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Chapter 9 discusses the critical process of biocompatible material selection in biomedical product design, emphasizing the importance of material properties, manufacturing processes, and biocompatibility requirements. The chapter outlines a systematic design flow that includes market research, concept formulation, embodiment, and detailed design, highlighting the need for thorough evaluation and risk management in material selection. Additionally, it addresses the degradation of materials and its impact on the performance and reliability of implanted devices, stressing the significance of proper material characterization and testing.
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0% found this document useful (0 votes)
8 viewsDesign Chapter
Chapter 9 discusses the critical process of biocompatible material selection in biomedical product design, emphasizing the importance of material properties, manufacturing processes, and biocompatibility requirements. The chapter outlines a systematic design flow that includes market research, concept formulation, embodiment, and detailed design, highlighting the need for thorough evaluation and risk management in material selection. Additionally, it addresses the degradation of materials and its impact on the performance and reliability of implanted devices, stressing the significance of proper material characterization and testing.
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chukwumablessing031Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
Available Formats
Download as PDF or read online on Scribd
/ 24
Chapter 9
Biocompatible Material Selection
Abstract Material selection under the guidance of the general principles must be
considered from the material's own properties and the available manufacturing
processes. Manufacturing designers should consider a broad range of factors affect.
ing the requirements and feasible options for the optimal functions, biocompatibility,
and manufacturing outcomes of the target biomedical or healthcare products. Some-
times, relationships of the design factors can be transformed as a combined expres.
sion called the material performance index.
9.1 Product Design and Material Selection
9.1.1 General Product Design Flow
Material selection is a critical step in the process of designing any product, including
biomedical devices, In the context of product design, the main goal of material
selection is to minimize cost and production time while mecting product perfor-
‘mance goals. Systematic selection of the best material for a given application begins
‘with the properties and costs of candidate materials, For example, a thermal blanket
‘must have low thermal conductivity to minimize heat transfer for a given tempera-
ture difference. An incorrect or inappropriate selection may result in poor results. An
incorrectly chosen material can lead not only to failure of the part but also to
unnecessary life eycle cost. A poorly chosen material ean add to manufacturing
cost and unnecessarily increase the cost of the part. Besides, the properties of the
‘material can be enhanced or reduced by different material processes, and these may
affect the resultant product performance.
Material selection under the guidance of the general principles must be consid
cred from the material's own properties and the available manufacturing processes,
Material selection not only acts as a downstream step after product design but also
plays an important role in the feedback loop of product refinement and innovation,
Formulation of technical specifications for a biomedical device can be achieved
through a breakdown of the complete device into assemblies and components,
followed by considering the requirements for each of them, Material and process
© Springer Nature Switzerland AG 2019 2a
R. HW. Lam, W, Chen, Biomedical Devices,
Inipsdo.org10,10077978-3-030-24237-4.9 2a 9 Biocompatible Material Selection
Market need
Define spciicaion
Determine funtion strvture
Seek working pincpies
Evanate and slac sonconts
"Analyse components deta
Slee processing route aaa
‘Opimizeperomance and cost
Prepare dots drawings
Product
spectioaion [~C tert >
Fig. 9.1 ‘The general product design flow. The design proceeds from an ideniiation and
clarification of task through concept, embodiment, and detailed analysis to a product specification
selections can first be decided at the component level and then be integrated with
some further refinements as more comprehensive requirements for the device arc
decided. The general product design flow contains four main stages (Fig. 9.1):
‘+ Market need: Market research should be first carried out with the purpose of
investigation, especially targeted market research, The contents of a market
investigation should be closely related to product design. There are many
‘methods of market rescarch, such as on-the-spot investigation, online consulta-
tion, and consulting materials. For instance, home-based care and health moni-
toring devices need to pay closer attention to their product appearance and user-
Iriendliness. These devices, used by patients or family members without direct
clinical supervision, may require extra concerns, such as improved ergonomics.
‘The use of color, special notice effects, and textures can help patients intuitively
understand and follow proper usage parameters. Lightweight materials without
‘compromised strength or durability can increase the device’s portability,
+ Concept formulation: This is defining the target specifications of a product.
Besides, it is also required to discuss the functional structure of a product.
Secking working principles is also needed during this stage. The final step is to
evaluate and select concepts of the product.
+ Embodiment: It is suggested to draft multiple possible layouts, geometric fea-
tures, and other brief descriptions of the product which all fultill the basic product
specilications. Based on these brief descriptions, we may further model the 9.1 Product Design and Material Selection 245
assemblies and define the sub-parts and components. Itis expected that there are
‘multiple options and designs for the targeted product. Hence, we then need to
evaluate and select the “best” brief design of the product.
+ Detailed design: After the above three steps, the components can be analyzed in
detail in order to finalize the component shapes, the materials to be used, and the
chosen manufacturing processes. As multiple matcrial and manufacturing pro-
ccesses can be involved in producing one component, we need to arrange and
configure the processing route (including assembly of all the components) and
‘operation parameters in order to optimize performance and minimize the produc-
tion cost and time. After all the product and process details are confirmed, detailed
drawings of each component of the product can also be prepared,
TThe process from the concept formulation to the detailed design can be integra-
tive. Once the detailed design is ready, it can be further examined on whether or not
ittcan meet the target product specifications. Ifthere are any necessary modifications
realized at this stage, the product design process may need to be revised from the
concept formulation stage.
