MME 297: Lecture 03

Introduction[3] Introduction to Biomaterials: History and ethical issues

Dr. A. K. M. Bazlur RashidProfessor, Department of MME

BUET, Dhaka

• History of biomaterials

• Evolution of biomaterials field

• Ethical issues

Topics to discuss today ...

References:

1. Ratner et al, Biomaterials Science – An Introduction to Materials in Medicine, 3rd Ed, 2012.

pp: xxv iii-xxix, x li-liii, 1425-1431.

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HISTORY OF BIOMATERIALS

Canine metal implant1829

Artificial heart1881

Hip prostheses1956 Silicone contact lens

1829

Some historical examples

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[a] Before World War II

“Kennewick Man”, Kennewick, Washington, USA.

~9000 years old

• A tall, healthy, active person with a spear point embedded in his hip. It had apparently healed in, and did not significantly impede his activ ity.

• This unintended implant illustrates body’s capacity to deal with implanted foreign materials.

• The spear point has little resemblance to modern biomaterials, but it was a “tolerated” foreign material implant, just the same.

Tattoo~ 5000 years old

• Introduction of foreign material (carbon particles and other substances) into the skin

• Elicited a classic foreign-body reaction

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600 AD - nacre teeth from sea shells

200 AD - wrought iron dental implant in a corpse

• There was no materials science, biological understanding,

or medicine behind these procedures.

• Still, their success (and longevity) is impressive and highlights two points:

[1] the forgiving nature of the human body, and

[2] the pressing drive, even in prehistoric times, to address the loss of physiologic/ anatomic function with an implant.

SuturesLinen (early Egyptians)

Catgut (in the middle ages in Europe)Metallic sutures (Gold, Lead, Silver)

• Consider the problems that must have been experienced with sutures in eras with no

knowledge of sterilization, toxicology, immunological reaction to extraneous biological

materials, inflammation, and biodegradation.

shining nacre in sea shell

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Artificial Hearts and Organ Perfusion

1628 – English physician William Harvey wrote: “the heart’s one role is the transmission of the

blood and its propulsion, by means of the arteries, to the extremities everywhere.”

1812 – French physiologist Le Gallois expressed: “organs could be kept alive by pumping blood through them”

1881 - Étienne-Jules Marey published and invented in photographic technology, motion studies, and physiology, described an artificial heart device (Figure 1) to studying the

beating of the heart.

1938 - Charles Lindbergh and Alex is Carrel wrote a book, “The Culture of Organs” addressing issues of pump design (referred to as the Lindbergh pump), sterility, blood damage,

the nutritional needs of perfused organs, and mechanics.

1950 - Dr. Paul Winchell patented an artificial heart.

1957 - Dr. Willem Kolff and a team of scientists tested the artificial heart in animals.

Contact Lenses

1508 - Leonardo Da Vinci developed the concept of contact lenses

1632 - Rene Descartes is credited with the idea of the corneal contact lens1827 - Sir John F. W. Herschel suggested that a glass lens could protect the eye1860 - Adolf Gaston Eugen Fick invented the first contact lens offering real success

1936 – 1948: Plastic contact lenses were developed, primarily of PMMA 6/24

1829: H.S. Levert studies canine responses to implanted metals “in vivo”

1870: British surgeon Joseph Lester introduces aseptic surgical techniques

(“asceptic” – free from contamination by harmful bacteria, viruses or other microorganisms)

1886: German doctor H. Hansmann first used metal plates for internal fixation

1931: Boston surgeon Smith Peterson develops a metal cup for partial hip implants

1939 – 1945: WWII spurs the development of many new materials and

orthopaedic surgical techniques.

(Up until ~1950, mostly metals were used because very few plastics existed)

1947: First paper on polyethylene as a synthetic implant material

1949: Paper published about plastics “sweating out” additives, resulting in a strong

(negative) biological reaction.

Important dates in biomaterials history

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[B] Post World War II - chaos reigns in the biomaterials world !!

• High-performance metal, ceramic, and especially polymeric materials newly

developed during World War II, and particularly at the end of the war, were

transitioned from wartime restriction to peacetime availability.

• Materials, originally manufactured for airplanes, automobiles, clocks, and radios

were taken “off-the-shelf” by surgeons and applied to medical problems.

