Biomedical Nanotechnology: Introduction, Applications, Diagnostics and Therapy

Let us make an in-depth study of the biomedical nanotechnology. The below given article will help you to learn about the following things:- 1. Introduction to Biomedical Nanotechnology 2. Scientific and Application-Oriented Research 3. Diagnostics 4. Therapy and 5. Other Applications.

Introduction to Biomedical Nanotechnology:

Nanotechnology and Nano engineering stand to produce significant scientific and techno­logical advances in diverse fields including medicine and physiology. In a broad sense, they can be defined as the science and en­gineering involved in the design, synthesis, characterization, and application of materi­als and devices whose smallest functional organization in at least one dimension is on the nanometer scale, ranging from a few to several hundred nanometers.

A nanometer is one billionth of a meter or three orders of magnitude smaller than a micron, roughly the size scale of a molecule itself (e.g. a DNA molecule is about 2.5 nm long while a sodium atom is about 0.2 nm).

The potential impact of nanotechnology stems directly from the spatial and tempo­ral scales being considered: Materials and devices engineered at the nanometer scale imply controlled manipulation of individual constituent molecules and atoms in how they are arranged to form the bulk macroscopic substrate. This, in turn, means that Nano engineered substrates can be designed to exhibit very specific and controlled bulk chemical and physical properties as a result of the con­trol over their molecular synthesis and as­sembly.

For applications to medicine and physiol­ogy, these materials and devices can be de­signed to interact with cells and tissues at a molecular (i.e., subcellular) level with a high degree of functional specificity, thus allowing a degree of integration between technology and biological systems not previously attain­able. It should be appreciated that nano­technology is not in itself a single emerging scientific discipline but rather a meeting of traditional sciences such as chemistry, phys­ics, materials science, and biology to bring together the required collective expertise needed to develop these novel technologies.

The present review explores the significance of Nano science and latest nanotechnologies for human health (Fig. 11.1). Addressing the associated opportunities the review also suggests how to manage far-reaching develop­ments in these areas.

Scientific and Application-Oriented Research:

Living cells are full of complex and highly functional ‘machines’ at nanometer scale. They are composed of macromolecules, in­cluding proteins. They are involved in practi­cally every process in the cell, such as infor­mation transfer, metabolism and the transport of substances. Nanotechnologies offer new instruments for observing the operation of these machines at the level of individual mol­ecules, even in the living cell.

Using atomic force microscopes, it is possible, for example, to measure the bonding forces between trig­ger substances, such as hormones, and the as­sociated receptor proteins that act as switches in the cell membrane. Biomolecules can be labeled using quantum dots. The intense light of a specific wavelength that these Nano crystals emit enables the path followed by the biomolecules in the cell to be precisely traced. A great deal of this research is concerned with obtaining information on basic biochemical and biophysical processes in healthy and dis­eased cells.

This knowledge can provide the basis for the development of new prevention strategies and therapies. Besides this primarily knowledge-broadening research, research is also underway into numerous possible ap­plications for nanotechnologies in medicine.

Research efforts are particularly intensive in the search for new methods and tools for imaging, sensing, targeted drug and gene deliv­ery systems. More research is also underway into applications in fields such as, tissue med­ical implants and disinfection. Clinical applications are currently scarce partly because of stringent safety requirements. Nevertheless, experts expect a great deal from Nano medicine especially in the longer term (Fig. 11.2).

Diagnostics:

The enormous increase in knowledge of the human genome (genomics) and of expres­sion products, proteins (proteomics), makes it possible in an increasing number of cases to trace diseases to abnormalities at the molecu­lar level. In theory, this gives rise to the pos­sibility of making a diagnosis at a very early stage—and of possibly starting treatment— even before the initial symptoms of the dis­ease appear. Attention in medicine is therefore increasingly focusing on prevention.

Neona­tal screening (by means of a heel prick) for metabolic diseases is a good example of this. The medical profession has an ever increas­ing number of technical tools at its disposal for detecting these molecular bio marks. It is in this field that the impact of nanotechnology will probably be noticed first (by 2015). The diagnostic research can be conducted in the laboratory using samples taken from the human body (in vitro research) but it can also be carried out directly on the patient (in vivo). This distinction is important because, in the latter case, the tools/agents have to meet more stringent requirements.

