Applications
Content
SECTION
II.5
Applications of Biomaterials
CHAPTER II.5.1 INTRODUCTION:
APPLICATIONS OF BIOMATERIALS
Frederick J. Schoen1 and Jack E. Lemons2
1Professor
of Pathology and Health Sciences and Technology (HST),
Harvard Medical School, Executive Vice Chairman, Department of
Pathology, Brigham and Women’s Hospital, Boston, MA, USA
2University Professor, Schools of Dentistry, Medicine and
Engineering, University of Alabama at Birmingham,
Birmingham, AL, USA
Most students of biomaterials have a strong interest in
medical or dental applications. Biomaterials are used for
the construction of components in an extensive array of
devices across a wide range of medical disciplines. When
considering the applications of biomaterials as a section
focus, a primary consideration is on outcomes of treatments. Outcomes are evaluated in terms of the discipline
and the specific biomaterial properties needed for a highly
specific application to improve outcomes of patients with
specific clinical problems. For example, a total joint
replacement has very different considerations than a
tooth root replacement, although both anchor in bone
for function. Similarly, requirements for a heart valve
are very different compared to a vessel replacement or
an endovascular stent, although all have extensive blood
contact and some biomaterial properties are in common.
The following chapters in Part II present a broad spectrum of biomaterials applications and the key properties
needed for specific physiological environments. The Cardiovascular section starts with Nonthrombogenic Biomaterials (II.5.2) by Sefton and Cardiovascular Medical Devices
(II.5.3). Subsections A–D describe Valves (II.5.3A), Endovascular Stents, Vascular grafts, and Stent Grafts (II.5.3B),
Other Cardiovascular Devices (II.5.3C), all by Schoen and
Padera, and Implantable Cardiac Assist Devices and IABPs
(II.5.3D) by Simon, Borovetz and Wagner. The emphasis
shifts to artificial cells (II.5.4) by Chang, and Extracorporeal
Artificial Organs (II.5.5) by Ritchie. Two chapters with musculoskeletal emphasis are Orthopedic and Dental Applications (II.5.6 and II.5.7) by Hallab and Jacobs, and Lemons
and Misch, respectively. Adhesives and Sealants (II.5.8) are
presented by Watts. Ophthalmologic Applications (II.5.9)
and subdivisions on contact lenses (II.5.9A), IOLs (II.5.9B),
Corneal Inlays (II.5.9C), Glaucoma Drains (II.5.9D), and
Retinal Prostheses (II.5.9E) are presented by Steinert and
Jain; Jacob; Patel; Cunanan; Cunanan; and Humayun et
al. respectively. Chapters follow on Bioelectrodes (II.5.10),
Cochlear Prostheses (II.5.11) and Stimulating Electrodes
(II.5.12) implants, Biosensors (II.5.13), Burn Dressings and
Skin Substitutes (II.5.14), and Sutures (II.5.15) by Venugopalan and Ideker; Spelman; Peckhan, Ackermann, and Moss;
LaFleur and Yager; Helm, Orgill B., Ogawa and Orgill D.;
and Taylor and Shalaby, respectively. Chapters on applications are extended in the next series on Drug Delivery
Systems (II.5.16), with subsections on Injected Nanocarriers PEGylation, Targeting, Polymer–Drug Conjugates,
Liposomes, Polymeric Micelles, Dendrimers, Nucleic Acid
Delivery, and Polymeric and Albuminated Drug Nanoparticles, collectively by Hoffman, and Gombotz; Pun; Stayton, Ghosn, and Wilson J. The drug delivery systems
(DDS) chapters continue with Injected Degradable Depot
DDS (II.5.16C), Implants and Inserts (II.5.16D), Smart DDS
(II.5.16E), Transdermal DDS (II.5.16F), and Oral DDS
(II.5.16G) by Gombotz; Wright and Kleiner; Hoffman;
Cleary; and Wilson C., respectively. This section closes with
chapters on Diagnostic Applications (II.5.17) by Domingo,
Hawkins, Peck, and Weigl, and Silicones (II.5.18) by Curtis
and Colas.
