Biomaterials (Structure & Applications)

Submitted to:

Sir Zafar Shakoor

Submitted by:

Usama Waheed

Subject:

Engineering Materials

Program:

BSc Chemical Engineering

Semester:

Second (2nd)

Date:

22/4/2017

Roll no:

16103123-032
 Table of Contents
Contents
Biomaterials: ........................................................................................................................................... 3
Evaluation of materials behaviour: ......................................................................................................... 3
Implant-associated infection: ................................................................................................................. 3
Applications of Biomaterials: .................................................................................................................. 5
Cardiovascular medical devices: ............................................................................................................. 5
Tissue engineering scaffolds: .................................................................................................................. 6
Ophthalmologic applications: ................................................................................................................. 6
Bio-electrodes and biosensors:............................................................................................................... 6
Burn dressing and skin substitutes: ........................................................................................................ 7
Sutures: ................................................................................................................................................... 7
Drug delivery systems (DDS): .................................................................................................................. 7
Dental materials: ..................................................................................................................................... 8
Conventional acid-base cements: ........................................................................................................ 9
Poly-electrolyte cements: Zinc poly carboxylates and glass ionomers : ............................................. 9
Resin-modified glass-ionomer cements .............................................................................................. 9
Dual-setting resin-based cements........................................................................................................ 9
Reference: ............................................................................................................................................. 10
Biomaterials:

A biomaterial is any substance that has been engineered to interact with biological systems
for a medical purpose - either a therapeutic (treat, augment, repair or replace a tissue function
of the body) or a diagnostic one. As a science, biomaterials is about fifty years old. The study
of biomaterials is called biomaterials science or biomaterials engineering. It has experienced
steady and strong growth over its history, with many companies investing large amounts of
money into the development of new products. Biomaterials science encompasses elements of
medicine, biology, chemistry, tissue engineering and materials science.

Note that a biomaterial is different from a biological material, such as bone, that is produced
by a biological system. Additionally, care should be exercised in defining a biomaterial as
biocompatible, since it is application-specific. A biomaterial that is biocompatible or suitable
for one application may not be biocompatible in another.

Biomaterials can be derived either from nature or synthesized in the laboratory using a
variety of chemical approaches utilizing metallic components, polymers, ceramics or
composite materials. They are often used and/or adapted for a medical application, and thus
comprises whole or part of a living structure or biomedical device which performs, augments,
or replaces a natural function. Such functions may be relatively passive, like being used for a
heart valve, or may be bioactive with a more interactive functionality such as hydroxy-apatite
coated hip implants. Biomaterials are also used every day in dental applications, surgery, and
drug delivery. For example, a construct with impregnated pharmaceutical products can be
placed into the body, which permits the prolonged release of a drug over an extended period
of time. A biomaterial may also be an auto-graft, allograft or xeno-graft used as a transplant
material.

Evaluation of materials behaviour:

Prior to clinical use of any substance (biomaterial or drug), which is going to be in contact
with our organism, it should be strictly tested and proven to be non-hazardous for us. Those
processes to examine this biomaterial can be classified in 3 parts. First requirement is the
matching physical and chemical properties of the substance, desired to be the same or at least
compatible with the organism. These materials, therefore, are produced according the tissue
features, where they are going to be used. According to tissue type; physical strengths
(tensile, compressive, shear strength, elasticity modulus), thermal properties, photo-reactivity
or translucency, colour, calcification potency, surface structure, chemical features, or
degradation resistance are modified for ideal adaptation to the environment. Those features
are examined under laboratory conditions before biologic behavioural tests.