In the Laboratory:

Research into patients’ genetic material (DNA) can be conducted to measure gene expression—the degree of RNA production in diseased tissue, or to ascertain which variant of a particular gene a person has. Many hu­man genes exist in several forms, which only differ in a single base pair. These are known as single nucleotide polymorphisms (SNPs).

The corresponding protein variants may dif­fer from each other in a single amino acid and then display a considerable difference in functionality. SNPs are the root of all kinds of genetic disorders but also affect a person’s sensitivity to chemical substances, includ­ing medicines. This refers to their therapeu­tic effect as well as their side-effects.

Genetic research offers major possibilities for iden­tifying gene types that predispose a person to certain diseases and for achieving better matches between individual patients and the medicines they are prescribed.

DNA chips used for analysing DNA have been available for a few years now. They are currently widely used in scientific, biomedi­cal research but they are rarely used in clini­cal practice. The chips comprise an inert sup­port which carries micro-arrays of hundreds to thousands of single-strand DNA molecules with different base sequences.

DNA from a tissue sample that has been labeled with a radioactive or fluorescent material can be identified on the basis of the place on the chip where it binds to the chip DNA. The Dutch Cancer Institute has been using a DNA chip since 2003 to predict the spread of breast tumors on the basis of gene expression pro­files.

This information makes it much easier than it was in the past to determine which patients would benefit from supplementary chemotherapy after the tumor has been sur­gically removed. Similar chips are being de­veloped for the diagnosis of leukemia’s and mouth and throat tumors. DNA chips and other biochips were originally an achieve­ment of micro technology but miniaturization is advancing here too, as with computer chips. Nanotechnologies are also increasingly playing a role in producing the chips and in increasing their detection sensitivity and reli­ability.

A new Nano technological analytical method uses quantum dots. DNA in a sample is identified on the basis of its bonding to DNA mol­ecules of a known composition embedded in micro-meter-sized polymer spheres contain­ing various mixtures of quantum dots, each of which provides a unique spectral bar code (colour code).

American researchers have used this-method to study SNPs in genes that code for enzymes of the cytochrome P450 family which are involved in the breakdown of substances (including medicines) in the body. The method is very suitable for study­ing large quantities of samples on many SNPs simultaneously (multiplex analyses).

In theory, the composition of DNA mole­cules can also be ascertained by pulling them through Nano-pores in a membrane by means of an electric potential difference. The base sequence can be deduced from the time pro­file of the electric current through the pores.

Researchers have now used this method to identify a mutation in a HIV gene that makes the virus resistant to a particular medicine. If this method, which is still being developed, can be perfected, it will result in a much fast­er way of determining the base sequence of DNA than has thus far been available. This would involve having to place hundreds of pores on a chip.

The aforementioned techniques would, in principle, also be suitable for identifying oth­er biopolymers, such as proteins and carbo­hydrates. Nevertheless, American research­ers have succeeded in developing a chip to detect prostate cancer. The chip contains around one hundred cantilever sensors (mi­cro-meter-sized, nanometers thick miniscule levers), which are coated on one side with an­tibodies to prostate-specific antigen (PSA), a biomarker for that disease.

Bonding of PSA from a sample placed on the chip bends the cantilevers several nanometers, which can be detected optically. This enables clinically relevant concentrations of PSA to be mea­sured. Antibodies placed on nanowires can be used in a similar way to detect viruses—in a blood sample for example. The bonding of a single virus particle to an antibody results in a change in the nanowires electric con­ductance.

The method is extremely sensitive, which means that an infection can be detect­ed at a very early stage. It is also suitable for multiplex analyses. Work is also underway on sensors based on carbon nanotubes, for use in micro-arrays. Detection methods based on cantilevers, nanowires or nanotubes offer the added advantage that it is not necessary to la­bel the sample.