9.1.2 Design Flow of Biomedical Products
For designing biomedical products, designers need to consider both the material
property and biocompatibility requirements; a simplified decision flow is shown in
Fig. 9.2. First, we need to ensure the chosen material can fultill the physical
requirements of a product component following the product design process. Fur-
thermore, we need also to check whether the material is biocompatible. Biocompat.
ibility is the capability of a material to function in an in vivo environment for an
acceptable period of time with no detrimental effect or only an acceptable level of
effects on the host If there is no related record available, we will need to test whether
fr not the material would initiate any effects at the expected implant site. In
particular, since the immune response and regenerative functions of the body are
very complicated, it is not adequate to deseribe the biocompatibility of a single
‘material in relation to a single cell type or tissue. We would need to go through a
series of animal experiments and subsequent clinical trials to determine the biocom-
patibility of the material
= Pe et i te
Same
Fig. 9.2. Decision tee for biomedical device development 246 9 Biocompatible Material Selection
Establishing the biocompatibility of medical devices and their materials is of key
importance in assuring product safety. Central othe issue of biocompatibility is the
role of chemistry and material characterization. Presently, the biological evaluation
cof medical devices is governed by the set of standards developed by ISO and known
as the ISO 10933 series of standards. This document establishes the need for
toxicological risk assessment based on chemical and material characterization
prior to initiating any biological testing.
Although regulatory bodies cemtify the safety and efficacy of finished medical
devices rather than their component materials, a detailed master access file for a
certain material can often help smooth the oad to device approval. A manufacturing
partner with a dedicated regulatory practice can help device companies identify
redical-grade plastics, elastomers, and composites that meet US Food and Drug
Administration (FDA) and United States Pharmacopeia (USP) Class VI require
‘ments as well as those for international regulations.
“Materials characterization forms the basis for understanding the composition of a
redial device material and its potential to have an adverse biological effect when
the device is put into clinical use. Materials selection and risk analysis are integral
components of the design process for medical devices and play critical roles in
evaluating biological safety. Just as important as the testing, the biological safety
evaluation plan should be designed and performed to demonstrate the achievement
of special criteria for safety. Clearly, the process presented in ISO 10933-1, 10933-
18, and 10933-17 may aid inthe selection of optimal materials and in the control of
the uniformity of those materials throughout the lifetime of the deviee, IF appropriate
care is taken to minimize critical controlling factors, in vitro materials testing can
frequently accurately predict clinical outcomes.
‘The evaluation of risk management includes identification ofall hazards and the
estimation of associated risk. A major component in hazard identification is mate-
rials characterization. These following steps can be identiie:
1, Define and characterize each material, including suitable alternative materials.
2. Identify hazards in materials, additives, processing, and cleaning aids.
3. Estimate exposure (total or clinically available amounts).
4, Review toxicology and other biological safety data (published and available)
‘The risk management approach emphasizes that conducting animal testing for
risk evolution should only be considered after all altemative courses of action
(review of prior knowledge, chemical characterization, in vitro evolution) have
been established. Several clauses and subclauses in ISO 10933-1 ask the user to
conduct chemical characterization of the device undergoing biological evaluation.
‘A variety of techniques are available for performing chemical and materials
characterization, The tests may be carried out directly on material samples or on
‘material extracts prepared under specilied conditions. These tests, which have
evolved over many years, arc relevant, sensitive, rapid, and inexpensive, yet they
provide extremely valuable information to establish material safety and biocompat-
ibility. The extent to which a material needs to be characterized depends upon the
type of material, the end use of the device, and the function of the material within the 9.2. Considerations of Material Characteristics 2
Table 91 Categorization of medical devices
‘Nature of contact and Duration Degree of
tissue type of contact _ Types of devices characterization
‘Surface Timited | Exam gloves, taps, blood pressure | Minimal
‘Skin ‘uff dental dams, endoscopes
‘Mucous membranes
External communication | Prolonged | Dialysis, cardiopulmonary bypass |Tntermediate
Blood, inicect
Implant Permanent Shunts or grafts onhopeic implants | High
Blood, dret tissue
device. The more critical the role of the device and the more important the properties
of its materials are to device performance, the more detailed the characterization
program should be. Table 9.1 ists the various categories of devices defined in ISO
1093-18 and the proposed degree of characterization necessary
9.2 Considerations of Material Characteristics
9.2.1 Basic Factors
Manufacturing designers should consider a broad range of factors affecting the
roquirements and feasible options for the optimal functions, biocompatibility, and
‘manufacturing outcomes of the target biomedical or healthcare products. Biocom-
patibility is ultimately a function of a completed device, so it encompasses all ofits
‘components, assembly processes, and overall design. However, thoughtful material
selection can help ensure the overall biocompatibility of a finished product. Even
when materials incorporated into a medical device have been assessed for their
biocompatibility, new risks can be introduced through manufacturing and postpro-
duction processes that can have an adverse effect on the device. Properly clean
assembly and hygiene processes help to lower these risks. Here, we briefly exem-
plify other common factors in most product design processes.
Generally speaking, material cost is acritical aspect of any medical device. In the
broader sense, the manufacturing designers should look beyond the simple expenses
of raw materials and adopted processes in order to assess a device's true life cycle
costs. The labor wage or the tool life during assembly should also be taken into
consideration. Excluded from the material cost are all indirect materials, such as
cleaning supplies used in the production process. The cost of labor to produce the
product is separate from this cost. The total cost of a product and its eventual sale
price are arrived at by combining the material cost with the cost of labor. Addition-
ally, the costs have time factors. Different materials can cause costs to increase or
decrease over time. It is important to consider how each candidate material can add 248 9 Biocompatible Material Selection
fr reduce the unit cost of a device throughout the full life eycle. If necessary,
‘manufacturing processes should also be tweaked to reduce the required energy and
cost. However, sometimes a more expensive, higher performing material can save
‘money in the Tong run,
‘The material selection process is to match performance capabilities fulfilling the
device specications. Performance capabilites can range from mechanical proper-
ties, such as strength, flexural modulus, and high-temperature resistance, to chemical
resistance, particularly exposure to harsh antibacterial cleaners, Furthermore, the
sustainability of medical devices comes into play primarily during design and
‘manufacturing as they cannot be easily disposed of or replaced once implanted into
‘a human body. In the design phase, sustainability considerations include strategies
such as the use of lower-dlensity and more biocompatible materials. They also include
the demands of common usage scenarios, including resistance to breaking/cracking
from impact. Some materials are inherently strong, flexible, or chemically resistant,
while others ean be enhanced with additives or reinforced with glass fiber.