Implant-associated infection:

A material or object placed in to an organism to restore a function, mass loss or to measure,

diagnose or treat any condition is called as “implant”. Implants’ success is directly related to
their survival. Life expectancy of the implants can be interfered with several endogenous or
exogenous factors. Least but not the last issue considering implant failure is the infection.
Implant, as a foreign material has a risk to undergo rejection. Therefore; implants are
produced of biocompatible materials and sterilized before placement into the body. As
antimicrobial body protection is carried out by our skin and mucosal barrier, inner
environment of the body is sterile, except some parts like digestive system canal etc.
Microorganisms are always in contact with this shield and are not let go inside. However, any
kind of injury may break the integrity of the skin-mucosa barrier and can open a gate to the
microorganisms to enter body. Following their entry, they replicate themselves and retain at a
weak part of organism (colonization). During the proliferation process the also synthesize and
release some toxins to damage the host to weaken its defence or to make the environment
more proper for their survival. Inoculation of microorganism to the implant material can be
via direct contact or blood stream can act like a high-way to transport the microorganisms
from a distant entry point to the implant. Either way of exposure can easily initiate
colonization of the microorganisms on the implant, in other words infection. Implant, itself,
has a risk of rejection and invasion by the microorganisms would lead and hasten withdrawal
of the implant. Especially mouth, as a wet and warm atmosphere full of food debris, is an
ideal environment for bacteria colonization.

That makes it a unique part of the body, with the highest type multiplicity of microorganism
and highest microorganism concentration in one unit of saliva. Those factors mentioned
above increase the infection risk of dental implants placed in edentulous jaw bones to restore
chewing, phonation functions and aesthetic. Implant surface roughened intentionally to
increase bone-implant contact area for more stability and longer survival in the bone cavity.
Rough surface provide an ideal environment for bacteria colonization with its retentive
topography and can facilitate increase of bacteria count on dental implant. Moreover;
incidence of dental implant placement is the higher than all other types of implants. This high
frequency of application also increases the infection coincidence of dental implants. Dental
implant infections can be as high as 31.2%

Overcoming implant associated infections is another focus of current researches. Previous

efforts focused on killing already-colonized microorganisms via several antimicrobial agents
like antibiotics or debriding the colonies with several techniques like scratching, chemical
cautery or damaging the colonies via photo thermal effect of laser energy. However current
concepts have centred on prevention of colonization or may be killing the microorganism as
they contact the implant. Those studies showing positive effect of antibiotic use on infection
treatment grounded the idea of keeping antibacterial agents around the implant site during
healing process. Initial attempts aimed administration of antimicrobials, like tetracycline,
ciprofloxacin, vancomycin, rifampin/minocyclin, cefoperazone, penicillin/streptomycin,
gentamicin, around the implant to prevent infection. However; those local administration of
antibiotics to the implant site topically had limited release time and couldn’t prevent
development of infection in long term. Idea of gradual release of the antimicrobial substances
by the implant has leaded coating titanium surface with antibiotics with restricted success
limited time of degradation process of antimicrobial drug coating [80]. Several local drug
delivery vehicles like (glycolic, lactic acid, caprolactone, methyl methacrylate polymers,
chitosan, agarose/hydro-gels, bioactive ceramics, collagen, nanotubes), have been studied to
prolong releasing period of the antibiotic. Choice of delivery medium is dependent on:

1. Type of tissue to be placed (whether soft tissue or bone)

2. Environment of the implant to be protected (mouth, skin, bone, vessels, heart, genitor-
urinary system, aero digestive system, cranium or any place inside the body)
3. Required releasing time (slow or fast)

4. Biodegradation mechanism

5. How many drugs will be used (single or multiple) and

6. Compatibility with antimicrobial agent to be sustained.

Simultaneously; antimicrobial prevention concepts have evolved innovative surface

technologies based on the knowledge that certain metal ions like silver, copper, bismuth and
zinc have oligo-dynamic effect (toxic effect on living organisms) on microorganisms. Target
of those researches centred on modifying the titanium dental implant surface with these
above mentioned metal ions to wall-up a defensive line on the titanium surface and protect
themselves against bacterial attacks. Similarly zirconium doped titanium presents
antimicrobial activity beside high epithelial cell attraction and mediate healthy cell
proliferation to promote formation epithelial cell barrier over the implant surface.

