DOW-UAP-D119, AAWSAP DIRD, Biomaterials, January 2010

This document is a Defense Intelligence Reference Document (DIRD), a technical reference format used by the Defense Intelligence Agency (DIA) to capture baseline knowledge on a specific topic for later analytic use. DIRDs are best understood as reference and synthesis products rather than as original research. It is one of 38 DIRDs produced under the Advanced Aerospace Weapon System Applications Program (AAWSAP) between 2009 and 2011. Because AAWSAP’s scope permitted a broad range of supporting topics, not every DIRD in the series directly concerns aerospace systems or future threat assessment. The following summary reflects the DIRD’s scope and framing at the time of writing and should not be read as implying current validation of the concepts discussed. This DIRD is a broad survey of biomaterials, including metals, polymers, ceramics, glasses, and composites designed to interact with living tissue, and argues that their value depends mainly on biocompatibility, reliability, and careful matching of material properties to specific medical uses. The report reviews major application areas including biosensors, implants, cardiovascular devices, contact lenses, drug delivery systems, tissue constructs, titanium devices, and dialysis membranes, emphasizing that no single biomaterial works best in every setting. Its overall conclusion is that biomaterials are already foundational to a large medical-device industry and save or improve millions of lives, but that progress tends to be slow because safety testing is stringent; as a result, most advances come from improved ways of applying established materials such as silicone, Teflon, biodegradable polymers, ceramics, and titanium in new devices and clinical settings rather than from radically new substances.

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Defense
Intelligence
Reference
Document
Acquisition Threat Support
7 January 2010
!COD: 1 December 2009
DIA-08-0912-006
Biomaterials
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Biomaterials
Prepared by:
Acquisition Support Division (DW0-3)
Defense Warning Office
Directorate for Analysis
Defense Intelligence Agency
Author:
AAP Person 65
Administrative Note
COPYRIGHT WARNING: Further dissemination of the photographs in this publication is not authorized.
This product is one in a series of advanced technology reports produced in FY 2009
under the Defense Intelligence Agency, Defense Warning Office's Advanced Aerospace
Weapon System Applications (AAWSA Pro ram. Comments or uestions pertaining to
this document should be addressed t AAP Person 1 AAWSA Program
Manager, Defense Intelligence Agency, ATTN: CLAR/DWO-3, Bldg 6000, Washington,
DC 20340-5100.
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Contents
Introduction ...........................................................................................................vi
Importance of Biocompatibility .........................................................................vii
Science of Biomaterials .....................................................................................vii
Biomaterials for Biosensors ................................................................................... 1
Biomaterials for Biomedicine ................................................................................. 2
Biomedical Silicones - Polydimethylsiloxanes .................................................... 2
Silicone Chemistry.............................................................................................. 4
Silicone in Biomedical Products.......................................................................... 4
Teflon ................................................................................................................. 6
Biodegradable Polymers..................................................................................... 7
Biodegradation Advantages ............................................................................... 8
Degradable Biomaterials .................................................................................... 8
Polylactic Acid and Polyglycolic Acid .................................................................. 8
Polyethylene Glycol or Polyethylene Oxide....................................................... 10
Hydrogels......................................................................................................... 10
Titanium - Hip and Knee Joints ........................................................................ 11
BioCeramics ..................................................................................................... 11
Dental Ceramics ............................................................................................... 13
Tissue Constructs as Biomaterials ...................................................................... 13
Cardiovascular Biomaterials............................................................................. 15
Stent Biomaterials............................................................................................ 18
Nitinol as a Biomaterial .................................................................................... 19
Contact Lenses ................................................................................................. 19
Drug Delivery Polymers.................................................................................... 20
Medical Titanium as a Biomaterial.................................................................... 22
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Biomaterials in Dialysis .................................................................................... 24
Summary and Recommendations ......................................................................... 25