Labs-on-a-chip are pocket-sized laborato­ries. They can be used for analysing biopo­lymers but also for research and for manip­ulating cells. They are expected to play an important role in the further development of biosensors for the detection of pathogen­ic bacteria. In due course there will also be possibilities for point-of-care applications, in which simple analyses can be made in the general practitioner’s surgery or in the pa­tients’ homes and carried out by the patients themselves.

Researchers of the University of Trinity are currently working on the develop­ment of a lab-on-a-chip for measuring lith­ium concentrations in the blood. A chip of this kind would enable patients who use psycho-pharmaceuticals based on lithium to keep the lithium concentration in their blood at the right level. The ease of use would be compa­rable with that of current devices that enable diabetic patients to measure glucose levels in their blood. Photonic explorers for bio-analysis with biologically localized embedding (PEBBLEs) are a final example.

These sensors are a few hundreds of nanometers in size and are composed of an inert capsule, made of polymers for example, containing an indica­tor colouring agent that emits light as soon as a substance being analysed diffuses through the capsule to the inside and binds with the colouring agent.

PEBBLEs were developed for measuring concentrations of small ions and molecules—such as ions of hydrogen, calcium, magnesium and zinc, or glucose—in living cells. Once the Nano capsules have been introduced into a cell, their light emis­sion (and cessation of emission) can be moni­tored using a microscope. Tools of this kind are useful when studying certain diseases. For example, an abnormal zinc balance is a characteristic of brain disorders such as Al­zheimer’s disease and Parkinson’s disease.

In Vivo Diagnostics and Imaging:

In the case of in vivo diagnostics, patients are given contrast agents or radiopharmaceuti­cals. Their specific properties mean that these agents are useful in imaging pathophysi­ological changes and functional changes such as changes in blood flow in cells, tissue and organs. The term molecular imaging is often used, as todays imaging techniques are in­creasingly concerned with making molecular biomarkers of disease processes visible, for instance a receptor protein on the surface of a cancer cell.

To this end, besides being given a contrast agent (the imaging component), a carrier molecule or particle is also given a molecule that specifically binds to the bio- marker, such as an antibody (the targeting component). Various techniques have been developed, each with its own contrast agents and imaging equipment: methods based on ultrasonic vibrations, radioactive substances (including positron emission tomography, PET), magnetic resonance imaging (MRI) and fluorescent substances. Each has its own possibilities for applications and its own re­strictions.

Imaging that focuses on molecular biomarkers makes early detection of diseases possible and provides information on appro­priate therapies. Imaging is also very suitable for monitoring, evaluating and optimizing treatment that is being provided. Nanotech­nologies offer numerous possibilities for im­proving existing and designing new imaging techniques.

Nanoparticles of perfluorohydrocarbons combined with a lipid layer have multiple uses. They are suitable as an ultrasonic con­trast agent. If gadolinium compounds or radioactive substances such as technetium- 99 are combined with the lipid layer of the nanoparticles, they are also suitable for MRI, or scintigraphic imaging.

Given the right targeting molecule, the particles can make pathogenic changes in blood vessels visible. The nanoparticles are currently being studied for use as a contrast agent for the diagnosis of atherosclerosis, thrombosis and (tumor) angiogenesis. A clinical study is expected to start by 2015. Super paramagnetic nanoparticles of iron oxide are-now being used clinically as an MRI contrast agent. They accumulate after intra­venous administration in the liver, the spleen and the lymph glands, thereby enabling stud­ies of those organs.

Patient-based research has indicated that they can also increase detectability of tumor metastases in lymph glands. Combined with dendrimers (Fig. 11.3), the particles can be used for marking living cells. Magneto dendrimers of this kind make it possible to, for example, monitor the migration and division of transplanted cells in the body.

The method, which has already been used successfully on laboratory animals, may prove to be of valuable assistance in the future in stem cell therapy. Gadolinium den­drimers are also being developed for use as contrast agents. The first of these agents are almost ready for introduction on the mar­ket. Depending on their size and solubility in water or fat, they are suitable for examining blood vessels, kidneys, liver or lymph glands.