Development of carbon-nanotube systems grown on implant surface can give the capability
of controlled release of any drug implanted. It has been shown that they can act as sensing
probe for various (electrical, thermal, photo or chemical) stimuli. These triggering factors can
be redox reactions of bone-forming cells (osteoblasts) or connective tissue-forming cells
(fibroblasts) or any substance specifically released from bacterial wall. As impulses are
sensed, such materials can release any given drugs to potentially fight bacterial infection,
reduce inflammation, promote bone growth or reduce fibroblast functions.

Applications of Biomaterials:
The main applications of biomaterials can be classified into the categories below and described later:
•Cardiovascular medical devices (stents, grafts and etc.)

•Ortho-pedic and dental applications (implants, tissue engineered scaffolds and etc.)

•Ophthalmologic applications (contact lenses, retinal prostheses and etc.)

•Bio-electrodes and biosensors

•Burn dressings and skin substitutes

•Sutures

•Drug delivery systems

Cardiovascular medical devices:

Heart valves, endovascular stents, vascular grafts, stent grafts and other cardiovascular grafts are
common medical devices in cardiovascular applications. There are several major forms of valvular
heart disease, most involving the aortic and/or the mitral valve. The most common type of valve
disease and most frequent indication for valve replacement overall is calcific aortic stenosis
obstruction at the aortic valve secondary to age-related calcification of the cusps of a valve that was
previously anatomically normal. In case of vascular pathologies, stents and vascular graft is used.
Different polymers and metals with or without coating can be applied in this category (titanium,
poly-tetra-fluoro-ethylene and etc.

Tissue engineering scaffolds:

Tissue engineering is one of the most important ways to achieve tissues for repair or replacement
applications. Its goal is to design and fabricate reproducible, bioactive and bio-re-absorbable 3D
scaffolds with tailored properties that are able to maintain their structure and integrity for
predictable times, even under load-bearing conditions. Scaffolds can be applied in different tissues.
It is only important to note that it only in designing the scaffold, type of fabrication and biomaterial
selection depending on the target organ and its cells that can be affected on final application.
Chemistry, architecture, porosity and rate of degradation should provide a sufficient mechanical
environment and should facilitate cell attachment, proliferation and migration, waste nutrient
exchange, vascularization and tissue ingrowth. Also there should be a proper ratio between
degradation of the scaffold and tissue ingrowth.

There are various types of scaffold fabrication methods. At first, only polymeric scaffolds were used
but gradually composite scaffolds and especially ceramic/polymer scaffolds have been used. The
main important scaffold fabrication methods are: Fibers bonding, solvent casting and particulate
leaching, compression molding, extrusion, freeze-drying, phase emulsion, solid free form fabrication
and electro-spinning. Differences between these methods are temperature, pressure, solvent type,
poro-gen (which is responsible for making pores) and etc. Recently researchers used meso-
structured materials in scaffolds to supply drug and biological agents in situ during degradation of
scaffold and growing new tissue.

Ophthalmologic applications:
Vision impairment/low vision, blindness, refractive error (Myopia and Hyperopia), astigmatism,
presbyopia, cataracts, primary open-angle glaucoma, age-related macular degeneration (AMD)
and diabetic retinopathy are common ophthalmologic diseases. To improve the life of these
patients, many implants have been applied.

Bio-electrodes and biosensors:

Bio-electrodes are sensors used to transmit information into or out of the body. Surface or
transcutaneous electrodes used to monitor or measure electrical events that occur in the body
are considered monitoring or recording electrodes. Typical applications for recording
electrodes include electrocardiography, electroencephalography, and electromyography
information into or out of the body

These bio-electrodes are mainly applied in cardiology and neurology applications. A

biosensor is a sensor that uses biological molecules, tissues, organisms or principles to
measure chemical or biochemical concentrations. Biosensors can be used in many medical
and non-medical applications. Biomedical sensors are sensors that detect medically relevant
parameters; these could range from simple physical parameters like blood pressure or
temperature, to analyses for which biosensors are appropriate (e.g. blood glucose).
Biosensors can work by changes in pH, ions, blood gases (O2, CO2 and etc.), drugs,
hormones, proteins, viruses, bacteria, tumors and etc.

