increasing attention over the last years due to its excellent
biocompatibility, degradation into physiological end products and suitable interaction with cells and other macromolecules [34]. Resorbable forms of collagen have
been used for closure of grafts and extraction sites. Collagen-based membranes also
have been used in periodontal and implant therapy as barriers to prevent epithelial
migration and allow cells with regenerative capacity to repopulate the defect area
[35]. Tissue-based collagen devices are mostly used for cardiovascular applications
in the form of heart valves, vascular prostheses [36].
Polymer coatings such as silicone rubber, PTFE, Parylene and epoxy were used
to encapsulate the implantable devices. However, these materials are biocompatible; they have limited abilities to protect the device from water ingress. Polyetherbased polyurethane elastomers are currently used in a variety of blood- and
tissue-contacting devices in biomedical applications due to their biocompatibility

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W. Khan et al.

and stability in biological environment together with their superior processability.

Despite their excellent mechanical properties and biocompatibility, the chemical
structure and morphology of polyurethanes make them relatively permeable to
gases and water [37].

2.3.3

Ceramics and Composites

Restorative materials in dentistry such as crowns, cements and dentures are made up
of ceramic materials. The poor fracture toughness of ceramics severely limits their
use for load-bearing applications. They are generally used to replace or fix hard connective tissue, such as the bone [22]. The bone itself is a composite, comprising an
organic phase and a ceramic phase. This ceramic phase is predominantly calcium
hydroxyapatite with a Ca/P ratio of 1.67. Thus, synthetic calcium hydroxyapatite is
a good candidate for a successful biomaterial. Several dental and orthopaedic metal
implants are coated with hydroxyapatite to ensure long-term fixation in bone [21].
Zirconium dioxide or zirconia ceramics (ZrO2), a bioinert nonresorbable metal
oxide, is being recognised for its high strength, toughness and surface finish. It is
used to manufacture femoral heads for total hip replacements and this material is
potentially suitable for the highly loaded environments found in joint replacement.
A ceramic that is used in load-bearing applications is high-purity alumina. It is used
as the bearing surface in total hip prostheses. The material is characterised by
its excellent biocompatibility and high strength, hardness and fracture resistance.
A class of glassy bioactive ceramics upon implantation undergo a modification of
their surface and form a layer of a very bioactive form of hydroxyapatite. As new
bone is formed in opposition to this layer, it forms a very strong bond such that the
mechanical integrity of the bond can exceed that of bone. Widescale use of these
materials has been limited due to their brittle nature [25].
The most successful composite biomaterials are used in the field of dentistry as
restorative materials or dental cements. Although carboncarbon and carbonreinforced polymer composites are of great interest for bone repair and joint replacement because of their low elastic modulus levels, these materials have not displayed
a combination of mechanical and biological properties appropriate to these applications. Composite materials are, however, used extensively for prosthetic limbs,
where their combination of low density/weight and high strength makes them ideal
materials for such applications.

2.3.4

Drugs and Other Biomolecules

The coated implant can be viewed as a drug/medical device combination product

which represents an emerging new trend in therapeutics. Combination products
facilitating localised drug delivery have already been used in a variety of applications from cardiovascular diseases to diabetes. Drug and device combinations can

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45

be designed to increase the performance and life time of currently used implants
resulting in improved patient life quality [38]. Drug-coated implants function as a
semipermeable compartment that holds the drug while permitting passage of preferred molecules in a controlled manner. Drug-eluting stents are good examples of
such devices [4, 39, 40].
Various immunosuppressive drugs (sirolimus, everolimus, tacrolimus, ABT578), antiproliferative drugs (paclitaxel, actinomycin, angiopeptin, etc.), antimigratory drugs (batimastat) and gene therapeutic reagents (antisense and siRNA,
vascular endothelial growth factor, endothelial nitric oxide synthase (eNOS and
related genes)) have been combined with stents and investigated for their local
release and antirestenotic effects. FDAs approval of Cordis CYPHER sirolimuseluting stent (2003) opened the gate for adapting new technology combining both
device and pharmaceutical designs [41].

2.4

Requirements of Implantable Devices

2.4.1

Mechanical Properties

Elasticity, yield strength, ductility, toughness, creep, ultimate strength, fatigue

strength, hardness and wear resistance are some of the important mechanical properties of materials used in implantable medical devices.