‘Apparently, the material properties discussed in Chaps. 2, 3, 4, and 5 are major
concerns as they directly determine whether the product is functional and biocom.
patible. Taking an artificial joint product as an example, a good artificial joint material
is necessary. For the weight-bearing joints the related material ought to bear stress of|
700 MPa with a safety factor of 10 because the ultimate tensile strength of bone is
about 70 MPa. Elastic modulus is clinically important because it indicates that the
selected biomaterial has similar deformable properties with the material itis going to
replace. (A number of methods are available for determining the tensile strength of
‘materials, such as the bending flexural test, the biaxial fexural strength test, and the
Weibull analysis.) These force bearing materials require high elastic moduli with low
deflection, As the elastic modulus of a material increases, fracture resistance
decreases. It is desirable for the biomaterial clastic modulus to be similar to bone.
‘This is because if it is greater than bone’s elastic modulus, then load will be bome by
the material only, while the load is borne by bone only if it is less than the material,
‘The fracture strength, which is the stress at which a specimen begins to crack,
should also be analyzed. Strength of a biomaterial is an important mechanical
property. In particular, bioceramics are often britle. Once cracks are formed on a
‘material body, the cracks can then easily propagate when the material is subject to a
much lower loading stress than the material strength, This importance is clear for
bioceramics which have higher ductility on top of their high strength. For example,
there are a number of other ways that cracks can be produced in bioceramies, such as
thermal sintering and heating,
In addition, fatigue is also an important parameter for biomaterials because cyclic
load can be applied during their life cycle in a human body with repeating and
continuous body movements. Fatigue is detined as failure of a material due to
repeated/cyclic loading or unloading (tensile or compressive stresses). In this eyelic
loading condition, microcracks/faws may be generated. These microscaled cracks
can initiate permanent plastic deformation which results in large erack propagation
of failure, During eyclic loading, several factors also contribute to mierocrack
generation such as frictional sliding of the mating surface, progressive wear, residual
stresses at grain boundaries, and stress due to shear. 9.2. Considerations of Material Characteristics 249
On the other hand, electrical properties of materials are Key factors. For example,
an artificial hand with a myoclectrical control isa new type of dynamic artificial hand
and a model “man-machine system” which is controlled by biological electricity
9.2.2 Material Degradation
The life span of biomedical products which are capable of offering required opera-
tional performance is extremely important. The degradation of materials has a
significant impact on the performance and reliability of an implanted device. There
are reasons that cause the degradation of materials. For metals and alloys, degrada-
tion is mainly caused by electrochemical reactions with bioliquids in a human body,
such as blood or gastric acid. Degradation of biopolymers may include (1) alteration
of the covalent interatomic bonds in polymer chains by chain scission or further
crosslinking, (2) the alteration of the intermolecular interactions between chains by
incorporation or loss of low-molecular-weight compounds, and (3) chemical reac.
tions in the aqueous environment such as oxidation and hydrolysis which can change
the properties of implanted polymers. Sometimes, methods of sterilizing biopol
mers (c.g., autoclaving and radiation) can significantly alter their properties,
resulting in an accelerated degradation rate after implantation. The degradation of
ceramics includes a preferential dissolution of impurities that results in crack prop-
gation, Bioactive ceramics and glasses degrade via their reactions with adjacent
tissues. For example, mineral components such as calcium phosphates can be
resorbed by osteoblasts.
9.2.3 Ton Release of Metals and Alloys
‘The surface biochemical properties of biomaterials are very important since the
surface interactions with surrounding tissues and fluids may affect that the biocom-
patibility of the materials and mechanical survival of the implanted device. When
metallic implants are placed in the electrolytic environment of the human body
(pH about 7.35 to 7.45, temperature about 38 °C, etc.) electrochemical reactions
‘may result in the release of metal ions coupled with corresponding reduction
reactions of constituents in the aqueous environment to maintain charge neutrality
This usually has a negative effect on mechanical factors such as pre-existing cracks,
surface abrasion, film adhesion, ete. The quantity of these metal ions released is a
function of the corrosion resistance of the metals. The compositions and ion release
rate of some metals and alloys widely used in biomedical devices are shown in
Table 9.2.
‘Metal ions generated by implants and their wear debris may remain in local
tissues, while some may bind to protein moieties that are then transported through
the blood stream and lymphatics to remote organs. Toxic effects of iron, titanium, 250 9 Biocompatible Material Selection
Table 92 The compositions and io release rate of metals and alloy
Ton release rate Guer/week)
Compositions (weight rao) (Ti [Ni__|Fe__(Cr__[Co
‘Siainless seed [Mainly Fe, 17% Cr, 1O%NI_[-_|1.15_|84 [oor [—
Cobaltchromium — | Mainly Co, 30% Cx, 08% Fe = [oe Joos or
“Tiana = ee
‘Titanium alloys | Mainly Tr
cobalt, chromium, and nickel in implant alloys and thei tolerance in human body
have been reported in the past decades of clinical research. Such tolerance is
quantitied as the maximum allowable daily intake of metal ions per liter of blood.
