RYERSON UNIVERSITY FACULTY OF ENGINEERING, ARCHITECTURE & SCIENCE DEPARTMENT OF CHEMICAL ENGINEERING

CE8603 Advances in Biomaterials

Introduction to Biomaterials
By: Yaser Dahman

Lecture One Winter, 2012

Lecture Content
Biomedical engineering Definition of biomaterials Applications of biomaterials History of biomaterials Biocompatibility of biomaterials Ethical issues R Regulations l ti Testing and approval Future directions

Biomedical Engineering (BME)

The application of engineering principles and techniques to the medical field. It combines the design and problem solving skills of engineering with the medical and biological science to help improve patient health care and the quality of life of healthy individuals Consists of research and development, covering an array of fields: bioinformatics, medical imaging, image processing, physiological signal processing, biomechanics, biomaterials and bioengineering, systems analysis, 3-D modeling, etc. It is an exciting field of science, experiencing steady and strong growth over its history with companies such as Smith and Nephew investing large amounts of money in new products. Biomaterials science encompasses elements of medicine, biology, chemistry and materials science.

Definition of Biomaterials
A biomaterial is any material, natural or man-made, that comprises p whole or p part of a living g structure or biomedical device which performs, auguments, or replaces a natural function

A biomaterial is a nonviable material used in a medical device, intended to interact with biological systems The definition of a biomaterial does not just include manmade materials which are constructed of metals or ceramics. A biomaterial can also be an autograft, allograft or xenograft used as a transplant material

Biomaterials
Can also refer to

Biological matter Biocompatible material and bio-applicable material Biologically derived material (or biotic material) Bio-based material

History of Biomaterials
Adolf Fick invented the contact lens in 1860, probably the first one to offer real success. By 1929 Vitallium alloy was developed and used with success in dentistry. In 1938, P Wiles performed the first total hip replacement. In the 1940s M.J.Dorzee and A. Franceschetti, used acrylics for corneal replacement. In 1944, W.H.Kolff invented the first hemodialyzer. On Nov 29, 1949, the first implantation in the human took place (modern artificial heart pump) In 1958 S.Forman S Forman & G. G Robinson performed the first successful direct stimulation of heart. In 1960, A.Starr & M.L.Edwards invented the first artificial heart valve. During the 1980s, W.J.Kolff and other scientists invented the first artificial heart.

Integral Subjects
Toxicology Biocompatibility Functional Tissue structure and pathobiology Healing Dependence on Specific anatomical sites of implantation Mechanical and Performance requirements Industrial involvement Ethics Regulation

Biocompatibility
the ability of a material to perform with an appropriate host response in a specific application. application Williams Williams' definition. definition the quality of not having toxic or injurious effects on biological systems. comparison of the tissue response produced through the close association of the implanted candidate material to its implant site within the host animal to that tissue response recognized and established as suitable with control materials- ASTM

Biocompatibility Implantable
medical device
long-term: the ability of the device to perform its intended function short-term: the ability of the device to carry out its intended function with minimal interaction between device and blood Tissue-engineering products: the ability to perform as a substrate that will support the appropriate cellular activity

Biocompatiblization
Biocompatible materials are intended to interface with biological systems to evaluate, treat, augment or replace any tissue, organ or of the body. Biomaterials are usually y non-viable, but may y also be viable. A biocompatible material is different from a biological material such as bone that is produced by a biological system. Artificial hips, , artificial pacemakers, and catheters are all made from different biomaterials and comprise different medical devices. Biomimetic materials are not made by living organisms but have compositions and properties similar to those made by living organisms. The calcium hydroxylapatite coating found on many artificial hips is used as a bone replacement that allows for easier attachment of the implant to the living bone. Surface functionalization may provide a way to transform a bio-inert bio inert material into a biomimetic or even bioactive material by coupling of protein layers to the surface, or coating the surface with self-assembling peptide scaffolds to lend bioactivity and/or cell attachment 3-D matrix. Different approaches to functionalization of biomaterials exist. Plasma processing has been successfully applied to chemically inert materials like polymers or silicon to graft various functional groups to the surface of the implant. Polyanhydrides are polymers successfully used as a drug delivery materials.

Bigger Picture
An implant is a medical device made to replace and act as a missing biological structure (as compared with a transplant, which indicates transplanted biomedical tissue). A medical device is an instrument, apparatus, implement, machine, contrivance, implant, in vitro it reagent. t

Testing (Ethical Issues)

material in a given application, and thus medical devices such as implants or drug delivery devices

in vitro: in accordance with ISO10993 to determine if a certain material (or rather biomedical product) is biocompatible in vivo: Animal testing; Clinical trials

Animal experimentation
Animal experimentation is the first step in introducing a biomaterial. Animal experimentation precedes clinical trials. The main question boils down to this: Should animals be treated on the same level as humans? There are several criteria which scientists use to determine the level of treatment an animal has the right to. The criteria include: Intelligence, ability to feel pain, and pleasure, social interaction in a given species, resemblance to humans, position on the evolution ladder and whether particular animals have been pets.

