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

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Prepared by: Acquisition Support Division (DW0-3) Defense Warning Office Directorate for Analysis Defense Intelligence Agency 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,

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Importance of Biocompatibility .........................................................................vii Science of Biomaterials .....................................................................................vii Biomaterials for Biosensors ................................................................................... 1 Biomaterials for Biomedicine ................................................................................. 2 Silicone Chemistry.............................................................................................. 4 Silicone in Biomedical Products.......................................................................... 4 Biodegradable Polymers..................................................................................... 7 Polylactic Acid and Polyglycolic Acid .................................................................. 8 Polyethylene Glycol or Polyethylene Oxide....................................................... 10 Titanium - Hip and Knee Joints ........................................................................ 11 Tissue Constructs as Biomaterials ...................................................................... 13 Cardiovascular Biomaterials............................................................................. 15 Stent Biomaterials............................................................................................ 18 Drug Delivery Polymers.................................................................................... 20 Medical Titanium as a Biomaterial.................................................................... 22

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Biomaterials in Dialysis .................................................................................... 24 Summary and Recommendations ......................................................................... 25 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 7. Silicone Sheets Used Under the Skin as a Physical Supporting Layer for Repair of Scar Tissue ............................................................................... 5 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 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 Figure 17. Bioceramic Used in Artificial Hip Replacement Component.................. 12 Figure 18. Computer-Based Sculpted Ceramic Teeth ............................................ 13 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 27. Contact Lens........................................................................................ 20 Figure 28. Schematic Representation of Biodegradable (Bioerodible) Drug 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 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 Hip j int tifi ial heart 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 UNCLASSIFIED//FOR OFFICIAL USE ONLY

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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