2.4.1.1

Yield Strength

The yield strength determines the load-bearing capability of the implant. For example, in the case of TJR surgeries where a high load-bearing capability of the implant
is essential, one ideally needs an appropriately high yield strength value of the alloy.
Thus, the orthopaedic alloys should have a sufficiently high yield strength value
with adequate ductility (defined by percentage elongation or percentage reduction
of area in a standard tensile test) [42].

2.4.1.2

Elastic Modulus

There is always a concern for the relatively higher modulus of the implant compared to that of the bone (_1040 GPa, or 1.56 _106 psi) [3]. Long-term experiences indicate that insufficient load transfer from the artificial implant to the
adjacent remodelling bone may result in bone reabsorption and eventual loosening
of the prosthetic device [43]. It has been seen that when the tensile/compressive
load or the bending moment to which the living bone is exposed is reduced,
decreased bone thickness, bone mass loss and increased osteoporosis occur. This is
termed the stress shielding effect, caused by the difference in flexibility and

46

W. Khan et al.

stiffness, which is partly dependent on the elastic moduli difference between the
natural bone and the implant material [44]. Any reduction in the stiffness of the
implant by using a lower-modulus material would definitely enhance the stress
redistribution to the adjacent bone tissues, thus minimising stress shielding and
eventually prolonging the device lifetime [3].

2.4.1.3

Fatigue

Variable fatigue resistance of the metallic implants is also a cause of concern while
developing an alloy. The orthopaedic implants undergo cyclic loading during body
motion, resulting in alternating plastic deformation of microscopically small zones
of stress concentration produced by notches and microstructural inhomogeneities.
Standard fatigue tests include tension/compression, bending, torsion and rotationbending fatigue testing [3].

2.4.2

Corrosion and Biocompatibility

Degree of success of an implant is determined by reactions at the interface between

an implant and the environment of the body. In the case of orthopaedic implants,
one of the potentially important aspects of this interfacial reaction concerns metallic
corrosion. The metals and alloys used as surgical implants achieve passivity by the
presence of a protective surface passive film. This film inhibits corrosion and keeps
current flow and the release of corrosion products at a very low level, i.e. all the
implantable materials undergo corrosion at some finite rate due to complex corrosive environment of the body, while in use [45].
Metallic implant degradation results from both electrochemical dissolution and
wear but most frequently occurs through a synergistic combination of the two [46].
Electrochemical corrosion processes include both generalised dissolution uniformly
affecting an entire surface and localised areas of a component [47]. Locally these
areas tend to be at both identifiable areas relatively shielded from the environment
(e.g. crevice corrosion) and at random sites on the surface (e.g. pitting corrosion).
In the past, these electrochemical and other mechanical processes have interacted to
cause premature structural failure and accelerated metal release (e.g. stress corrosion cracking, corrosion fatigue and fretting corrosion) [48].
The only way to reduce the corrosion of surgical implants is selecting an appropriate alloy with improved surface properties by addition of alloying elements,
which improve the nature, composition and stability of the passive film; homogenisation treatment to dissolve the second-phase precipitates; production of cleaner
varieties of steels using advanced steel-making processes in order to have control
over inclusions; avoiding improper heat treatment; and fabrication in order to eliminate the formation of second phases especially at grain boundaries. Also, the nature,
composition and chemical stability of passive films with superior corrosion

2 Implantable Medical Devices

47

resistance can be produced through surface treatment by ion beams. Many of the
cases of corrosion could be avoided by improvements in materials selection, implant
design, quality control, materials handling and education [45].
According to Williams in 2008, biocompatibility refers to the ability of a biomaterial to perform its desired function with respect to a medical therapy, without
eliciting any undesirable local or systemic effects in the recipient or beneficiary of
that therapy but generating the most appropriate beneficial cellular or tissue response
in that specific situation and optimising the clinically relevant performance of that
therapy [49]. Biocompatibility studies on an implantable device require complex
experiments both in vitro and in vivo in order to test the local and systemic effects
of the material on culture cells, tissue sections and the whole body [50].
In vitro assessment of tissue compatibility usually involves performing cell cultures for a wide variety of materials used in medical devices. Direct contact, agar
diffusion and elution are the three different cell culture assays used for in vitro
study. In all the tests, experimental variables such as cell type (usually l-929 mouse
fibroblast), number of cells, duration of exposure and test sample size are kept constant [51]. Positive and negative controls are often used during the assay test to
determine the viability of the test. In all cases, the amount of affected or dead cells
in each assay provides a measure of the cytotoxicity and biocompatibility of the
biomaterials. Cell adhesion, cell spreading, cell migration, cell proliferation and cell
function are some of the key parameters that can be investigated individually in
these assays [52]. In vivo assessment of tissue compatibility tests are performed to
determine the biocompatibility of a prosthetic device and also to assess whether the
device is performing according to expectations without causing harm to the patient.
Some tests, such as toxicity, carcinogenicity, sensitisation and irritation, determine
if the leachable products of the medical device affect the tissues near or far from the
implant site. Other tests, such as implantation and biodegradation, study the postsurgery changes in the implant material itself and their ensuing effect on the body.
For conducting the actual in vivo tests, animal models (sheep, pig, rat) are usually
selected after weighing the advantages and disadvantages for human clinical applications [42].