Burn dressing and skin substitutes:

Skin is the largest organ that protects body from microorganisms and external forces,
integrates complex sensory nervous and immune systems, controls fluid loss, and serves
important aesthetic function. Deep skin injuries due to deep cuts, burns or de-gloving injuries
can cause significant physiological derangement, expose the body to a risk of systemic
infection, and become a life threatening problem. So the need of skin substitutes depending
on wound depth is felt. An ideal skin substitute must be inexpensive, long -lasting, a bacterial
barrier, semipermeable to water, elastic, easy to apply, painless to the patient, non-antigenic
and non-toxic and has durable shelf-time. Today a lot of commercial skin substitutes are
applied.

Sutures:
Suture is any strand of material that is used to ligate blood vessels or approximate tissue.
Ligatures are used to achieve haemostasis or to close a structure to prevent leakage. The
suture device is comprised of: the suture strand; the surgical needle; and the packaging
material used to protect the suture and needle during storage. The ideal suture must be
biocompatible, sterile, compliant, adequate knot/ straight strength, secure and stable knot,
strength and mass loss profiles adequate for proposed usage, low friction, adequate needle
attachment strength, a traumatic needle design, non-electrolytic, non-capillary, non-
allergenic, non-carcinogenic, minimally reactive, uniform and predictable performance. Silk,
nylon, polyester, cotton, polypropylene, ultra-high molecular weight polyethylene
(UHMWPE), stainless steel and synthetic absorbable polymers such as poly glicolic acid
(PGA), p-dioxanone (PDO) and etc. are the main materials that are used as sutures yet.

Drug delivery systems (DDS):

Drug delivery systems introduced as formulations or instruments which enable to control the
release rate of a biological agent (especially a drug) in the target site. Drug delivery systems
are an interface between patient and drug. Drugs can be introduced to the organ by different
anatomical routes due to disease and drug type: Digestive system (oral, anal), oral, rectal,
parenteral (subcutaneous, intramuscular, intravenous, arterial), mucous membranes,
respiratory tract by inhalation, subcutaneous or intra-osseous are man anatomical routes.

By increasing the size the dosage in single dose administration, side effects would appear so
in order to reduce these side effects, coatings with varying thickness, are applied. Such
formulations are now known as “sustained release” or “prolonged release” products.
However, the pharmacokinetics of such products depended greatly on the local in vivo patient
environment and as such, vary from patient to patient. These systems are called “zero order”
systems because they release drug during time in a constant rate. These reasons were among
the most important driving forces that led to the birth of the field of “controlled drug
delivery” (CDD) in the mid to late 1960s that became known as “macro-scale devices” that
exhibit constant or zero order drug delivery rates, leading to constant plasma drug
concentrations over long time durations of drug delivery. By the rapid growth of nano scale
materials, injectable targeting drug delivery systems appear.

Dental materials:
Restorative materials have been used as tooth crowns and root replacements. Four groups of
materials which are used in dentistry today are metals, ceramics polymers and composites.
Despite recent advances in material science and dentistry, there still is not a proper material
for restorative dentistry. Characteristics of an ideal restorative material are listed below:

•Be biocompatible

•Bond permanently to tooth structure or bone

•Match the natural appearance of tooth structure and other visible tissues

•Exhibit properties similar to those of tooth enamel, dentin and other tissues

•Be capable of initiating tissue repair or regeneration of missing or damaged tissue

Dental materials can be classified in two categories: preventive materials, restorative

material. Preventive dental materials include pit and fissure sealants, sealing agents that
prevent leakage, materials that are used primarily for the antibacterial effects, liners, bases,
cements and restorative materials that are used primarily because the release fluoride,
chlorohexidine or other therapeutic agents used to prevent or inhibit the progression of tooth
decay. This type of materials used for short-term and long-term applications. Restorative
materials can be classified as direct restorative materials and indirect restorative materials
dependent on whether they are used. Direct fabricated intra-orally and indirect fabricated
extra-orally .