Clinical Trials
Clinical trials are a way of testing a hypothesis, drug or biomaterial by using humans as subjects. Clinical trials are beneficial because they provide the answers required by the biomaterial scientist. Usually a human subjects review committee will supervise the planning process to ensure adherence to ethical standards. Researching humans should be conducted to minimize risk to the patient and offer a reasonable risk-to-benefit ratio.

Regulation
Biomaterials need to be regulated in order to ensure the safety of its users. Various regulatory bodies exist to prevent unsafe products and unqualified people from selling various biomaterials. For example the government of United States has a regulatory system administered by the US Food and Drug administration (FDA). Most nations also have their own regulatory bodies. However international regulatory body also exists. The International Standards Organization (ISO) has introduced international standards for the world community.

Device Failure
Nothing is perfect, especially man-made objects. There are many y causes for the failure of the specific p biomaterial.

1) 2) 3) 4) 5)

Inadequate materials testing. Design flaw. Errors during fabrication Damage or contamination during implantation. Abnormal patient response to the biomaterial

Biomaterial Applications
Joint replacements Bone plates Bone cement Artificial ligaments and tendons Dental implants for tooth fixation Blood vessel prostheses Heart valves Skin repair devices Cochlear replacements Contact lenses

Cardiovascular Devices
Diseases of the cardiovascular system contribute to about 20% of the fatality in older people p p Diseased blood vessels and inefficient heart valves are routinely replaced with natural tissues or synthetic materials including natural or synthetic polymers Cardiac pacemaker Pacemaker is the tool, which controls the pace of the heart. The normal heart is contracted by an electrical event. event Therefore, an implanted pacemaker performs the same function. The pacemaker consists of conducting electrodes attached to lead consisting of a connector and a pulse generator. The maximum lifetime of the pacemaker is less than 10 years.

Technology EvolutionEvolution-Stents
Cardiovascular Stents:
Metal cage used in balloon angioplasty In-stent restenosisnatural healing response Coated metal with Paclitaxel drug Axcel stent eliminates metal

Patent pending Wire

Boston Scientific/Cook
Propping open arteries more effective than balloon Re-narrowing of blood vessel, clotting & reaction to metal

Angiotech
Dialing in optimal amount of controlled scarring

Axcelon
Microbial cellulose vascular graft shows minimal clotting in rats

Artificial Blood Vessels for Microsurgery

Klemm et al. Prog Polym Sci., 26:1561 (2001)

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Extracorporeal Devices
Artificial Kidneys Upon failure of the biological kidneys, the patient patients s blood must be treated on the artificial kidney (haemodialysis, for 4 to 5 hours per treatment, 3 days a week) Artificial kidney has become the most successful artificial organ, able to support large number of patients. Artificial kidney can partially stimulate the biological kidney by removing nitrogenous metabolic waste products, such as urea urea, uric acid and creatinine. creatinine A typical dialyzer consists of a membrane bath and a pump to circulate blood from the artery and return the clean blood to the vein.

Ophthalmology
Contact lenses Contact lenses are very widely used. used They are used for both cosmetic and health related reasons. They can be used to improve the appearance of damaged eyes and to change or enhance eye colour. The desired properties for the contact lenses are: high oxygen permeability, resistance to d deposition iti of f protein, t i mucus, li lipid, id micro-organisms and other foreign substances.

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Ophthalmology
Intraocular lenses An intraocular lens is an implanted p lens in the eye. y The main function is to change the optical power of the eye. They consist of an optic portion through which light passes and attachment regions. The optical portion is composed of PMMA: however other polymers such as PHEMA and silicone have also been used.

Orthopedics
The skeleton has numerous functions, but the one which accounts predominantly for its shape, mass and material properties are the requirements that it should bear load. Orthopedic implants need a thorough analysis of stress fields. All the mechanical properties come i t play. into l An A example l is i Joint J i t replacement.

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Joint Replacement
Synovial joints are mobile joints, which include human hip, p, knee, , elbow, , ankle, , finger and shoulder joints. Many older people are subjected to degenerative bone and joint diseases such as osteoarthritis and rheumatoid arthritis. Theses diseases necessitate joint replacements. Theses diseases necessitate joint replacements. l t The Th materials t i l used di in j joint i t replacements include: metals, Ceramics and polymers.