2.4.3

Sterilisation

Infection is a major problem associated with implantable devices, and a further

complication is that organisms of relatively low virulence are frequently found to be
pathogenic when they contaminate the bioimplant. Further, little is known about the
effect of a prosthetic device on either the host immune response or the inflammatory
action of the tissue with which the prosthesis interfaces [53]. Composition of the
device and its function, the location, the length of time the device is in place and the
underlying condition of the patient are some of the factors affecting the pathogenesis of such infections and the relative rate of infection [54]. The same implant
located in different body areas can be associated with different flora, potentially

48

W. Khan et al.

Table 2.4 Different methods used for sterilisation of implantable medical devices [53]
Method
Principle
Steam
Saturated steam in the
sterilisation
range of 121134 C

Advantages
Sterilises penetrable
materials and
exposable
surfaces
Dry heat
Carried out in electrically
Ability to penetrate
sterilisation
heated ovens
solids
at 160180 C
Lack of corrosion
in case of
non-stainless
steel metals
Ethylene oxide Biocidal activity is achieved Suitable for heatat 30 % humidity, 45 C
sensitive
temperature levels with
implants
>450 mg/l gas
concentration

Radiation
Primary biocidal action is
High-energy
sterilisation
via aqueous free radical
irradiation
formation following the
sterilisation
primary physical
interaction of the ionising
radiation with the
biological material

Disadvantages
Microcavitation in case of
hydrophilic polymers
Altered biocompatibility
of heparinised surfaces
Rubbers, plastic, etc. do
not withstand high
temperature

EO residues after
sterilisation cause:
Anaphylactoid reactions
in dialysis patients
Serious tissue reactions
in pump oxygenators
Mutagenicity and
carcinogenicity
Degradation and/or
cross-linking of
polymers
Gas evolution and free
radical formation from
polymers

different host defence mechanisms and other alterations in milieu that may alter the
potential development of prosthesis-associated infection. Implants can also alter the
host immune response, through alterations of phagocytic capacity, inflammatory
response or immunoglobulin synthesis [55]. Sterilisation of implantable devices is
carried out to eliminate infecting microorganisms upon the device. Various sterilisation procedures used for implants are listed in Table 2.4 along with their advantages
and disadvantages.

2.5
2.5.1

Applications
Drug Delivery and Scaffolds

One of the fastest growing areas for implant applications is for devices for
controlled and targeted delivery of drugs. Combinations of drug and device are
predicated on the principle of local controlled drug delivery from an implanted

2 Implantable Medical Devices

49

prosthetic device whose primary purpose is functional or structural replacement of