(On average, an adult human male who weighs 70 kg has a blood volume of about
5 liters.) The allowable daily intake of iron ions is 200 pay. Ion is essential for
the functioning of hemoglobin in red blood calls, helping to prevent anemia. A man
needs an average daily intake of 7 mg of iron and a woman 11 mg, which ean be
fultlled by a normal diet with an allowable daily intake of 35 yg/V/day. However,
excessive iron ions in a human body may cause conjunctivitis, choroidtis, and
retinitis. Cobalt is part of vitamin B12 which is essential for making red blood
cells and properly maintaining the nervous system. Yet, excessive exposure of cobalt
can cause an excessive level of red blood cells (polycythemia). Excessive cobalt is
toric tothe heart muscle and can cause heart muscle disease (toxic cardiomyopathy)
and even congestive heart flute, Itcan also cause enlargement and reduced activity
ofthe thyroid gland, The maximum allowable daly intake of chromium is 28 yg/!
day. The most common health problems of excessive chromium intake involve the
respiratory tract, and chromium compounds are carcinogenic. The daily intake of
nickel ions must not exceed 400 g/day. Nickel may lead to renal effects due to
carcinogenesis and hypersensitivity. Other serious harmful health effects from
exposure to nickel include chronic bronchitis and reduced lung function. On the
other hand, a person can tolerate titanium in relatively large doses. There is not yet
any biological role in human body known for titanium. AS much as 0.8 mg of
titanium can be in the human body without causing any known adverse health
reactions. In fact, most titanium passes through the body without being adsorbed.
However, titanium dioxide may induce a toxic effect on glial cells in the brain,
suggesting that exposure to ftanium dioxide may cause brain injury and pose a
health hazard. Regardless, titanium has relatively very good biocompatibility.
9.2.4 Wear of Materials
Material wear often occurs in artificial joints and at any moving parts with dircet
physical contacts in biomedical devices. Wear phenomena are intimately linked to
frictional processes. Roughly speaking, when the shearing stress is beyond the shear
strength of either material of the interface, the material bodies can slide on each 9.2. Considerations of Material Characteristics 2si
other. Such stress level is sufficiently high to cause the interfacial materials to
gradually become damaged as the shear stress is sufficiently high. Furthermore,
considering that most engineering surfaces are rough, the real contacting surfaces
between single asperities and the material particles come off from the damaged
asperities, The loss of material volume Vyy from one surface due to grinding between
‘wo material surfaces along a grinding distance Ly under a normal load F (Fig. 9.3)
hhas been characterized by the wear effect with the steady-state wear equation:
Flow
Vw Kaas
(on)
where Ky (which is a dimensionless quantity) is the standard wear coeflicient of the
surface with the volume loss Viy; and Fy is the Brinell hardness for the surface of the
sofler material surface. Notably, the volume loss can occur on both sides of the
grinding interface.
‘To a certain extent, the ratio F/Hy reflects the real contact area between the
materials as a softer material would deform further on the asperities of the hard
‘material surface with a larger contact area, Hence, the frictional force can be viewed
as the product of the shear strength and the real contact area of the softer material,
and therefore, the frictional force/stress is basically proportional to the normal
loading force/stress. In practice, while all asperity contacts contribute to friction,
ceven a very small fraction of the contacts can result in wear and the loss of volume.
‘The physical meaning of Kw isthe ratio of the volume removed Vw caused by wear
per unit sliding distance Lyy to the real interfacial area of contact, Ky can also be
interpreted as the proportion of the plastically deformed volume that is removed by
the wear process.
Fig. 9.3. Material wear and LOAD
volumetric loss
ASPIRITIES 22 9 Biocompatible Material Selection
Taking the artificial total knee joint (Fig, 9.4a) as an example, this device is
composed of a femoral prosthesis, a tibial prosthesis, and a patellar prosthesis, It is
made of two classes of materials: metal and plastic. The metal part includes the
‘femur, tibia, and patella joint of titanium alloy or cobalt-chromium alloy. The plastic
partis made of polyethylene. This ultrahigh-molecular-weight polyethylene can be
‘manufactured to attach to the metal part of the tibial and patellar joint in order to
reduce the friction with the femoral articular surface. After many years of wear due
to join movement, extensive wear, delamination, and cracks can be found on the
plastic spacer component of the total knee replacement device (Fig. 9.4b). In a very
bad case in which the bone dimensions and geometry change over years for some
patients, the lower limb force line changes, and the prosthesis wear will accelerate,
causing the product life to be shortened, More critically, the resulting pieces of
plastic from the wear could be released into the human body and may cause severe
health problems for the patients, such as osteolysis and other tissue necrosis.
9.2.5 Surface Roughness
Surface structure plays a key role in governing cell-material interactions. For
example, it has been reported that human mesenchymal stem cells (hMSCs) on
polycaprolactone with a surface roughness of ~2-3 im can facilitate osteogenic
(bone cell) differentiation. Similarly, osteogenic differentiation of hMSCs should
‘occur on tricaleium phosphate ceramics with a surface roughness of 2.78 ym. Over
® Thigh bone
(femur)
Metal replacement
of joint surface
plastic or metal
cement replacement of
bonding tibial surface
shin bone
ligament tea
Fig. 9.4 (a) A total knce replacement. (b) Two implanted plastic spacers afer years of wear
(Masib [5], American Joural of Biomedical Engineering) 9.2. Considerations of Material Characteristics 23
this range of surface roughness, the cells demonstrate higher survival rate (live cells-
to-dead cells ratio) and closer bone cell-related behaviors (c.g., osteocalcin produc-
tion). Higher contents of calcium, phosphate, and silicon ions can be released by
cells on such rough surfaces, facilitating the formation of osteoblastic
4ifferentiation-promoting adhesion components (¢.g., caleium-phosphate deposits).