Figures
Figure 1. Biomaterial Applications in Medical Devices ............................................vi
Figure 2. Common Medical Devices That Use Biomaterials ...................................viii
Figure 3. Biomaterials Such as Polycarbonates, Cellulose, and Silicones Used in
Membranes for Sensors, Dialyzers, and Oxygenators .............................. 1
Figure 4. Photograph of Silicone (polydimethyllsiloxane) Biomedical Implants
Used in Breast Reconstructive Surgery ................................................... 3
Figure 5. Silicone Chemical Groups ........................................................................ 4
Figure 6. Silicone Tracheostomy Tube .................................................................... 5
Figure 7. Silicone Sheets Used Under the Skin as a Physical Supporting Layer for
Repair of Scar Tissue ............................................................................... 5
Figure 8. Teflon Structure ...................................................................................... 6
Figure 9. Expanded PTFE (Gore-Tex or ePTFE) Used in Lip Implants...................... 7
Figure 10. Biodegradable Polymers........................................................................ 7
Figure 11. Structure of Polylactic Acid (a Biodegradable Polymer) ........................ 9
Figure 12. Biodegradable PLA as an Antiadhesion Barrier after Open-Heart
Surgery ................................................................................................. 9
Figure 13. Biodegradable Polymers Based on Copolymers of Polylactic Acid and
Polyethylene Glycol (Polysciences Inc) ............................................... 10
Figure 14. Dots of Hydrogel.................................................................................. 10
Figure 15. Various Titanium Components Used in Hip Joint Replacement ............ 11
Figure 16. Hydroxyapatite Porous Bone-Like Structure After Commercial
Processing .......................................................................................... 12
Figure 17. Bioceramic Used in Artificial Hip Replacement Component.................. 12
Figure 18. Computer-Based Sculpted Ceramic Teeth ............................................ 13
Figure 19. Scaffold-Guided Tissue Regeneration .................................................. 14
Figure 20. Biodegradable Material CSLG Deposited in a Honeycomb Structure to
Allow Infiltration by Living Cells While in a Submerged Cell Culture ... 15
Figure 21. Some of the More Popular Biomedical Devices and Duration of Their
Blood Contact...................................................................................... 16
Figure 22. Gore Medical Teflon Foam Used in Vascular Grafts .............................. 16
Figure 23. Illustration of Treatment of an Atrial Septal Defect Using a
Teflon-Based Product Manufactured by Gore, Inc............................... 17
Figure 24. Stainless Steel and Teflon Bjork Shiley Heart Valve ............................ 18
Figure 25. Illustration of Stent Placement ........................................................... 18
Figure 26. Nitinol Stent ........................................................................................ 19
Figure 27. Contact Lens........................................................................................ 20
Figure 28. Schematic Representation of Biodegradable (Bioerodible) Drug
Delivery Device ................................................................................... 21
Figure 29. Photomicrograph of Titanium Metal (Appears Black in This Photo)
in an Intimate Integration With Living Bone ....................................... 23
Figure 30. Illustration (Left) and Photograph (Right) of a Blood Dialyzer as
Used in Medicine ................................................................................. 24
Figure 31. Cuprophane Membrane Passes Blood Waste Products (Violet and
Orange Dots) Through Pores and Blocks Passage of Red Blood Cells .. 25
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Biomaterials
Introduction
Biomaterials are metals, ceramics, polymers, glasses, carbons, and composite
materials intended to interface with biological systems. They are often used to
treat, augment, or replace bodily tissues, organs, or functions. Such materials
are used in various forms, including molded or machined parts, coatings,
fibers, films, foams, and fabrics. Biomaterials are usually nonliving, but recent
definitions also include living skin and tissues produced in culture.
A biocompatible material is different from a biological material produced by a
biological system, such as bone. Artificial hips, vascular stents, artificial
pacemakers, and catheters are all made of biocompatible materials that
typically have a synthetic origin. An extraordinarily wide range of medical
devices are made from biomaterials. Figure 1 shows some representative
examples of medical devices that use biomaterials.
Finger joint Breast implant Heart valve
.lloooe rubber
Hip j int tifi ial heart
poly\lr
Figure 1. Biomaterial Applications in Medical Devices
Encompassing elements of medicine, biology, chemistry, and materials science,
biomaterials science has experienced steady and strong growth over its
approximately half-century history.
Although biomaterials are used primarily for medical applications, they are
also used to grow cells in culture, to assay for blood proteins in the clinical
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laboratory, in processing biomolecules in biotechnology, for fertility regulation
implants in cattle, in diagnostic gene arrays, in the aquaculture of oysters, and
for investigational cell-silicon "biochips." The common thread in these
applications is the interaction between biological systems and synthetic or
modified natural materials.
