Chapter 4

Molecules in Biomaterials and Tissue Molecules in Biomaterials and Tissue EngineeringEngineering

BiomaterialsBiomaterials ApplicationsApplications

CeramicsCeramics

Aluminum oxideAluminum oxide

CarbonCarbon

HydroxyapatiteHydroxyapatite

Dental and orthopedicDental and orthopedic

CompositesComposites Carbon-carbon fibersCarbon-carbon fibers and matricesand matrices

Heart valves and joint implantsHeart valves and joint implants

Metals - AtomsMetals - Atoms Aluminum, Chrome, Cobalt, Gold,Aluminum, Chrome, Cobalt, Gold, Iridium, Iron, Manganese, Molybdenum,Iridium, Iron, Manganese, Molybdenum, Nickel, Niobium, Palladium, Platinum,Nickel, Niobium, Palladium, Platinum, Tantalum, Titanium, Tungsten,Tantalum, Titanium, Tungsten, Vanadium, ZirconiumVanadium, ZirconiumMetallic alloysMetallic alloys wide variety using metallic atomswide variety using metallic atoms

Joint replacement components,Joint replacement components,

fracture fixation, dental implants,fracture fixation, dental implants,

pacemakers, suture wires,pacemakers, suture wires,

implantable electrodesimplantable electrodes

PolymersPolymers

NylonNylon

Synthetic rubberSynthetic rubber

Crystalline polymersCrystalline polymers

Replacement of soft tissues: skin, Replacement of soft tissues: skin,

blood vessels, cartilage, ocular lens,blood vessels, cartilage, ocular lens,

suturessutures

OrthopedicOrthopedic

Table 4.1 Classification of biomaterials in terms of their base structure and some of their most common applications.

Figure 4.1 These titanium-alloy joint replacements are an example of the many applications for metal biomaterials for implantations. (from http://www.spirebiomedical.com)

Figure 4.2 Polymers are made up of many monomers. This is the monomer for poly(ethylene), a common biomaterial used for medical tubing and many other applications.

Biomedical polymerBiomedical polymer ApplicationApplication

Poly(ethylene) (PE)Poly(ethylene) (PE)

Low density (LDPE)Low density (LDPE)

High density (HDPE)High density (HDPE)

Ultra high molecular weightUltra high molecular weight

(UHMWPE) (UHMWPE)

Bags, tubingBags, tubing

Nonwoven fabric, catheterNonwoven fabric, catheter

  

Orthopedic and facial implants Orthopedic and facial implants

Poly(methyl methacrylate) (PMMA) Poly(methyl methacrylate) (PMMA) Intraocular lens, dentures, bone cementIntraocular lens, dentures, bone cement

Poly(vinyl chloride) (PVC) Poly(vinyl chloride) (PVC) Blood bags, catheters, cannulae Blood bags, catheters, cannulae

Poly(ethylene terephthalate) (PET)Poly(ethylene terephthalate) (PET) Artificial vascular graft, sutures,Artificial vascular graft, sutures,

heart valves heart valves

Poly(esters)Poly(esters) Bioresorbable sutures, surgicalBioresorbable sutures, surgical

products, controlled drug releaseproducts, controlled drug release

Poly(amides) (Nylons)Poly(amides) (Nylons) Catheters, suturesCatheters, sutures

Poly(urethanes) (PU) Poly(urethanes) (PU) Coat implants, film, tubing Coat implants, film, tubing

Table 4.2 The clinical uses of some of the most common biomedical polymers relate to their chemical structure and physical properties.

Figure 4.3 This artificial heart valve is coated with Silizone, a biocompatible material that allows the body to accept the implant. (from http://www.sjm.com/devices/).

Biological systemBiological system Example of applicationExample of application

Blood Blood Hematopoietic (production of red bloodHematopoietic (production of red blood

cells by) stem cells culture cells by) stem cells culture

Cardiovascular Cardiovascular

Endothelialized synthetic vascularEndothelialized synthetic vascular

grafts (angiogenesis)grafts (angiogenesis)

Regeneration of the arterial wallRegeneration of the arterial wall

Compliant vascular prosthesesCompliant vascular prostheses

Liver and pancreas Liver and pancreas Bioartificial pancreatic isletsBioartificial pancreatic islets

Bioartificial liver Bioartificial liver

MusculoskeletalMusculoskeletal Cartilage reconstructionCartilage reconstruction

Bone reconstruction Bone reconstruction

NeuralNeural

Neurotransmitter-secreting cellsNeurotransmitter-secreting cells

(polymer-encapsulated)(polymer-encapsulated)

Neural circuits and biosensorsNeural circuits and biosensors

Peripheral nerve regeneration Peripheral nerve regeneration

SkinSkin Bioartificial skin substitutesBioartificial skin substitutes

Table 4.3 Some examples of current applications in tissue engineering. Not all of the listed applications are at the same developmental stage.

Condenser

Objective

Projector

Sample

Fluorescent screen

Electron source

Figure 4.4 (a) TEM microscope. The electron beam passes through the sample, generating on the fluorescent screen a projected image of the sample, which can be recorded by photographic means.

Condenser

Condenser

Condenser

Sample

Electron source

Deflector

CRT

Detector

Figure 4.4 (b) SEM microscope. Condenser lenses focus the electron beam on the specimen surface leading to secondary electron emission that is captured by the detector and visualized on the CRT screen. Both TEM and SEM operate in a particle free (vacuum) environment.