(On the other hand, BMSCs growing on polished surfaces with a surface roughness of
~0.67 jm exhibit a significantly lower rate of osteogenic differentiation. Likewise, a
previous study on the effect of surface roughness for cells growing on a biodegrad-
able polycaprolactone indicates that an average PCL roughness of 0.93 jim alone can
serve as a compelling altemative to soluble osteogenic inducers for clinically
relevant orthopedic applications.
In addition to micrometer-scale surface structures, in vivo extracellular matrix
(ECM) enriched with specific nanotopographic features can affect different fates and
functions of cells. Nanoscale structured adhesive ligands, including silamentous
collagen, elastin, fibronectin, vitronectin, and laminin ranging in length from a few
to hundreds of nanometers, have been observed to be present in in vivo ECM,
Besides, nanotopographic structured adhesive molecules like integrin and the
nanopodia of cells have demonstrated through extracellular nanotopographic fea-
tures probing to have an effect on the enhancement of the cell membrane. Indeed,
biomaterials with nanoscale topography have been shown to regulate both self-
renewal and differentiation of pluripotent stem cells (PSCs) as well as mesenchymal,
neural, and hematopoietic adult stem cells. Therefore, cell-surface interactions can
bbe modulated by both the material type and surface roughness profiles.
9.2.6 Other Aspects Related to Biocompatibility
There are some other aspects related to biocompatibility, including the location of
device adhesion, the effect of cell separation, and mechanical behaviors. Material
gradation may cause the release of ions or molecules which can then trigger an
immune response and cause system inflammation. Hence, inflammatory response is
fone of the most important issues of biocompatibility that biomaterials need to
consider. Inflammation is @ host's immune response to foreign objects, and implants
are alien to the biological body. Improper implantation of a device can easily cause it
to be attacked by the biological host's immune system, leading to inflammation,
Inflammation is divided into acute inflammation and chronic inflammation. Severe
acute inflammation can lead to implantation failure, and improper treatment can lead
to widespread necrosis and life-threatening conditions. A mild inflammatory
response may turn into chronic inflammation, which could result in local tissue
fibrosis, further affecting the function of implants. Sometimes, biocompatibility
roquires long-term degradation, such as surgical sutures, whereas sometimes, bio-
compatibility requires long-term non-degradation, such as gold teeth. There are
many ways for a material to degrade, from basic water degradation and enzyme
degradation to advanced magnetic degradation, ultrasonic degradation, etc. By 24 9 Biocompatible Material Selection
means of spectic means, the degradation properties of biological materials can be
precisely controlled through several methods, including changing material geome-
tay, modifying the degree of crosslinking of polymers, and using hybrid material.
These are the areas in which biological material design needs to be considered.
‘As the body's main supplier of nutrients and oxygen, blood isa sensitive tissu.
In the case of blood contact (atiticial blood vessels, vascular stents, etc), using
inappropriate materials can lead to blood clots, and these clots are very serious and
very difficult to manage. For blood compatibility, in vitro testing ean be well
evaluated, and prior animal testing is a must. Improved blood compatibility often
involves improving the surface properties of the material. For incompatible mate
rials, this can mean increasing the structure ofa multilayer structure, simulating the
surface siucture ofa vessel, or improving the anticoagulabiity of the material using
a slow-release coating. Bone-related implants often provide mechanical structural
support, such as artificial joins, bone cement, and so on. Bone compatibility
involves promoting bone growth and connectivity to the bones, These properties
directly determine whether the implant can withstand the weight of the body and will
directly impact the time and degree of the patient's eventual recovery. Increased
bone compatibility of a material, in addition to using bone compatible materials
such as bio-slass, hydroxyapatite, and collagen as an extemal coating, can still be
done by changing the topology of the surface. In addition, the matching degree
between material and bone mechanical properties should also be considered. The
bone will gradually change depending on its environment, and the strength of the
boone to material connection will decrease the strength of the bone itself. In addition
to choosing suitable materials, the matching mechanical properties can be realized
by combining materials, increasing the gap inthe material, and reducing the relative
density of the material
9.3 Material Performance Index
9.3.1 Basic Concepts
The design of a mechanical component is specified by three factors: the functional
requirements (the need to carry loads, transmit heat, store elastic or thermal energy,
etc.) the geometry, and the properties of the material of which a component is made
(including its cost). The performance of the component can be defined by aspects
that are to be optimized, c.g., mass, volume, or cost. Optimum design can be
considered to be selection of the material and geometry which maximize material
performance in the final product. The optimization is subject to constrains, some of
‘Which are imposed by the material’s properties. There are three groups of paramet
which are said to be “separable”: (1) functional requirements, (2) geometry, and
(3) material properties. When these parameter groups are separable, the optimum
choice of material becomes independent of the design details. The optimum material
is the same forall geometries and all values of the functional requirements, Then, the 9.3. Material Performance Index 255
‘optimum material can be identified without solving the complete design problem or
ceven knowing all the details of the other separable parameters.