• These early biomaterials included silicones, polyurethanes, Teflon®, nylon,

methacrylates, titanium, and stainless steel.

surgeons did not collaborate with scientists or engineers

surgeon hero! – dentists/doctors would invent “on the fly”

when patients’ lives or functionality were at stake

minimal government regulatory activity

Almost 20 years of unmonitored work !8/24

[c] 1950 - present: a Biomaterials Revolution

1962 : Drug Amendments and Consumer Bill of Rights passages

• The “quantum leap” in recent decades, enabled by increasingly better

laboratory technologies (e.g., fluorescence microscopy), is the

understanding of biocompatibility on a cellular and molecular level

• Before 1950, this lack of understanding translated to a very low implant

success rate due to rejection by the immune system

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Intraocular lens (IOL)

1949 - Sir Harold Ridley, MD

Hip and Knee Prostheses

1961 - John Charnley invented the first really successful hip joint prosthesis

1968 - Frank Gunston and John Insall made first successful total knee replacement

Dental Implants

1809 - Gold post anchor for tooth

1887 - Platinum post anchor for tooth

1937 - Surgical Vitallium (Co–Ni alloy) and Co–Cr–Mo alloy

1952 - Ti and its alloy

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Artificial Kidney1960 - Willem Kolff developed a “washing machine artificial kidney” dialyzer system

1962 - Dr. Belding Scribner and Wayne Quinton devised a method made of Teflon

and silicone to routinely access the bloodstream for dialysis treatments

The Artificial Heart1960 - Willem Kolff implanted the first artificial heart made of PVC in a dog

1953 - John Gibbon invented the heart-lung machine

1966 - Dr. Michael DeBakey implanted a left ventricular assist device in a human

1969 - Dr. Denton Cooley and Dr. William Hall implanted

a polyurethane total artificial heart

Stents1983 - Dr. Julio Palmaz invented of the coronary artery stent made of SS wire

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Year Investigator s Development

Late 18th –

19th century

Various metal devices to fix bone fractures;

wires and pins from Fe, Au, Ag, and Pt

1860–1870 J. Lister Aseptic surgical techniques

1886 H. Hansmann Ni-plated steel bone fracture plate

1893–1912 W.A. Lane Steel screws and plates (Lane fracture plate)

1912 W.D. Sherman Vanadium steel plates, first developed for medical use;

lesser stress concentration and corrosion (Sherman plate)

1924 A.A. Zierold Introduced Stellites® (Co-Cr-Mo alloy)

1926 M.Z. Lange Introduced 18-8-Mo stainless steel, better than 18-8 stainless steel

1926 E.W. Hey-Groves Used carpenter’s screw for femoral neck fracture

1931 M.N. Smith-Petersen First femoral neck fracture fix ation device made of stainless steel

1936 C.S. Venable, W.G. Stuck Introduced Vitallium® (19-9 SS), later changed the material to CoCr alloys

1938 P. Wiles First total hip replacement prosthesis

1939 J.C. Burch, H.M. Carney Introduced tantalum (Ta)

1946 J. and R. Judet First biomechanically designed femoral head replacement prosthesis;

first plastics (PMMA) used in joint replacements

1940s M.J. Dorzee, A. Franceschetti First used acrylics (PMMA) for corneal replacement

1947 J. Cotton Introduced Ti and its alloys

1952 A.B. Voorhees, A. Jaretzta,

A.B. Blackmore

First successful blood vessel replacement made of cloth for tissue ingrowth

1958 S. Furman, G. Robinson First successful direct heart stimulation

1958 J. Charnley First use of acrylic bone cement in total hip replacement

1960 A. Starr, M.L. Edwards First commercial heart valves

1970s W.J. Kolff Total heart replacement

1990s Refined implants allowing bony ingrowth

1990s Controversy over silicone mammary implants

2000s Tissue engineering

EVOLUTION OF BIOMATERIALS FIELD

• Biomaterials research and development have been stimulated and

guided by advances in cell and molecular biology, chemistry,

materials science, and engineering.

• The biomaterials community has been the major contributor to the

understanding of the interactions of materials with the physiological

environment (often referred to as the biointerface).

• The development of biomaterials for medical and dental applications

has evolved through three generations, each somewhat

temporally overlapping, yet each with a distinct objective (Figure 2).

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First Generation

Goal: Bio inertness

minimal reaction/interaction

2020

2000

1980

1960

1940

FIGURE 2. Evolution of biomaterials science and technology

• The goal of early biomaterials (first generation) was to achieve a suitable

combination of functional properties to adequately match those of the replaced

tissue w ithout deleterious response by the host.

• Dev eloped in 1950s and 1960s, they comprised largely of off-the-shelf, widely

av ailable industrial materials that w ere not developed specifically for medical use.

• Selected because of the desirable combination of physical properties specific to

the intended clinical use, and because they were bio-inert, and therefore they

w ere considered biocompatible.

• Ex amples: elastomeric polymer, silicone rubber, pyrolytic carbon.

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2020

2000

1980

1960

1940

• Second generation biomaterials evolved from those early biomaterials.

• Bio-active materials - intended to elicit a controlled reaction with the tissues

into w hich they were implanted in order to induce a desired therapeutic effect.

• Ex amples: bioactive glasses and ceramics for orthopedic and dental surgeries;

in controlled localized drug release applications; in cardiac assist device; drug-eluting endov ascular stents in balloon angioplasty.

• Dev elopment of resorbable biomaterials, with rates of degradation

that could be tailored to the requirements of a desired application.