Incident beam (primary electrons)

Secondary electrons

Backscattered electrons

Figure 4.5 Principle of SEM operation. An incident beam of primary electrons displaces orbital electrons from the sample atoms resulting in secondary electron emission which is detected for image formation. Some primary electrons pass by the nucleus to become backscattered electrons.

Figure 4.6 (a) An STM probe tip made of tungsten magnified 4,000 times. The tip is very small, and can be ruined on a sample, which is seen in Figure 4.6 (b). (from http://www.orc.soton.ac.uk/~wsb/photos.htm).

T he assem bly A s lidesins ide the assem bly B ,

driven by the Z -approach drive p iezo.

A

BS lid ingsurfaces

Z-approachdrive p iezo

Scannerp iezo

Sam pleholder cage

Figure 4.7 This is a sample of a piezotube. There are different approaches, but all use the same method of two opposing piezoelectric materials to move the sample in each axis. (from http://www.topac.com/l).

Display

Piezotube

Tip

I/V converter

Tunnel voltage source

Scanner voltage

Voltage

processor

Scan controller

Sample

Figure 4.8 STM schematics. The tip of a probe scans the surface of the sample. Three dimensional movements of the sample under the tip are accomplished using a voltage-controlled piezoscanner. The tunneling current crossing from the sample to the tip is further processed leading to a topographical image.

Laser

Lens

Sample

Piezoscanner

Two-segment photodetector

Mirror Cantilever

Figure 4.9 Sketch of an SFM. A laser beam is focused on the cantilever, and reflected back to a two-segment photodetector. The difference in output from each segment is proportional to the deflection amplitude of the cantilever scanning the sample.

Photoelectron

(b)

(d)

Auger electron

Fluorescent radiation(c)

(a)X-ray photon

Figure 4.10 When an X-ray photon (a) interacts with an atomic orbital electron of the sample, a photoelectron (b) is emitted. The now unstable atom must relax to the ground state. The relaxation process can be accomplished by either of two mechanisms: (1) an outer orbital electron releases energy as fluorescent radiation (c) while occupying the place of the emitted photoelectron, or (2) the excess energy is used to unbind and emit another outer orbital electron called an Auger electron (d). These mechanisms operate for different sample depths, yielding the Auger electron emission characteristic of the outermost surface of the sample.

Binding energy (eV)0 1000

100

Inte

nsi

ty (

%)

Figure 4.11 A typical XPS spectrum, showing photoelectron intensity as a function of binding energy. Each peak may correspond to a distinct element of the periodic table or to different orbital electrons of the same element. Some peaks may also represent Auger radiation.

Figure 4.12 Basic schematics of an XPS instrument. An X-ray beam strikes the sample surface, giving photoelectron radiation. These electrons enter the hemispherical analyzer where they are spatially dispersed due to the effects of the retarding grid and of the electrostatic field of the concentric hemispheres. Ramping voltages at the retarding grid allow kinetic energy scanning. At the other end of the analyzer electrons are detected, counted, and a spectrum of photoelectron intensity versus binding energy is displayed.

X-ray source

Hemispherical electrostatic analyzer

Slit Display Data

processor Detector

Sample holder

Retarding grid

X -rays

Lenses

Sam ple

Im agingD etector

SpectroscopyD etector

H em ispherica lAnalyser

Irises

ZoomM icroscope

C am era

Figure 4.13 Photograph (from www.thermo.com/eThermo/CDA/Products/Product_Detail/1,1075,15885-158-X-1-1,00.html) and schematics of an ESCALAB. This iXPS instrument offers the capability of parallel imaging, which obtains positional information from dispersion characteristics of the hemispherical analyser and produces photoelecton images with spatial resolution better than 5 m.

Ion generator

Ion detector

Mass analyzer

Processing

Display

Sample

Primary ions

Secondary ions

Figure 4.14 Schematic diagram of a SIMS instrument. Bombardment of primary ions on the sample surface leads to secondary ion emission. A mass analyzer separates these ions in terms of their mass-to-charge ratio. The ion detector converts this ionic current into an electrical signal for further processing. The display presents the SIMS spectra, consisting of the count of ions versus their mass-to-charge ratio.

Infrared detector

Source

Fixed mirror

Sliding mirror Beamsplitter

Figure 4.15 Michelson interferometer. A beamsplitter transmits half of the source radiation to the fixed mirror and the other half to the sliding mirror. A phase difference between the beams can be induced by sliding the mirror causing detection of the two beams at different times. The detector provides the interferogram, a plot of energy as a function of differences in optical paths. Beams have been slightly shifted in the drawing to allow easy following of their path.

c

s

Figure 4.16 When an incident beam traveling at an angle in a medium of refractive index c encounters another medium of refractive index s, it will reflect in a direction given by and refract in the direction given by , verifying Snell’s Law of Refraction.

SV SL

LV

Figure 4.17 Surface tension components of a three-phase system to limit the spread of a drop on top of a surface. is the interfacial free energy for each of the phases. is the contact angle.

NH2 C C OH

H O

R

Figure 4.18 The amino acid molecule. To a central carbon atom, an amino group, a carboxyl group and a hydrogen atom are bonded. R represents the rest of the molecule, which is different for each of the 20 amino acids.

G()

0

1

< > = time average

Figure 4.19 The autocorrelation function G() is 1 when two signals have delay time = 0, then decays to 0 for long delay time.

G() = <I(t) I(t + )>

= delay time

I(t + ) = intensity at (t + )

I(t) = intensity at time t

G() = ACF