host tissue. Optimal dual functions (i.e. drug release and prosthetic performance)
are ideally coordinated and designed to work in tandem. Hence, drug release properties from the device are not simply adjunct to device implantation and must be
thoroughly understood. Drug release strategies from implantable devices are frequently considered to address thrombosis, osteomyelitis, periodontitis, biomedical
device-related infections and other microbial pathologies or inflammatory complications [41].
Currently, there are various methods available and being used for drugimplant
combinations. While polymeric coatings are one of the best recognised techniques,
depending on the application, there are other methods currently available and nanoporous coatings are one of them. The nanoporous ceramic templates can be fabricated directly on the currently available implants or stents [4]. Drug loading for the
nanoporous templates generally is performed through capillary action by either
immersing the templates in the concentrated drug solution or dropping the solution
slowly on the template surfaces [56]. Different techniques have been used to increase
and accelerate the intake of the drug, including surface enhancement, sonication or
solution aids [57]. One of the unique features of these nanoporous coatings is the
ability to precisely control the surface properties. By varying the pore size, distribution and density, drug loading and release can be altered. Surface charges of these
pores can also be modified to hydrophobic or hydrophilic to accommodate variety
of drug molecules. Additionally, through suitable surface modification the release
kinetics of the drug molecules can be altered [4].
Many exciting new opportunities exist in the application of microfabricated drug
delivery devices to medicine and biology. Microfabricated devices are poised to
revolutionise drug delivery. They offer new methods to deliver compounds in a targeted manner, at the desired rate, and are compact to allow minimally invasive
placement [58]. Micro- and nano-electromechanical systems (MEMS or NEMS)based polymeric and electromechanical delivery devices create totally new drug
delivery paradigms. MEMS technology has been used to construct microreservoirs,
micropumps, nanoporous membranes, nanoparticles, valves, sensors and other
structures using biocompatible materials appropriate for drug administration [59].
Using NEMS, complex mechanical nanostructures can be built with lateral dimensions as small as tens of nanometers. By incorporating transducers, control and
measurement functions can be built into these systems [60]. A biodegradable polymer chip version of an implantable multireservoir drug delivery device incorporates
an array of reservoirs capped with resorbable membranes that may differ from other
membranes in the array by thickness or chemical composition. The interior of each
reservoir contains drug formulation(s). An advantage of biodegradable polymerbased systems compared to microchip-based systems is the elimination of a requirement for a second surgery to remove the device. In addition, the lack of electronics
reduces any size restrictions in terms of device manufacture. Such systems are simpler but will not deliver reservoir contents with as much precision as the analogous
microelectronic devices [61].

50

W. Khan et al.

Drug-eluting stents are among the most widely known combination products.
Micromachining technology allowed bare-metal stents to be manufactured that had
the physical capability of propping open occluded vessels. Coating the stent with a
drug-containing polymer resulted in combination products featuring localised drug
release capability in addition to the mechanical action of the stent. Next-generation
drug-eluting stents incorporate reservoir-based drug containment on the stent surface, with release properties determined by polymer composition and layer thickness [62].
In case of orthopaedic device-based drug delivery, osteo-inductive molecules as
well as biologically derived growth factors, anti-osteoporotic agents and osteosynthetic genetic materials (DNA, siRNA) to bone injury sites are successfully
delivered [63]. Osteo-precursor cell-based local delivery is reported for bone engineering [64]. These biotechnology approaches seek to accelerate and enhance bone
defect healing and bone-implant stabilisation through local release of cells and
mitogenic and morphogenic agents. One commonly used infection management
method with orthopaedic implants utilises antibiotics loaded into clinically ubiquitous bone cement, polymethylmethacrylate beads. These non-biodegradable polymer cements have been employed clinically to prevent or treat osteomyelitis in
various forms [65].
One of the key components in successful tissue engineering is the production of
the correct scaffold using biomaterials. An ideal scaffold should provide cells not
only with a structural framework but also with the appropriate mechanical and biochemical conditions so that these cells can proliferate and produce extracellular
matrix to form tissue. Areas of research in tissue engineering include the repair or
regeneration of the skin, blood vessels, nerves, liver, bone and articular cartilage.
PLA and PGA are prime candidates for such scaffolds because they are biocompatible, provide the appropriate mechanical environment, can be easily fabricated and,
moreover, are biodegradable. Collagen sponges are also under investigation [21].
Various FDA-approved implantable devices are listed in Table 2.5.

2.5.2

Structural and Mechanical Support

Currently, one of the main achievements in the field of arthroplasty is total joint
replacement, where the entire load-bearing joint (mainly in the knee, hip or shoulder) is replaced surgically by ceramic, metal or polymeric artificial materials. Bone
replacement, fracture fixation, dental implants, dental restorations, bone plates and
orthodontic wires are some of the medical devices that provide structural and
mechanical support (Table 2.6).

The main portion of the graft is made

of a plastic tube supported partially
by polymer-filled rings and partially
by a metallic stent
Thermosensitive polymer (poloxamer)

OVATION Abdominal
Stent Graft System

LeGoo

Propel

ION Paclitaxel-Eluting
Coronary Stent System

Gel-One

Synvisc-One (hylan GF-20)

Medtronic Attain StarFix

Epicel cultured epidermal

autograft (CEA)

2.