Biomimetic materials, in contrast, are not made by living organisms but have
compositions and properties similar to materials made by living organisms.
For example, the calcium hydroxyapatite coating found on many artificial
hips-used as metal-bone interface cement to make it easier to attach
implants to bone-is similar to the coating found in mollusk shells.
IMPORTANCE OF BIOCOMPATIBILITY
Biocompatibility is an important issue in biomedical implants and sensors. A
material-tissue interaction that results from implanting a foreign object in the
body is a major obstacle to developing stable and long-term implantable
devices and sensors.
The processes that occur when sensors are placed in the complex living
environment of the human body are sometimes known as biofouling. In
biofouling, the physical or chemically sensitive portion of the sensor interface
becomes coated with proteins, blood-formed elements, adherent
immunological cells, and sometimes forms of scar tissue that tend to isolate
the sensor from the rest of the body environment. This response of tissue is a
foreign body reaction to any object introduced in tissue that does not express
surface characteristics that identify it as part of the host tissues.
Experiences of many investigators (more than 600 reported studies since 1996)
with the biocompatibility of biomaterials related to the function of implanted
biosensors have been poor such that many companies have abandoned
implantable sensor devices altogether. Rather, the recent trend in medical
biosensors is toward placing them outside the body. Newer sensors are often
based on optical principles in an effort to obviate the biocompatibility and
biomaterial issues of placing sensors inside the human body.
SCIENCE OF BIOMATERIALS
The study and use of biomaterials bring together researchers from diverse
academic backgrounds who must communicate clearly. Professions that
intersect in the development, study, and application of biomaterials include
bioengineer, chemist, chemical engineer, electrical engineer, mechanical
engineer, materials scientist, biologist, microbiologist, physician, veterinarian,
ethicist, nurse, lawyer, regulatory specialist, and venture capitalist.
The number of medical devices used each year in humans is very large. Figure
2 estimates usage for common devices, all of which employ biomaterials.
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Numbers of Medical Devices/yr. Worldwi,.,......--
intraocular lens 7,000,
contact lens 75,000,000
vascular graft 400,000
hip and knee prostheses 1,000,000
catheter 300,000,000
heart valve 200,000
stent (cardiovascular) >2,000,000
breast implant 300,000
dental implant 500,000
pacemaker 200,000
renal d ialyzer 25,000,000
left ventricular assist devices 100,000
Millions oflives saved. The quality ofLife improved for millions more.
A $100 billion industry
Figure 2. Common Medical Devices That Use Biomaterials
The development of biomaterials is the junction of materials science and
chemistry. Medical devices may be composed of a single biomaterial or a
combination of several materials. A heart valve might be fabricated from
polymers, metals, and carbons. A hip joint might be fabricated from metals
and polymers (and sometimes ceramics) and will be interfaced to the body
through a polymeric bone cement.
Biomaterials by themselves do not make a useful clinical therapy but rather
have to be fabricated into devices. This is typically an engineer's role, but the
engineer might work closely with synthetic chemists to optimize material
properties and with physicians to ensure the device is useful in clinical
applications.
Biomaterials must be compatible with the body, and there are often issues
that must be resolved before a product can be placed on the market and used
in a clinical setting. Because of this, biomaterials are usually subjected to the
same very stringent safety requirements as those of new drug therapies.
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Biomaterials for Biosensors
Implantable biosensors for the human body place some of the greatest functional
demands on biomaterials. Biosensors monitor the physiologic state of tissues for
medical therapeutics or for assessing human performance. Sensors for glucose, oxygen,
blood pH, adrenal hormones, nervous activity, heart performance, and blood pressure
monitors are all of interest.
Blood biochemistry sensors are the most difficult sensors to keep functioning over time
primarily because the sensor interface materials provoke low-level foreign-body
reactions in tissues. These types of responses are not specifically important to
implantable devices that have structural rather than sensing functions, such as heart
valves, but they can completely render a biosensor for blood glucose, for example,
useless after a few days.
Chemically sensitive biosensor interfaces to t