A central theme is the generation and use of design
criteria based on desired functionality, potentially deleterious biomaterials–tissue interaction mechanisms, pathologies of the underlying conditions for which the implant
is needed, and the basic properties of the various biomaterials available or needing to be developed. It should not
be surprising that considerable research and development
has led to clinically used devices with active mechanical,
electrical, biologic or mass exchange functions.
Biomaterials applications and surgical implant technology assume a key role in current clinical practice. In
2000, it was estimated that approximately 20 million individuals had an implanted medical device. The number is
growing, but is difficult to assess precisely. A recent article
in The Wall Street Journal (July 18, 2011) summarized
the five most frequently implanted medical devices in the
US: artificial eye lenses (>2.5 million per year); tympanostomy ear tubes (>0.75 million per year); coronary arterial stents (>0.5 million per year); prosthetic knee joints
(>0.5 million per year); and metal screws, pins, plates,
757
758
SECTION II.5 Applications of Biomaterials
and rods (>450,000 per year). The economic impact is
massive; in 2000 costs associated with prostheses and
organ replacement therapies exceeded $300 billion US
per year, and comprised >1% of the US gross domestic
product (GDP) and nearly 8% of total healthcare spending worldwide (Lysaght and O’Loughlin, 2000). Thus,
medical devices contribute to the expense associated
with modern healthcare in the United States, which is
presently in excess of 17% of GDP, continues to grow,
and has become a significant public policy issue. For the
widely used artificial eye lenses, at 2.5 million surgeries
performed annually at a rate of about $3200 to $4500
per eye, the total expenditure is estimated at between
$8 billion and $10 billion per year. The use of health
technology assessment tools can assist those in leadership positions in making rational decisions as to which
new technologies to adopt, based on evaluation of clinical effectiveness, cost-effectiveness, and risk to patients.
Most implants serve their recipients well for extended
periods by alleviating the conditions for which they were
implanted. Considerable effort is expended in understanding biomaterials–tissue interactions and eliminating
patient–device complications (the clinically important
manifestations of biomaterials–tissue interactions). Moreover, many patients receive substantial and extended
benefit, despite complications. For example, heart valve
disease is a serious medical problem affecting over 30,000
people per year in the United States. Patients with aortic
stenosis (the most common form of heart valve disease)
have a 50% chance of dying within approximately three
years without surgery. Surgical replacement of a diseased
valve leads to an expected survival of 70% at 10 years, a
substantial improvement over the natural course. However, of these patients whose longevity and quality of life
have clearly been enhanced, approximately 60% will suffer a serious valve-related complication within 10 years
after the operation. Thus, long-term failure of biomaterials
leading to a clinically significant event does not preclude
clinical success, for a significant duration and overall.
The range of tolerable risk of adverse effects varies
directly with the medical benefit obtained by the therapy.
Benefit and risk go hand-in-hand, and clinical decisions are
CHAPTER II.5.2 NONTHROMBOGENIC
MATERIALS AND STRATEGIES: CASE
STUDY
Michael V. Sefton1, Cynthia H. Gemmell1,
and Maud B. Gorbet2
1Department
of Chemical Engineering and Applied Chemistry,
Institute of Biomaterials and Biomedical Engineering, University of
Toronto, Canada
2Department of Systems Design Engineering, University of Waterloo,
Canada
ISO Standard 10993-4, Biological Evaluation of
Medical Devices Part 4: The Effects on Blood (ISO/
made to maximize the ratio of benefit to risk. The tolerable
benefit–risk ratio may depend on the type of implant and
the medical problem it is used to correct. Thus, more risk
can be tolerated with a heart assist device (a life-sustaining
implant) than with a prosthetic hip joint (an implant that
relieves pain and disability and enhances function), and
much more risk than with a breast implant (an implant with
predominantly cosmetic benefit). As an example, total hip
arthroplasties (THAs) with metal-on-metal (MoM) or more
correctly cobalt alloy-on-cobalt alloy articulating surfaces,
have been used clinically since the 1950s. Applications of
recent generation THAs exceed hundreds of thousands.