3.

4.

5.

6.

7.

8.

9.

Sheets of autologous keratinocytes

(skin cells)

The implant contains the active

ingredient mometasone furoate,
a steroid which suppresses inflammation
in the area around the implant
Expandable, stainless steel tube with
paclitaxel contained within a thin
polymer coating surface
Hyaluronate hydrogel produced from
chicken combs, in a phosphatebuffered saline solution
Elastoviscous high molecular weight
fluid containing hylan polymers
Surgically implanted insulated wire that is
designed to be used as a part
of a biventricular pacemaker system

Polymer/drug
Everolimus-eluting platinum chromium stent

The other end of the lead connects to an

implanted biventricular pacemaker or
implantable cardioverter-defibrillator, so
signals and electrical impulses can be sent
between that device and the left ventricle
Cultured epidermal autografts, or skin grafts,
used to replace the epidermal or top layer
of skin on severely burned patients

Treatment of osteoarthritis

Treatment of osteoarthritis

Paclitaxel-Eluting Coronary Stent

Injected into a blood vessel to temporarily

plug a blood vessel and stop blood flow
Temporary, self-absorbing implant designed
to keep the spaces within and around the
sinuses open following sinus surgery

Used to treat abdominal aortic aneurysms

during endovascular repair

Purpose/use
Coronary stent

Table 2.5 FDA-approved implantable medical devices intended for localised drug delivery and functional support

S.No. Device
1.
PROMUS Element Plus

[70]

[69]

[68]

[67]

References
[66]

Genzyme Biosurgery

Medtronic, Inc.

Genzyme Biosurgery

(continued)

[74]

[73]

[72]

Seikagaku Corporation [71]

Boston Scientific
Corporation

Intersect ENT

Pluromed, Inc.

Manufacturer
Boston Scientific
Corporation
Trivascular, Inc.

INFUSE Bone Graft

INFUSE Bone Graft is used to fill space

where the bone is needed in order
to place endosseous dental implants

Polymer/drug

Purpose/use

Manufacturer

Endosseous dental implants are inserted

Medtronic Sofamor
in the jaw and have an exposed head that
Danek
can be used to secure dental devices
like a crown, fixed bridge or dentures
11.
Onyx Liquid Embolic
The Onyx LES is an artificial material
This material is used to block the flow
Micro Therapeutics,
System (LES)
used to block blood flow in the treatment
of blood before surgical treatment
Inc.
of malformed blood vessels in the brain
of the malformed vessels
Y-shaped stent graft made out of a fabric
Endovascular graft and used to treat an
12.
Endologix PowerLink
Endologix, Inc.
System
tube of synthetic material called ePTFE
abdominal aortic aneurysm during a
surgical procedure called endovascular
repair
13.
Nuflexxa (Sodium
1 % sodium hyaluronate solution
Injected into knee joints to treat pain from
Savient PharmacHyaluronate)
osteoarthritis of the knee
euticals, Inc.
http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/DeviceApprovalsandClearances/Recently-ApprovedDevices/ucm286493.htm

10.

S.No. Device

Table 2.5 (continued)

[78]

[77]

[76]

[75]

References

Edwards SAPIEN
Transcatheter Heart
Valve
Restylane
Injectable Gel
EUFLEXXA

St. Jude Medical

Trifecta Valve

ProGEL Pleural
Air Leak Sealant

Gel-One

Sculptra Aesthetic

2.

5.

6.

7.

8.

4.

3.

Device
Belotero Balance

S.No.
1.

Cow tissue attached to a

stainless steel mesh frame
with a polyester wrap
Restylane is a transparent
hyaluronic acid gel
Hyaluronate hydrogel in a phosphatebuffered saline solution
The valve leaflets are manufactured using
bovine pericardial tissue.
A polyester-covered titanium stent
supports the bovine
pericardial tissue
Made of human serum albumin
and a polyethylene glycol (PEG)
cross-linker that forms a clear flexible gel
on mixing
Hyaluronate hydrogel produced from
chicken combs, in a phosphate-buffered
saline solution
Sculptra Aesthetic is an implant
of poly-l-lactic acid (PLLA)
microparticles