Optical imaging techniques use fluorescent colouring agents which are taken orally or injected and then accumulate in a tumour, for example. The tumour cells fluoresce when irradiated with laser light. Because the laser light cannot penetrate deep into the body, this technique can only be used for imaging tumours in or just below the skin or in tissue that is accessible using an endoscope.

Intensive research has been underway for several years now into new optical methods based on the use of nanoparticles. Quantum dots are at the most advanced stage (Fig. 11.4) of development. These Nano crystals have the advantage over colouring agents that they fade less quickly over time and do not react with cell components.

Moreover, quantum dots of different colours can be made to fluo­resce with laser light of the same wavelength, which makes multiplex applications possible. Nanoparticles have already been successfully used in cell cultures and laboratory animals to colour biomarkers on the surface of can­cer cells, to monitor the development of cell lines in a frog embryo, to make blood vessels visible in mice and lymph glands in pigs.

The hope is that the latter application will in due course improve the possibilities for tracing tumour metastases. All these applications are based on the fact that Nano-materials because of their minute size can easily enter even the smallest compartment of the cell.

The quantum dots are provided with a layer of lipids or polymers, to prevent heavy metals from being released. However, before clinical applications can be considered, research will have to show that coatings of this sort are also effective in the long term.

Contrast agents can sometimes also act as a medicine. For example, under the influence of laser light of a certain wavelength and in the presence of oxygen, some fluorescent colouring agents produce toxic substances which can destroy tumour cells by oxidation.

In addition, it is theoretically possible to combine diagnosis and therapy by providing nanoparticles not only with targeting molecules and contrast agents but also active substances. The Nano-particle then also acts as a drug delivery sys­tem.

Therapy:

Drug Delivery:

Many substances that could, in theory, be used as medicines have the disadvantage that they are hardly, if at all, able to reach the dis­eased organs or tissues in the body.

There are various possible reasons for this:

1. The substance is hardly, if at all, soluble in water

2. The substance is broken down in the body or inactivated before it reaches its target

3. The substance is hardly, if at all, capable of passing certain biological barriers (cell membranes, placenta, and blood brain bar­rier)

4. The substance distributes non-specifically to all kinds of tissues and organs.

Substances of this kind are, therefore, inef­fective or lead to undesirable adverse side- effects. The German microbiologist Paul Ehrlich conceived (in early 1900s) of the idea of using ‘magic bullets’ to direct medicines at their target more effectively. This idea was taken up again at the end of the 1960s and researchers have since been developing such drug delivery systems. Their miniscule di­mensions mean that all kinds of nanoparticles are suitable for use in systems of this kind.

Depending on the type of particle, the active substance can be encapsulated or attached to the surface. This means that even if they dis­solve poorly in water, they can be transported in an aqueous solution, such as blood and are better protected against degradation by enzymes, for example. A suitable coating on the nanoparticle can prevent identification and removal by the immune system.

Selective accumulation in the target organ or tissue can arise through various mechanisms. The first mechanism is passive. An example of this would be to use the high permeability of the walls of blood vessels and the reduced lymph drainage in tumor tissue. However, it is also possible to provide nanoparticles with ‘targeting molecules’ (e.g. specific antibodies or folic acid), which ensure that the delivery system primarily bonds to the diseased tissue (Fig. 11.5). However, this can aid detection by the immune system.

When provided with suitable targeting molecules, some nanoparti­cles are able to transport medicines across the blood-brain barrier to treat brain tumors, for example. The cells being treated can then take up the delivery system containing the ac­tive substance by means of endocytosis. Combining the delivery systems with con­trast agents, fluorescent or radioactive sub­stances also makes it possible to use imaging techniques to monitor how successful the se­lective transport to the destination has been.

Once it has reached the target area, the active substance has to be released from the carrier at the correct rate. This can occur spontane­ously by gradual diffusion, in combination with the delivery system’s degradation or oth­erwise.

It may also occur as a result of special conditions at the destination, such as a dif­ferent acidity level, salt concentration, tem­perature or the presence of certain enzymes. The accumulation of the delivery system and/ or the release of the active substance at the right place can also be controlled from out­side by influencing conditions in the target organ or tissue by means of magnetic fields, near-infrared radiation, ultrasonic vibrations or heat. The delivery system used and the ex­ternal treatment have to be precisely matched to each other for this purpose.