‘While we consider the mechanical properties of a biomedical device, we need to
know the basic design relationships for strength, stiffness, and different types of
Jeading and cross-sectional shapes. For example, for a solid bar/rod/cylinder with @
length L in tension or compression along its length direction without any permanent
deformation, the material yield strength 2yjey should be above the external tension/
compression load F divided by the cross-sectional area A, and the material elasticity
‘modulus £ relates to the structural length variation x as described by x = FLI(AE) as
Eq. 2.3. Fora bar/rodi/cylinder bending under a load F exerted at the center along its
length without permanent deformation, the material yield strength ays must be
sufliciently large:
sie = led Me (9.2)
where J isthe moment of inertia of the cross section, di the centroid to surface
distance, and Mis the bending moment. Foraplate strutire with engthZ, width W,
and thickness 7 (T'< W) as an example, the load is shared by both halves of the plate
each with a length 1/2, and thus, the bending moment M. = (F/2)(L2). Clea,
d= 772 and itean be checked thatthe moment of inertia, = WTPTI2. Therefore,
for the plate structure, ¢yiqy = JFLQWT), Furthermore, the material elastic
modulus £ ofthe bending structure can relate tothe distance atthe central position
along its length 3, as
FL
* = agar
(a)
In onder to further illustrate how to separate the functional requirements, geom-
ctzy, and material properties in our design considerations, we may first look into two
simple examples. Imagining that we are looking to select the optimum material for a
light and stiff beam (Fig. 9.5) as a component in an implanted device, i is required
that the beam has a fixed length of L where its width on the side 6 is adjustable to fit
the design requirement. This beam is fixed with both ends after implantation. The
mass of the beam is m = pbZ. where p is the density of the matetial. For a load
F acting at the mid-length position, the central deflection 8, is described as Eq. 9.3,
As a stiffer beam would have a smaller 6, upon the load P, we may consider the
‘structural stiffness” as PIS..
‘Our job here isto choose the “best” material fora larger structural stiffness and a
smaller mass. We may consider the following relation:
x FE. and thus 9.8) 256 9 Biocompatible Material Selection
Fig. 9.8. Key parameters e
for a simple supported beam
with a square crose-section :
bo
+
Gm) -@)G) °)
In the above equation, we can observe that the left term is related tothe functional
requirements ofthe design task, i. larger value ofthis term implies a smaller mass
oralarger structural stiffness. The irs term onthe right-hand side is aterm related to
the geometry requirement of Land the last term E/p” which only consists of material
properties For the required L, we should choose a material with a bigger value of Ef
p? for the better “performance,” ie., a larger value of the left term in the above
‘equation, Therefore, we may define a material performance index as E'"/p,
Let’s look atthe other example, Imagine that we need to design a light and
strong tubular beam with a fixed outer radius ras an intramedullary bone fxation
nail, It is mounted by screws on its ends with a fixed separating distance L. Its
function isto resist bending moments. The wall thickness ris fixed, whereas ris
adjustable to fit the design requirement. Consider thatthe moment of inertia of a
ring eros seetion with an outer radius of rand ring thickness 1 (1&7) [.= wr. The
intramedullary nail that ean withstand with an infinite life cyele under a limit of
bending moment Me is
(06)
where is elasticity modulus of the material. The objective is to minimize the mass
im. Now, we may express m by substituting Eg. 9.6:
07)
(8)
The better product performance should induce a smaller m and hence a larger value
of the left term in the above equation. The first term on the right-hand side only
depends on rand L which are the geometric requirements. The last term is related to
the material properties. Thus, we may detine a material performance index as E"/p. 9.3. Material Performance Index 2st
The above two examples demonstrate an enormous simplification: the overall
performance for the product is achieved by maximizing the material propertics,
which is called the “performance index.” Often, it is preferable to have lighter
implant devices because they would become additional weight at a local site in the
body, which may alter the body's balance and potentially cause risks during move-
‘ments of the patient. Furthermore, often used material performance indices arc listed
in Table 9.3 based on different object shapes and exerted loadings.
9.3.2 Ashby Charts of Biomaterials
In the previous section, we attempted to specify some product device problems in
three groups of quantities, ic. functional requirements, geometry constraints, and
‘material properties. Such quantities related to material properties induce the concept
cof “material performance index” and act as a guideline for us in choosing the
material for “best” product performance. A straightforward approach for picking
the “best” materials should be the computation ofthe material performance index for
all material candidates and the selection of the materials with the maximum perfor-
‘mance indices. For instance, the database of material properties can be found from
the Internet or computer software, such as a widely used computer program called
(Cambridge Materials Selector (CMS) which summarizes a broad range of material
properties and permits extensive evaluation of different materials. Also, a list of the
‘material properties for commonly used biomaterials is also available in Table 9.4
If we take a socond look at the common material performance indices as listed in
“Table 9.3, we may realize that in many typical cases, these indices can be expressed.
as the ratios of different intrinsic material properties. Considering that a material has
a material performance index relating to only two material properties, a value
‘Table 9.3. Some material performance indices and their coresponding cases for minimizing the
produet mass
To maximize [To maximum
strength | ttiness
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vanible
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slilinss length ned: section area free
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stifiness, length, width fixed, thickness fee
‘Cylindrical vessel wit intemal pressure: laste distortion, aa Bp
pressure, and radius fixed; wal thickness fee
4 yield stess or strength, E module of elasticity, G shear modulus, p density 9 Biocompatible Material Selection
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Poy = Xoo Xan Where Xipt and Xing based on two intrinsic material properties, and
a constant then we may convert the relation as
In (Pm) = Kp = In (Xi) /A — In (Xno), and thus (9.9)
where Ky is another constant, Then,
In (pt) = ln (Nya) + Kir (0.10)
In this cas, if we present the material properties Xj and Xqa a8 a log-log scale
plot, ie, In(Xq) against In(Xy2), materials having the value of Py, would lie along a
straight line in such plot. The slope of such line Ais determined by how Py is related
toXq and Xa The y-intercept ofthis plot Ky increases with P,. Therefore, we can
convert the material selection case listed in Table 9.4 to two key log-log scale plots
of different materials: strength against density (Fig. 9.6) and elasticity modulus
against density (Fig. 9.7), which are called the Ashby charts as such representation
has been proposed by Prof. Michacl Ashby at the University of Cambridge. In
particular, forthe ease of maximizing the structural stiffness of a bar in torsion,
the corresponding material performance index (=G'/p) should be applied with
another plot of In(G) against In(p), and G is the modulus of rigidity which can be
estimated by Eq, 2.15 using Poisson's ratios and elastic moduli listed in Table 9.4
‘To compare material performance indices, we may draw the lines with the
corresponding slopes of each index across each of the matcral points in the Ashby
é
Em
q i
v ae
70
7
Density, p (g/em’)
Fig. 9.6 Ashby char of strength against density 260 9 Biocompatible Material Selection
3
Re a
1
‘Modulus of Elasticity, E (GPa)
Density, p (@/em")
Fig. 9.7. Ashby char of elastic modulus against density
chart and then compare their y-intercepts. The material with the largest y-intercept
can be considered the “best” material, An easier way to search for the “best” material
graphically is to move the line up and down on the Ashby chart, while the slope is
‘maintained; the “best” material would be at the location intercepting with the moving
line with a highest level. This graphical technique is particularly useful as we can
search for the “best” materials for a product quickly and without any tedious
computations,
Problems
Problem 9.1
An intramedullary nail with a circular cross section is designed to be loaded with
force P at its free end to produce an allowable deflection of 8 = 4PL'/3Em*).