Polymer
Hyaluronic acid gel

It is injected into the facial tissue

to correct shallow to deep smile
lines (nasolabial fold), contour
deficiencies and other facial
wrinkles

Surgical sealant, sprayed or

painted on the lung tissue.
The ProGEL forms on the
lung tissue by chemical reaction
Treatment of osteoarthritis

Injected into a patients lips

to increase their size
Used to relieve pain in the knee
due to osteoarthritis
The Trifecta valve is a three-leaflet
stented pericardial valve
designed for supra-annular
placement in the aortic position

Purpose/use
Injected into facial tissue
to smooth wrinkles and folds
Heart valve

Table 2.6 FDA-approved implantable medical devices used for structural and mechanical support

Sanofi-Aventis U.S.

Seikagaku Corporation

NeoMend, Inc.

[82]

Ferring Pharmaceuticals,
Inc.
St. Jude Medical

(continued)

[85]

[71]

[84]

[83]

[81]

[80]

References
[79]

Aesthetics Holdings, Inc

Edwards Lifesciences

Manufacturer
Merz Pharmaceuticals

Mitroflow Aortic
Pericardial Heart
Valve

Cosmetic Tissue
Augmentation
Product

Radiesse

10.

11.

12.

Cosmetic Tissue Augmentation

Product (CTA) is a transparent
hyaluronic acid gel with 0.3 %
lidocaine that is injected into
facial tissue
Radiesse is an injectable calcium
hydroxyapatite implant in the
form of a gel

Consists of a single piece of bovine

pericardium that is preserved with
glutaraldehyde and sewn onto a
polyester covered polymer stent

Collagen Filler

Polymer
Injected into the inner layers of
facial skin (mid to deep dermis)
in order to correct moderate to
deep facial wrinkles and folds
The Mitroflow Aortic Pericardial
Heart Valve is intended for the
replacement of diseased,
damaged or malfunctioning
native or prosthetic
aortic valves
CTA works by temporarily adding
volume to facial tissue and
restoring a smoother appearance
to the face

Purpose/use

Anika Therapeutics, Inc.

CarboMedics, Inc.

ColBar LifeScience Ltd.

Manufacturer

Radiesse works by temporarily

BioForm Medical, Inc.
adding volume to facial tissue
and restoring a smoother
appearance to the face
13.
Inamed Silicone-Filled
Implant is a silicone shell filled
The breast implant is surgically
Allergan
Breast Implants
with silicone gel
implanted either under breast
tissue or under the chest muscle
Contains small
14.
ArteFill
Filler that is injected into the
Artes Medical, Inc.
polymethylmethacrylate beads,
nasolabial folds around the
collagen and lidocaine
mouth to smooth these wrinkles
15.
Juvederm Gel
Hyaluronic acid gel
Injected into the middle layer
Inamed Corporation
Implants
of skin (mid to deep dermis)
to temporarily correct moderate
to severe facial wrinkles
and folds
http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/DeviceApprovalsandClearances/Recently-ApprovedDevices/ucm286493.htm

EVOLENCE
Collagen Filler

9.

Device

Table 2.6 (continued)

S.No.

[92]

[91]

[90]

[89]

[88]

[87]

[86]

References

2 Implantable Medical Devices

2.6

55

Conclusion

Medical devices are now a pervasive part of modern medical care. The medical
development in terms of implantable devices has brought about the robust change in
the life of the people (as offered by the cosmetic treatment, dentist, face and cardiology devices). Medical devices have extended the ability of physicians to diagnose
and treat diseases, making great contributions to health and quality of life. The
approach to quality of devices has depended largely on regulation. The critical
nature of medical devices has caused them to come under stringent regulations.
Clearance to market devices in the USA is granted only after the Food and Drug
Administration (FDA) has determined through its classification and review procedure that there is reasonable assurance of the safety and effectiveness of the device.
Such regulatory requirements are necessary and appropriate. A rigorous but responsive and responsible regulatory process helps to ensure that new medical technologies represent the state of the art, have the real potential to do good as demonstrated
in scientifically grounded studies and reach patients promptly. Despite the enormous contribution medical devices have made to the public health, there is a fear of
the possibility of liability exposure in the event of device malfunction or failure. Its
influence is growing and is having a chilling effect on innovation. It also damages
global competitiveness and increases health care costs directly and indirectly.
Ironically, the shadow of product liability may actually be keeping better performing products from the market rather than being a force for improvement.

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