The requirements that delivery systems have to fulfil are:

1. Their residence time in the blood must be long enough to enable accumulation in the target tissue

2. They must be capable of containing suf­ficient active substance

3. The systems or their degradation products must have a favourable toxicity profile

4. They must have a shelf life that is long enough to allow storage and distribution

5. The effectiveness must be in proportion to the costs.

Research into the suitability of a large va­riety of nanoparticles for use as a delivery system is currently underway. Which parti­cles are most suitable depends on the active substance that has to be transported, the tar­get organ and the method of administration (oral, inhalation, dermal, by injection). Some particles, such as nanoparticles of polymer or of solid fat, appear to be usable for transport­ing a wide range of substances.

The scope for using other, especially inorganic, nanopar­ticles is smaller. Most delivery systems are currently being developed for transporting anti-tumour agents, genetic material (gene therapy) and proteins and peptides. Nano­particles of polymers as delivery systems for active substances have been taking place since the mid-1970s.

The usefulness of other sys­tems, such as nanoparticles of solid fat, dendrimers, fullerenes and Nano crystals of the active substance, only began to be studied in the early or mid-1990s. There are now various medicines with delivery systems on the mar­ket and many are in the clinical study phase.

The future for drug delivery systems is expect­ed to be bright, even if significant obstacles still have to be overcome. Obstacles include the development of methods to increase the specificity of delivery systems for target cells, to more precisely regulate the bio-availability of active substances in the target tissue and to get active substances to the destination within the cell more efficiently.

Nanoparticles as Medicines:

Besides acting as a delivery system, in some cases nanoparticles can act as an active sub­stance. Once they have found their way through the bloodstream into a tumour, or have been injected directly into it, metal- containing nanoparticles can be heated using near-infrared radiation or a rapidly oscillat­ing magnetic field so that the tumour cells die. As yet, this relates to research conducted using laboratory animals. It may also be pos­sible to use single-wall carbon nanotubes in a similar way.

In vitro studies have in fact shown that, if combined with folic acid as targeting molecules, the tubes are selectively taken up by cancer cells. These cells can then be killed by using near-infrared radiation to heat the tubes (Fig 11.5). Healthy cells appeared to take up few, if any, nanotubes and not to be affected by the near infrared radiation.

Recent in vitro and in vivo studies have revealed that some nanomaterial’s are en­dowed with innate anti-platelet properties thus indicating their potential as future anti­thrombotic drugs. Further studies are already underway to characterize the fibrinolytic behaviour of these nanomaterial’s in various pathological conditions like diabetes, stroke, and myocardial infarction [Shrivastava S. et al, unpublished data].

Passive Implants and Tissue Engineering:

Artificial joints, such as artificial hips, nor­mally have a life of around ten to fifteen years, after which complications occur, such as wear or implant loosening, and further operations are required. Nanotechnologies could help re­duce these problems. The implants, which are usually made of titanium or alloys of cobalt and chromium, can be provided with a thin layer of a Nano crystalline structure, which is harder and smoother and consequently more resistant to wear.

This would also result in less wear of the artificial socket, which is generally made of a special type of polyethylene. More­over, the layer would ensure that the body better tolerates the implant (better biocompatibility). The suitability of various materials for use as a coating is currently being studied: diamond, metal-ceramic and hydroxyapatite. The latter material is a natural component of bone, 70% of which consists of the mineral hydroxyapatite, with the remaining 30% con­sisting of organic fibers (collagen).

Hydroxy­apatite has been used as a coating in implants for some time but new production methods now make it possible to apply layers with a grain size in the nanometer, rather than the micro-meter scale. This makes their structure more like that of natural hydroxyapatite in bone, which likewise has a Nano crystalline structure (grain size less than 50 nm). This aids biocompatibility.

The layer can even en­courage the growth and bonding of the sur­rounding bony tissue. In vitro research has shown that bone-forming cells (osteoblasts) adhere better and deposit more calcium on materials with a grain size in the nanometer range than on conventional materials with a grain size in the micro-meter range. This is presumably related to the higher absorption of proteins that stimulate cell adhesion.