Explain why the material performance index based on the beam stiffness (P/6) can be
detined as Bip,
Problem 9.2
Are athletes likely to retum to sports after tibial fractures? Sports fans have
‘wimessed several horrific tibial fractures of athletes in games. In fact, 91.5% of Problems 261
patients with tibial shaft fractures treated surgically returned to sports. Typically,
tibial shaft fractures require surgery, usually in the form of an intramedullary nail
(a rod placed down the center of the bone with locking screws at the top and bottom
of the rod). Retuming to play requires the fracture to heal completely and in the
proper position and alignment of the bone pieces. The athlete must regain full
‘motion, strength, and function eventually.
In this question, we would like to think about issues on material selection and
dimension configuration of an intramedullary nail used for the surgery of Luciano
Almeida. The Brazilian soccer player suffered a severe injury during a match
between Botafogo and Flamengo in 2007. He was out for 5 months to make a full
recovery after surgery.
(@) Let's assume Luciano bas a body mass of 72 kg. Throughout a soccer game, the
legs of Luciano can be momentarily subjected toa force which is up to 20 times
his own weight. Determine the maximum () normal and Gi) shear stresses
developed in the tibia T of his leg atthe midsection a-a as shown in Fig. 9-P1
The cross section can be assumed to be circular having an outer diameter of 4 em
and an inner diameter of 2 em, Please note that a bone structure should be a
hollow shape. Assume the fibula F does not support a load.
(©) Here, we have the responsibility of designing a light and strong tubular
intaamedullary nal for the required surgery of Luciano, The intramedullary nail
should have a fixed outer radius R. The wall thickness T is adjustable, yet it
should be suficient to resist bending moment against permanent deformations.
The eyclic bending moment can be considered as the product of the shearing
force on the foot Fand the distance between the fixing screws at both ends ofthe
intramedullary nail (L), The bending moment (M,)is given as My = I6,LI(R x 8),
Where the moment of inertia J = 227, a, is the yield strength and 6 the nail
deflection. Our goal is to choose a metaV/alloy inducing a minimal mass m such
that Luciano will ary a minimal extra load (.e, the weight ofthe intramedullary
nail) on his leg. What isthe appropriate material performance index?
Fig. 2PL Momentary force
sting on a leg 262 9 Biocompatible Material Selection
(©) Can you draw the Ashby chart as the yield strength against density using the
‘material properties listed in Lecture 4 (page 12)? Which material would you
prefer to be used for the intramedullary nail?
(@) Suppose 1. is 35 em and R is 0.75 cm, What should the minimum mass of the
intramedullary nail be?
Problem 9.3
Extemal bone fixation plates are being considered for the upcoming surgery of a
patient, Currently, you are asked by the doctor for advice on which type of materials
are ideal as the structural materials. You are told that the bending of a fixed-fixed
supported rectangular plate under a line force P exerted at the beam center has the
‘maximum deflection 5= PL'/(192EN where Bis Young’s modulus and I= bd'/12is
the moment of inertia. The length L and width 6 of the plate are fixed, but the
thickness d may vary
(a) Please use thelist of material properties provided in the course webpage to draw
the (i) Young's modulus-density and (ii) stength-density Ashby's charts.
(b) Please suggest a material performance index for the minimized mass. Explain
your answer,
(©) Based on you own Ashby’s charts, identify a short list of candidate materials and
other possible selection considerations, Select the most appropriate material
(6) with explanations,
(@) Please suggest and elaborate on another material performance index for the
minimized material cost.
Problem 9.4
A rectangular bone fixation plate is planned to be implanted in a patient’s body as
shown in Fig. 9.P2. It is required to be able to have a displacement at its central
length position of smaller than & under a load P at the same position. Please consider
that the plate cross section has width W and thickness d, where the W is fixed but
dd can be changed by choosing a different plate model provided by the manufacturer.
The plate is fixed on the patient's bone by screws at its two ends with a separating
distance of the serews of L. Determine the following using Table 9.2
(a) The material that meets the design load and deflection limit atthe lowest weight,
Show all calculations
(b) The matcrial that meets the design load and deflection limit atthe lowest volume,
Show all calculations.
(c) Ifthe design load is double, what is the effect on your calculations?
(@) Ifthe deflection limit is halved, what is the effect on your calculations? Problems 263
Fig. 92. Coniiguration
and key parameters of
external bone fixation
Problem 9.5
‘A-70 kg patient has been arranged for an implantation surgery of an artificial knee
joint aftera severe car accident. The expected outcome after the surgery is described
as Fig. 9.P3a, The lower tibial plate is confirmed to be covered by a polyethylene
sheet, whereas the material for the upper femoral replacement component is yet
undetermined, There are currently two material candidates under consideration for
such femoral component: (1) stainless stcel and (2) cobalt-chromium alloy.
