MASE 542/CHEM 442 BIOMATERIALS Spring 2012 Assoc. Prof. H. Funda Yagci Acar Koç University

Agenda Basic terminology/definition Types of materials regulations/players Types of materials Metals/Ceramics/Polymers Interaction of biomaterials with tissue Body response Testing Examples Student presentations

Examples Orthopedic Dental applications Ophtalmological applications Adhesives, sealants Sutures Drug delivery Diagnostics Cardiovascular Tissue engineering Breast implants

Grading 25% Midterm (March 28) 25% Project (abstract due April 2) 50% Final

Biomaterial…What? Medical devices include a broad range of products from simple tongue depressors to sophisticated programmable pacemakers with micro-chip technology. Medical devices include in vitro diagnostic products, such as general purpose lab equipment, reagents, and test kits, which may include monoclonal antibody technology. Certain electronic radiation emitting products with medical application and claims meet the definition of medical device. Examples include diagnostic ultrasound products, x-ray machines and medical lasers. About 50,000 substitute heart valves are implanted annually in the United States, and this number is also growing. At present, the leading mechanical valve design has been implanted in more than one million patients worldwide. In total, the prosthetics industry exceeds $10B annually and is expected to grow rapidly in the next few decades; the orthopedics industry alone has been growing steadily at 10% annually. Approximately 245,000 knee replacements are done annually in the United States, and this number is expected to grow rapidly as the population ages

Biomaterial…What? Medical devices include a broad range of products from simple tongue depressors to sophisticated programmable pacemakers with micro-chip technology. Medical devices include in vitro diagnostic products, such as general purpose lab equipment, reagents, and test kits, which may include monoclonal antibody technology. Certain electronic radiation emitting products with medical application and claims meet the definition of medical device. Examples include diagnostic ultrasound products, x-ray machines and medical lasers. About 50,000 substitute heart valves are implanted annually in the United States, and this number is also growing. At present, the leading mechanical valve design has been implanted in more than one million patients worldwide. In total, the prosthetics industry exceeds $10B annually and is expected to grow rapidly in the next few decades; the orthopedics industry alone has been growing steadily at 10% annually. Approximately 245,000 knee replacements are done annually in the United States, and this number is expected to grow rapidly as the population ages

Perfect mechine… Self-regulating process Feed back for internal balance Maintain equilibrium Continued disturbance – distructive response!

The Failing human machine Spare parts Bolts …… Improve quality of life Expand life-span

Biomaterial A (nonviable) material used in a (medical) device, intended to interact with biological systems (Williams, 1987) Any material of natural or of synthetic origin that comes in contact with tissue, blood or biological fluids, and intended for use in prosthetic, diagnostic, therapeutic or storage applications without adversely affecting the living organism and its components Nonviable: not capable of living If nonviable is removed we can also include many tissue engineering and artificial organs which use living cells Id medical is out we can include abroader range, biochip

Biomaterials Missirlis: A biomaterial is any material, single member of a generic class or a combination of two or more members out of the same or different classes, which can be used in a living body for a particular implant or group of implants, which does not incite negative response by the body, which is stable or exhibits only controlled and well-assessed breakdown.

Biocompatability Biocompatability is the ability of a material to perform with an appropriate host response in a specific application (Williams, 1987) When biomaterial in in contact with the living tissue it does not cause: harmful tissue reactions (pain, swelling or necrosis) causing a systemic toxic reaction having tumorigenic potential

Biomaterial Material Performance Bio-compatability www.qmed.com

Yes Bio but also material… understand the basic chemical and physical properties of materials determine the need for the application design your biomaterial “Declare the past, diagnose the present, foretell the future; practise these acts. As to diseases, make a habit of two things: to help, or at least to do no harm. The art has four factors, the disease, the patient, the physician and the engineer.” From the “Epidemics of the Hippocratic Corpus [4, p.165]” Need: mechanical strength, lifetime, degradation needed or not…size, shape…

Biomaterials Science Multidisciplinary: Multimaterial Need-driven Scientist, manufacturer, patient, physician, attorney! Multimaterial Need-driven Sustential market Risk-benefit