Very recently, metallic debris products in larger quantities
have been associated with adverse foreign-body reactions,
need for revisions, and a recall action of one design/product;
for updated information on this topic, students are referred
to the US Food and Drug Administration (FDA) web site
(http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/ImplantsandProsthetics/MetalonMetalHipImplants/default.htm), the American Academy of Orthopaedic
Surgeons website (AAOS.org) and/or the American Society
for Testing and Materials website (ASTM.org). An ASTM
symposium Standard Technical Publication (STP) on this
topic should be available in late 2012.
In summary, this section explores the most widely
used applications of materials in medicine, biology, and
artificial organs. The progress made in many of these
areas has been substantial. In most cases, the individual
chapters describe a device category from the perspective
of the clinical need, the armamentarium of devices available to the practitioner, the results and complications,
and the challenges to the field that limit success.
BIBLIOGRAPHY
US Food and Drug Administration (FDA). (2012). http://www.fda.
gov/MedicalDevices/ProductsandMedicalProcedures/ImplantsandProsthetics/MetalonMetalHipImplants/default.htm.
Lysaght, M. J., & O’Loughlin, J. A. (2000). Demographic scope
and economic magnitude of contemporary organ replacement
therapies. ASAIO J., 46, 515–521.
The Wall Street Journal. (2011). http://247wallst.com/2011/07/18/
the-eleven-most-implanted-medical-devices-in-america/. July 18.
AAMI 1995), which manufacturers of medical devices
need to use as guidance to register their products,
includes thrombosis and coagulation among the tests
that need to be done. However, specific test methods are not detailed. With a view to clarifying this
question, a series of plasma-modified tubes (along
with an unmodified control and other commercially
available tubing) were prepared, surface characterized, and exposed to heparinized whole blood
(1 U/mL heparin) for one hour at 37°C (Sefton et al., 2001).
The surface modifications included several different
plasma vapors (H2O, CF4, and fluorine). The 1.5 mm
Due to an error in production the full version of this chapter is available in Appendix E.
II.5
Applications of Biomaterials
CHAPTER II.5.1 INTRODUCTION:
APPLICATIONS OF BIOMATERIALS
Frederick J. Schoen1 and Jack E. Lemons2
1Professor
of Pathology and Health Sciences and Technology (HST),
Harvard Medical School, Executive Vice Chairman, Department of
Pathology, Brigham and Women’s Hospital, Boston, MA, USA
2University Professor, Schools of Dentistry, Medicine and
Engineering, University of Alabama at Birmingham,
Birmingham, AL, USA
Most students of biomaterials have a strong interest in
medical or dental applications. Biomaterials are used for
the construction of components in an extensive array of
devices across a wide range of medical disciplines. When
considering the applications of biomaterials as a section
focus, a primary consideration is on outcomes of treatments. Outcomes are evaluated in terms of the discipline
and the specific biomaterial properties needed for a highly
specific application to improve outcomes of patients with
specific clinical problems. For example, a total joint
replacement has very different considerations than a
tooth root replacement, although both anchor in bone
for function. Similarly, requirements for a heart valve
are very different compared to a vessel replacement or
an endovascular stent, although all have extensive blood
contact and some biomaterial properties are in common.