• Ex amples: biodegradable suture composed of polyglycolic acid (PGA)

Second Generation

Goal: Bio activity

resorbable biomaterials; controlled

reaction with the physiological

environment (e.g., bone bonding, drug release)

FIGURE 2. Evolution of biomaterials science and technology15/24

Third Generation

Goal: Regenerate functional tissue

biointeractive, integrative, resorbable;

simulate specific cell responses at the molecular level

(e.g., proliferation, differentiation)

2020

2000

1980

1960

1940

• The third generation of biomaterials, the logical extension of the rapidly

progressing state-of-the-art, has the goal of supporting and stimulating

the regeneration of functional tissue.

• With adv ances in tissue engineering and regenerative medicine,

true replacement w ith living tissue becomes possible and biomaterials play a key role in tissue engineering and regenerative therapeutics.

• Ex amples: bioresorbablepolymer for porous scaffolds

FIGURE 2. Evolution of biomaterials science and technology16/24

FIGURE 3 The tissue engineering paradigm – various cell types are seeded on porous scaffolds, possibly

proliferated in a bioreactor, and finally implanted in various tissue sites to restore or regenerate damaged

or missing tissue. (nature.com.)

• Implantation in hundreds of thousands of patients with good success is noted.

• A broad range of synthetic materials of varying properties are used.

• Most anatomical sites can be interfaced with a device.

• The normal response by which the body responds to foreign bodies is observed.

• Problems, concerns, unexplained observations or unintended consequences

may be noted for each device.

• Most device complications are related to biomaterials–tissue interactions.

• Companies are manufacturing devices and bringing value to shareholders (and patients).

• Regulatory agencies are carefully assessing device performance , and making policy

decisions to monitor the device industry, ensure quality, and protect the patient.

• Ethical and societal issues are associated with each device.

To summarise:

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ETHICAL ISSUES

Ethics is the branch of philosophy that addresses questions

of morality.

Biomedical ethics, therefore, focus onto the morality judgments

that must be made in the field of medicine, and its allied

subjects including biomaterial science.

Questions of morality have direct relevance to the practical

work of scientists and clinicians in the field.

There is also increasing public scrutiny of biomedical science

in general.

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Ethical Principles for Medical Practices

1. beneficence (benefiting patients),

2. non-maleficence (doing not harm),

3. patient autonomy (the right to choose or refuse treatment),

4. justice (the equitable allocation of scarce health resources),

5. dignity (dignified treatment of patients),

6. confidentiality (of medical information) and

7. informed consent (consent to treatment based on a proper

understanding of the facts)

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Human Enhancement

• Whereas the devices and techniques developed by biomedical engineers are

usually designed to support therapy or diagnosis, they may also be designed

to enhance healthy human traits beyond a normal level .

• This is called human enhancement, and it is morally controversial

because it moves traits beyond boundaries of the human species, and therefore

has the potential to create superhumans.

• If medicine were to engage in human enhancement, it would move beyond its

traditional mission, which is merely curative and preventive.

• Enhancement may even require the impairment of healthy human tissue or

organs to fit augmentations.

• It therefore remains controversial whether biomedical engineers (and medical

practitioners) should engage in human enhancement.

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The paramount ethical principle in biomaterial research

is the protection of patients.

With this goal in mind, FDA has established a set of regulatory guidelines

to standardize studies related to medical devices.

As a result, scientific investigation into the development of medical devices must

be performed in accordance with defined best practice standards, which carry

the weight of law:

• Preclinical studies must use Good Laboratory Practice (GLP)

• Manufacture of devices must follow Good Manufacturing Practice (GMP)

• Clinical trials must be in compliance with Good Clinical Practice (GCP)

These Good Practice guidelines are quality systems concerned with organizational

processes that are founded upon ethical principles and ensure accountability at

every level from the designers, the manufacturers, and the investigators.

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• GLP is a quality system that ensures the integrity and quality of data supporting the approval

and eventual manufacture of a regulated medical dev ice.

• It includes compliant organization and management, a defined study plan, defined standard

operating procedures, suitable facilities and material, documentation and archiv ing of results, as well as an independent quality assurance program.

• Personnel at every level of the study must understand how their role in the research is

conducted within GLP regulations.

• GMP, constitutes a series of quality system requirements that govern the methods, the

facilities, and the controls used by manufacturers, processors, and packagers of medical devices intended for human use.

• It ensures that all finished products are safe and in compliance with the FDA.

• GCP protects the rights of human subjects participating in clinical trials consistent with

ethical principles, and ensures the integrity of clinical research data.

• Therefore, GCP defines a standard for clinical practices which encompasses the design,

conduct, monitoring, termination, audit, analysis, documentation, and reporting of the studies and which ensures that the studies are scientifically and ethically sound, and that the clinical properties of the product

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Next Class

MME 297 Lecture 04

Structure-Property Correlation[1] Structure-properties-processing-performance relation