Because of importance of restorative dental materials, explain more about this part. Dental
amalgam has been used traditionally for filling dental cavities. Amalgam is a mixture of
copper, tin, zinc, mercury, silver and other trace metals. Later cement dental restorative
materials were used as restorative materials. To achieve adhesive bonding in the general case
of two rigid solids, such as a tooth enamel surface and an orthodontic bracket, it is necessary
to apply a fluid adhesive between them.

Moreover, the fluid must be of appropriate chemical formulation to initially wet both
surfaces, exhibiting a low contact angle. One or both surfaces may have been subjected to
some form of pre-treatment or conditioning with an etchant or primer that, inter alia, may
have modified surface porosity. In this case, the adhesive fluid may be drawn into the solid
surface layers by capillary action. The presence of a suitable fluid between two solids greatly
enhances the potential for intermolecular force interactions at each solid–fluid boundary.
Dental cements can be classified to:
•Conventional acid-base cements

•Poly-electrolyte cements: Zinc poly carboxylates and glass ionomers

•Resin-modified glass-ionomer cements

•Dual-setting resin-based cements

Conventional acid-base cements:

Dental cements are, traditionally, fast-setting pastes obtained by mixing solid and liquid
components. Most of these materials set by an acid-base reaction, and subsequently
developed resin cements harden by polymerization. They have various compositions. This
material is composed primarily of zinc oxide powder and a 50 % phosphoric acid solution
containing aluminium and zinc. The mixed material sets to a hard, rigid cement by formation
of an amorphous zinc phosphate binder. The bonding arises entirely from penetration into
mechanically produced irregularities on the surface of the prepared tooth and the fabricated
restorative material.

Poly-electrolyte cements: Zinc poly carboxylates and glass ionomers :

Poly (carboxylic acid) cements were developed in 1967 to provide materials with properties
comparable to those of phosphate cements, but with adhesive properties of calcified tissues.
This type of cement is composed of zinc oxide and aqueous poly (acrylic acid) solution. The
metal ion cross-links the polymer structure via carboxyl groups, and other carboxyl group’s
complex to Ca ions in the surface of the tissue. Adequate physical properties, excellent
biocompatibility in the tooth, and adhesion to enamel and dentin are main advantages of these
cements being opaque is the main problem with these cements. The need for a translucent
material led to the development of the glass-ionomer cements (GIC). GICs are also based on
poly (acrylic acid) or its copolymers with maleic acids, but utilize a calcium alumina-silicate
glass powder instead of zinc oxide. GICs set by cross-linking of the poly-acid with calcium
and aluminium ions from the glass, together with formations of a silicate gel structure.

Resin-modified glass-ionomer cements:

Poly-acid molecules contain both ionic carboxylate and polymerizable methacrylate groups.
It is induced to set by both an acid-base reaction and visible light polymerization. Adhesive
bonding but not complete sealing is obtained, because of the imperfect adaptation to the
bonded surfaces under practical conditions.

Dual-setting resin-based cements:

Dual-setting resin-based cements are fluid or paste-like monomer systems based on aromatic
or urethane di-methacrylates. They are normally consisting of two-component materials that
are mixed to induce setting. They may also be light-cured. These set materials are strong,
hard, rigid, insoluble and cross-linked polymers.
Reference:
1. Pdf File (Biomaterials)
2. Pdf File (Chapter 13.2 Applications of Biomaterials)