The following chapters in Part II present a broad spectrum of biomaterials applications and the key properties
needed for specific physiological environments. The Cardiovascular section starts with Nonthrombogenic Biomaterials (II.5.2) by Sefton and Cardiovascular Medical Devices
(II.5.3). Subsections A–D describe Valves (II.5.3A), Endovascular Stents, Vascular grafts, and Stent Grafts (II.5.3B),
Other Cardiovascular Devices (II.5.3C), all by Schoen and
Padera, and Implantable Cardiac Assist Devices and IABPs
(II.5.3D) by Simon, Borovetz and Wagner. The emphasis
shifts to artificial cells (II.5.4) by Chang, and Extracorporeal
Artificial Organs (II.5.5) by Ritchie. Two chapters with musculoskeletal emphasis are Orthopedic and Dental Applications (II.5.6 and II.5.7) by Hallab and Jacobs, and Lemons
and Misch, respectively. Adhesives and Sealants (II.5.8) are
presented by Watts. Ophthalmologic Applications (II.5.9)
and subdivisions on contact lenses (II.5.9A), IOLs (II.5.9B),
Corneal Inlays (II.5.9C), Glaucoma Drains (II.5.9D), and
Retinal Prostheses (II.5.9E) are presented by Steinert and
Jain; Jacob; Patel; Cunanan; Cunanan; and Humayun et
al. respectively. Chapters follow on Bioelectrodes (II.5.10),
Cochlear Prostheses (II.5.11) and Stimulating Electrodes
(II.5.12) implants, Biosensors (II.5.13), Burn Dressings and
Skin Substitutes (II.5.14), and Sutures (II.5.15) by Venugopalan and Ideker; Spelman; Peckhan, Ackermann, and Moss;
LaFleur and Yager; Helm, Orgill B., Ogawa and Orgill D.;
and Taylor and Shalaby, respectively. Chapters on applications are extended in the next series on Drug Delivery
Systems (II.5.16), with subsections on Injected Nanocarriers PEGylation, Targeting, Polymer–Drug Conjugates,
Liposomes, Polymeric Micelles, Dendrimers, Nucleic Acid
Delivery, and Polymeric and Albuminated Drug Nanoparticles, collectively by Hoffman, and Gombotz; Pun; Stayton, Ghosn, and Wilson J. The drug delivery systems
(DDS) chapters continue with Injected Degradable Depot
DDS (II.5.16C), Implants and Inserts (II.5.16D), Smart DDS
(II.5.16E), Transdermal DDS (II.5.16F), and Oral DDS
(II.5.16G) by Gombotz; Wright and Kleiner; Hoffman;
Cleary; and Wilson C., respectively. This section closes with
chapters on Diagnostic Applications (II.5.17) by Domingo,
Hawkins, Peck, and Weigl, and Silicones (II.5.18) by Curtis
and Colas.
A central theme is the generation and use of design
criteria based on desired functionality, potentially deleterious biomaterials–tissue interaction mechanisms, pathologies of the underlying conditions for which the implant
is needed, and the basic properties of the various biomaterials available or needing to be developed. It should not
be surprising that considerable research and development
has led to clinically used devices with active mechanical,
electrical, biologic or mass exchange functions.
Biomaterials applications and surgical implant technology assume a key role in current clinical practice. In
2000, it was estimated that approximately 20 million individuals had an implanted medical device. The number is
growing, but is difficult to assess precisely. A recent article
in The Wall Street Journal (July 18, 2011) summarized
the five most frequently implanted medical devices in the
US: artificial eye lenses (>2.5 million per year); tympanostomy ear tubes (>0.75 million per year); coronary arterial stents (>0.5 million per year); prosthetic knee joints
(>0.5 million per year); and metal screws, pins, plates,
757
758
SECTION II.5 Applications of Biomaterials
and rods (>450,000 per year). The economic impact is
massive; in 2000 costs associated with prostheses and
organ replacement therapies exceeded $300 billion US
per year, and comprised >1% of the US gross domestic
product (GDP) and nearly 8% of total healthcare spending worldwide (Lysaght and O’Loughlin, 2000). Thus,
medical devices contribute to the expense associated
with modern healthcare in the United States, which is
presently in excess of 17% of GDP, continues to grow,
and has become a significant public policy issue. For the
widely used artificial eye lenses, at 2.5 million surgeries
performed annually at a rate of about $3200 to $4500
per eye, the total expenditure is estimated at between
$8 billion and $10 billion per year. The use of health
technology assessment tools can assist those in leadership positions in making rational decisions as to which
new technologies to adopt, based on evaluation of clinical effectiveness, cost-effectiveness, and risk to patients.