Now, we may consider the femoral geometry simplitied as shown in Fig. 9.P3b.
Assume that the femoral plate is a semicylindrical plate with outer radius (Ro)
30 mm, inner radius (R,) 25 mm, and width (Wena) 50 mm and that the both ends
are extended with a length (Lex) 10 mm. Furthermore, cach of the two extension
plates contains two cylindrical hinge rods (tilled with dark gray in the above figure;
diameter, Digg: Ieneth, Lyygc) Supporting the load during walking.
(2) Please suggest a material performance index for maximal strength upon bending,
of the hinge rods/beams with an explanation, and suggest the “better” material
candidate (ie., stainless steel or cobalt-chromium alloy).
Now, please consider that stainless steel has been chosen as the material for
the femoral component. Please further assume Linge = 10 mm and
Dainge = Sram.
(©) While walking, the foot of a 70 kg man is momentarily subjected to a force
(normal load on tibia) which is ~2 times of his weight. Please estimate the
‘maximum daily weight loss (unit: wp/day) of polyethylene from the artificial
joint caused by wear by considering that an individual should have <10,000
steps per day and that the “sliding distance” of the artificial joint is ~2R, for
every two steps (as one step for the let leg and the other for the right leg). Then,
what is the thickness of the wor polyethylene after 10 years? Please use the
‘material properties provided in Lecture notes.
(©) Please estimate the iton ion release rte (nit: g/day) due to biochemical effects,
(eg. interaction with blood) in the human body, based on info from Lecture
notes. Does it exceed the patient’s maximum allowable daily intake? 264 9 Biocompatible Material Selection
2 Femoralcomponent Bb
Fr been tn
Lng |
=)
replacement
‘spon
OY Sia poe sive view FRONT VIEW
Polyethylene Hi
Fig. 9.P3 (a) Aniticial knee joint, and (b) the key dimensional parameters forthe femoral
component
Ae
Problem 9.6
(a) Anartery is grafted with a synthetic material for a length of 5 mm and a radius of
| mm as shown in the Fig, 9.P4. Ifthe synthetic material is not compliant, sketch
how the vessel-graft combination will appear when pressure peaks in the blood.
circulatory system,
(b) Assume the radius of the artery is I mm, viscosity of blood is 3 x 10-* Pa x s,
and blood density is | x 10"* kg/m. Can you estimate the gradients of pressure
drop (G) for an overall blood velocity of SO mm s~" along the artery?
(6) Is the blood flow laminar or turbulent? Please explain
(@) Consider the grafting material has been wrongly chosen so that blood cells will
accumulate and form a layer over inner surfaces of the graft. Please sketch the
plot as the blood pressure gradient along the graft against the thickness of the
layer formed.
Problem 9.7
A cylindrical intramedullary nail is planned to be implanted inside the bone marrow
of a patient’s body as shown in Fig. 9.P5. It is required to be able to have a
displacement at its central length position of smaller than & under a load P at the
same position. Please consider that the plate cross section has a diameter D, where
D can be changed by choosing a different rod model provided by the manufacturer. Problems 265
Fig. 9.PS A rod xed by
screws on is both ends on a
patient's bone
The rod is fixed on the patient's bone by screws at its two ends with a separating
distance between the screws of L. Determine the following using Table 9.2 and given
that the moment of inertia fora circular cross section is «D'V64.
(a) The material that meets the design load and deflection limit atthe lowest weight,
Show all calculations.
(b) The material that meets the design load and deflection limit atthe lowest volume.
Show all calculations,
(6) I the design load is doubled, what is the effect on your calculations?
(@) Ifthe deflection limit is halved, what is the effect on your calculations?
Problem 9.8
A hollow cylindrical intramedullary nail is planned to be implanted inside the bone
marrow of a patient's body. It is required to be able to have a displacement at its
central length position of smaller than 6 under a load P at the same position. Please
consider thatthe plate cross section has an outer diameter D and a shell thickness 7
where D is fixed and T can be changed by choosing a different rod model provided
by the manufacturer. The rod is fixed on the patient's bone by screws at its two ends
with a separating distance between the screws of L. Determine the following using
Table 9.2 and given that the moment of inertia for a ring cross section is xD°7I8.
(a) The material that meets the design load and deflection limit atthe lowest weight.
Show all calculations,
(b) The material that meets the design load and deflection limit atthe lowest volume.
Show all calculations.
(©) Ifthe design load is doubled, what is the effect on your calculations?
(@) Ifthe deflection limit is halved, what is the effect on your calculations?
Problem 9.9
‘We wish to select the optimum material fora light, stiff beam. The beam with square
cross section is b em on a side and L long. A is the area of the beam across section,
and p and E are the density and Young's modulus of the material, respectively. For
the beam being stretched with a force F, the beam extension 3 is 8 = FLIAE. 266 9 Biocompatible Material Selection
(a) Explain why the material performance index can be defined as E/p. Please
clearly describe the reasons and arguments in your explanation. (Minor marks
will be deduced for unclear descriptions.)
(b) Consider now that we have three classes of materials: engineering metal alloys,
engineering polymers, and engineering ceramics. With the help of the Ashby
chart given above, can you select the “best” material class for the application
described in this question? Please explain clearly for your answer with the Ashby
char.
Problem 9.10
Imagine that you need to design a light and strong tubular beam with a fixed outer
radius r as an intramedullary bone fixation nail. It is mounted by screws on its ends
with a fixed separating distance L. Its function isto resist bending moment. The wall
thickness 1 is adjustable to fit the design requirement, whereas ris fixed. Consider
that the moment of inertia of a ring cross section with an outer radius of r and ring
thickness ¢(¢