Material-Performance Metals Ceramics Polymers Composites Fibers, films, gels, foams, coatings, nanoparticles/nanotubes From Ratner, pg 2

Magnitute of the Field From Ratner, pg 3

Magnitute of the Field From Ratner, pg 3

75 million contact lense/ year worldwide 275 million hearth valves 500,000 total artificial hip and knee prostheses Size of the market and economics From Ratner, pg 3

Risk-benefit Cost/benefit, Cost/performance Pateients with diseased aortic heart valves: 50% chance of dying within 3 yrs Surgical replacement of the valve: 70% 10 years survival If good quality of life 60% of these patients will suffer from valve problems in 10 years. Cost of heart valve: 1000-4000$ Hospital bill: 60,000 $ About 10% requires replacement

Ethics

Regulations U.S. Food and Drug Administration (FDA) International Standards Organization (ISO): worldwide

Requirements of Biomaterials A biomaterial must be: inert or specifically interactive biocompatible mechanically and chemically stable or biodegradable processable (for manufacturability) nonthrombogenic (if blood-contacting) sterilizable

Bio-inertness vs. Bioactivity Bioactive materials have specific interactions with the surrounding tissue. Biocompatible material should affect the equilibrium of the body as little as possible Do stg ! Don`t do anything!

Biocompatability testing Determine potential toxicity resulting from contact of the biomaterial with the living tissue. materials should not—either directly or through the release of their material constituents—produce adverse local or systemic effects i.e. carcinogenic, adverse reproductive and developmental effects. Need systematic testing to ensure that the benefits >> potential risks Determine potential toxicity resulting from contact of the biomaterial with the living tissue. The device materials should not—either directly or through the release of their material constituents—produce adverse local or systemic effects, be carcinogenic, or produce adverse reproductive and developmental effects. Therefore, evaluation of any new device intended for human use requires data from systematic testing to ensure that the benefits provided by the final product will exceed any potential risks posed by device materials.

Classification of Medical Devices Based on the duration of the device use, invasiveness and risk to the user. Class I devices: minimal invasiveness, does not contact the user internally crutches, bedpans, tongue depressors, adhesive bandages etc. Class II devices: higher degree of invasiveness and risk, but relatively short duration. hearing aids, blood pumps, catheters, contact lens, electrodes etc. Class III devices: considerably more invasive and can pose immense risk to the user-implantables cardiac pacemakers, intrauterine devices, intraocular lenses, heart valves, orthopedic implants, etc.

UHDPE...used for base bath Polyester:fabric Polyurethane...pants MMA...bath tub

Commonly Used Biomaterials Applications Silicone rubber Catheters, tubing Dacron Vascular grafts Poly(methyl methacrylate) Intraocular lenses, bone cement Polyurethanes Catheters, pacemaker leads Stainless steel Orthopedic devices, stents Collagen (reprocessed) Cosmetic surgery, wound dressings DACROn: Du Pont PET Usually, they were not originally engineered for biomaterials applications !!!

How to choose the material? Application Properties Mechanical (ex., modulus) Chemical (ex., degradation) Optical (ex., whiteness, clarity) Structure

What governs materials choice? 1. Bulk properties: matched to those of natural organs 2. Ability to Process 3. Federal Regulations: FDA Rational design of biomaterials based on better understanding of natural materials and the material/biological organism interface

Example – Hip Implant With age or certain illnesses joints deteriorate. Particularly those with large loads (such as hip). Adapted from Materials Science and Engineering, Fig. 22.25, Callister 7e.

Example – Hip Implant Requirements mechanical strength (many cycles) good lubricity biocompatibility Adapted Materials Science and Engineering from Fig. 22.24, Callister 7e.

Example – Hip Implant Adapted from Fig. 22.26, Callister 7e.

Hip Implant Key problems to overcome fixation agent to hold acetabular cup cup lubrication material femoral stem – fixing agent (“glue”) must avoid any debris in cup Ball Acetabular Cup and Liner Femoral Stem Adapted from chapter-opening photograph, Chapter 22, Callister 7e.