Most implants serve their recipients well for extended
periods by alleviating the conditions for which they were
implanted. Considerable effort is expended in understanding biomaterials–tissue interactions and eliminating
patient–device complications (the clinically important
manifestations of biomaterials–tissue interactions). Moreover, many patients receive substantial and extended
benefit, despite complications. For example, heart valve
disease is a serious medical problem affecting over 30,000
people per year in the United States. Patients with aortic
stenosis (the most common form of heart valve disease)
have a 50% chance of dying within approximately three
years without surgery. Surgical replacement of a diseased
valve leads to an expected survival of 70% at 10 years, a
substantial improvement over the natural course. However, of these patients whose longevity and quality of life
have clearly been enhanced, approximately 60% will suffer a serious valve-related complication within 10 years
after the operation. Thus, long-term failure of biomaterials
leading to a clinically significant event does not preclude
clinical success, for a significant duration and overall.
The range of tolerable risk of adverse effects varies
directly with the medical benefit obtained by the therapy.
Benefit and risk go hand-in-hand, and clinical decisions are
CHAPTER II.5.2 NONTHROMBOGENIC
MATERIALS AND STRATEGIES: CASE
STUDY
Michael V. Sefton1, Cynthia H. Gemmell1,
and Maud B. Gorbet2
1Department
of Chemical Engineering and Applied Chemistry,
Institute of Biomaterials and Biomedical Engineering, University of
Toronto, Canada
2Department of Systems Design Engineering, University of Waterloo,
Canada
ISO Standard 10993-4, Biological Evaluation of
Medical Devices Part 4: The Effects on Blood (ISO/
made to maximize the ratio of benefit to risk. The tolerable
benefit–risk ratio may depend on the type of implant and
the medical problem it is used to correct. Thus, more risk
can be tolerated with a heart assist device (a life-sustaining
implant) than with a prosthetic hip joint (an implant that
relieves pain and disability and enhances function), and
much more risk than with a breast implant (an implant with
predominantly cosmetic benefit). As an example, total hip
arthroplasties (THAs) with metal-on-metal (MoM) or more
correctly cobalt alloy-on-cobalt alloy articulating surfaces,
have been used clinically since the 1950s. Applications of
recent generation THAs exceed hundreds of thousands.
Very recently, metallic debris products in larger quantities
have been associated with adverse foreign-body reactions,
need for revisions, and a recall action of one design/product;
for updated information on this topic, students are referred
to the US Food and Drug Administration (FDA) web site
(http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/ImplantsandProsthetics/MetalonMetalHipImplants/default.htm), the American Academy of Orthopaedic
Surgeons website (AAOS.org) and/or the American Society
for Testing and Materials website (ASTM.org). An ASTM
symposium Standard Technical Publication (STP) on this
topic should be available in late 2012.
In summary, this section explores the most widely
used applications of materials in medicine, biology, and
artificial organs. The progress made in many of these
areas has been substantial. In most cases, the individual
chapters describe a device category from the perspective
of the clinical need, the armamentarium of devices available to the practitioner, the results and complications,
and the challenges to the field that limit success.
BIBLIOGRAPHY
US Food and Drug Administration (FDA). (2012). http://www.fda.
gov/MedicalDevices/ProductsandMedicalProcedures/ImplantsandProsthetics/MetalonMetalHipImplants/default.htm.
Lysaght, M. J., & O’Loughlin, J. A. (2000). Demographic scope
and economic magnitude of contemporary organ replacement
therapies. ASAIO J., 46, 515–521.
The Wall Street Journal. (2011). http://247wallst.com/2011/07/18/
the-eleven-most-implanted-medical-devices-in-america/. July 18.
AAMI 1995), which manufacturers of medical devices
need to use as guidance to register their products,
includes thrombosis and coagulation among the tests
that need to be done. However, specific test methods are not detailed. With a view to clarifying this
question, a series of plasma-modified tubes (along
with an unmodified control and other commercially
available tubing) were prepared, surface characterized, and exposed to heparinized whole blood
(1 U/mL heparin) for one hour at 37°C (Sefton et al., 2001).
The surface modifications included several different
plasma vapors (H2O, CF4, and fluorine). The 1.5 mm
Due to an error in production the full version of this chapter is available in Appendix E.