Joint Surface Replacement

Wound Dressing Applications

0 days

3 days

High moisture retention and high fluid absorption promotes healing by protecting chronic wounds from infection and maintain moisture levels in the wound

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Future Directions
Biomaterial is expanding at a faster rate than ever. The impacted population grows at over 10% per year. Worldwide, first-year and follow-up costs of organ replacement and prostheses exceeds $300 billion US dollars per year and represents between 7% and 8% of total worldwide healthcare spending. People will always be in need of biomaterials.

Functions
Tissue replacement with synthetic is achieved by selecting the material that has physical properties most similar to those of natural tissues. Implants: groups of materials that is used for surgical applications are: Metal, alloys, ceramics, polymers, and composites. Hard Tissue: rigid materials are used to replace bone and dentin. Soft Tissue: soft materials are used for soft tissue reconstructions.

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Surgical Implants
The wound and burn dressing Total knee or hip p replacement: p composites p of metal, ,p polymer y and ceramic Ophthalmology implants : lens implants, corneal transplants. Facial implants: cosmetic reason (reconstructive) Oral implants: artificial teeth or dentures and oral cavities Vascular grafts: replacement of the aorta, diseased heart valves, bypassing blocked coronary arteries. Surgical tapes and tissue adhesives adhesives.

Biomaterials Origins
Metal and alloys Ceramics Polymers Composites

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Metals and Alloys

Main alloys are titanium-aluminium, stainless steel and cobalt-chromium Used universally for most of the high load bearing applications in skeletal system Conducting metals (platinum and platinum-iridium alloys) are used for electrical stimulation of the heart, muscles, and nerves tissues Nitinol, an alloy of nickel and titanium are used in orthodontics.

Ceramics
Alumina is an extremely stable and inert ceramic materials used in orthopedic joint replacement Degradable ceramics are used in hard tissue regeneration Inert carbons are used in cardiovascular applications in addition to dental applications.

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Polymers
Soft tissue replacement: skin, tendons, cartilage, vessel walls, lens, breast and bladder. Also used as sutures, tissue adhesives, shunts, catheters, h and d space fillers fill Includes: polyolefins, polyamides, polyesters, polyurethanes, polyacrylates, polysulfones, polyethers, and silicone rubber Biodegradable polymers (natural and synthetic polyesters, polyamides) are used as biodegradable sutures or as bone plates that provide temporary scaffolding or support while natural tissue regeneration takes place. This is in addition to drug delivery applications Collagen polymers (natural polymers) are used for replacement of arterial wall, heart valves, and skin Membranes are used in the extracorporeal devices (dialyses and oxygenators).

Composites
Consists of two or more phases with good interfacial bonds between phases Composites: simple blends, IPN (partial and full), particles and fibers reinforcements Control over bulk and surface properties Mechanical properties are altered compared to the homogenous constituents Properties depend upon the volume fraction, the shape of the heterogeneities and the interfacial binding Many natural tissues are in face composite materials

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Testing and Failure

Standard engineering testing machines are used to obtain data on bone specimens or soft tissues in simple elongation Failure in biological sense: yielding, plastic deformation, creep, rupture, fatigue, corrosion, wear and impact fracture. To study strength of biological materials, one has to correlate clinical observation and pathological lesions with stress and strain in the tissues.

Tissue Response

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Long-Term Performance

Engineering Factors

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Tissue Engineering
Concepts of growth and change lead to the proposal of tissue engineering Objective: to produce the necessary structural and mechanical properties required to fulfill the physiological function Tissue Engineering: the application of the principles of engineering and biology towards a fundamental understanding of the structure-function relationship of tissues and the development of biological substitute.

Tissue Engineering

Allows to grow tissue type as opposed to implanting bioinert materials that only mimic the shape of living tissue and provide mechanical support.

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Regenerative Medicine

Regenerative Medicine is the process of creating living, functional tissues to repair or replace tissue or organ function lost due to age, disease, damage, or congenital defects.

Applications
Materials that blocks unwanted reactions p between transplanted cells and host tissue Polymer-cell composites for patching injured tissues Expanding p g therapeutic p cells in culture and in growing relatively simple tissues.

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 The laboratory grown skin to replace grafts Bone marrow cells recovered before chemotherapy are being multiplied in culture Cultured liver cells are used to detoxify blood from patients with liver failure Artificial blood vessels covered with the patients own endothelial cells

Growing Humans Ear

Dr. Charles Vacanti of the University of Massachusetts grew a human ear on the back of a mouse with the assistance of Dr. Linda Griffith Cima from MIT. Griffith-Cima MIT The study was done at the suggestion of a plastic surgeon who was interested in developing techniques for attaching ears in children who had external ear deformities or had lost ears in accidents. It was designed to serves as a model for tissue engineering.

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