Bone re-sorbent cells (osteoclasts) also function better on these nanomaterial’s. Proper, coor­dinated function of both types of cells in es­sential for the formation and maintenance of healthy bony tissue and, therefore, for strong bonding between the implant and the sur­rounding bone.

This is extremely important for implants that are attached without the use of bone cement. Implants provided with a hy­droxyapatite layer with a nanostructure are currently being tested in patients, in 2000; a patient in the Maastricht University Hospital was the first to receive an artificial hip with such a coating.

Nanoparticles of hydroxyapa­tite can also be introduced directly into dam­aged bones to accelerate the repair of bony tissue. In recent years, a few medicines have been admitted that work according to this principle. Implant coatings with a nanostruc­ture based on diamond and metal-ceramic are still at the research stage. Their main ben­efits are hardness, smoothness, corrosion re­sistance and good bonding to the implant.

The mechanical properties and biocompat­ibility of implants can also be improved by providing the material that is used to make the implants with a nanostructure. This is possible by applying a thin layer of titanium dioxide with Nano pores. An added advantage of this approach is that the layer can be made in a way that metal ions with an antiseptic ef­fect such as copper ions are slowly released.

This reduces the likelihood of bacterial infec­tions, which are a frequent complication with implants. Another possibility is to make the implants from Nano powders of titanium di­oxide or aluminium oxide using a sinter pro­cess. Promising alternative materials include organic polymers with a nanostructure and composite materials of organic polymers into which Nano fibers of carbon or nanoparticles of titanium, aluminium or hydroxyapatite have been mixed.

The advantage of the or­ganic polymers is that they dissolve gradu­ally while new bony tissue is being formed. Studies are also underway of the possibilities of generating bone with the help of scaffolds of carbon nanotubes. The orthopedic applications are closest to being used on patients, but biodegradable scaffolds of Nano fibers consisting of natural or synthetic organic polymers are already used to cultivate other tissues, such as carti­lage, muscle tissue, nerve tissue and vascular tissue in vitro.

Here too, the goal of the Nano-structure is to imitate the natural extracel­lular matrix. Researchers recently succeeded in using Nano fibers to regenerate brain tis­sue in vivo. Young and adult hamsters that had been blinded as a result of intentionally caused brain damage had their sight restored within a few weeks of scaffold-forming Nano-material being injected into the brain. It may also be possible to use the method in the fu­ture to repair damaged human nerve tissue.

Stents are a completely different type of im­plant. They are small tubes of woven thread used to dilate blood vessels. Inflammatory reactions often occur and lead to the blood vessel closing again. This problem is dealt with using stents with a coating of aluminium oxide which is provided with Nano pores. A radioactive substance can be applied to them, which prevents the stent from clogging.

The pores ensure that sufficient radioactive ma­terial can be introduced and that it is released very gradually. The functionality and safety of these stents still has to be confirmed in ani­mal trials. Research is also underway into the possibility of using the lotus effect: a coating of titanium compounds is used to prevent clotting reactions owing to conformation changes in proteins in the blood caused by their contact with the stent wall.

Active Implants:

Active implants are implants that contain a source of energy. They can be divided into two groups on the basis of their function. The first category comprises implants for administering medicines, such as insulin pumps and morphine pumps. They have been in use for a long time. Work has also been underway for several years on implantable microchips for the storage and controlled release of ac­tive substances. The benefits of this approach to administering medicines include the fact that the medicines go directly to the location where they are needed and can, if required, be administered at varying rates.

The release could also be controlled by a biosensor that responds to physiological parameters. The first system of this kind is soon due to be test­ed on patients. The second group comprises neural pros­theses, which are intended to repair or take over nerve functions. For instance, they bridge damaged nerve paths, provide impuls­es for muscles or replace senses.

This catego­ry includes cochlear implants (for restoring hearing), pacemakers and defibrillators (for regulating the heart beat), bladder stimula­tors (for controlled emptying of the urinary bladder by spinal cord lesion patients), deep- brain stimulators (to combat tremor in pa­tients with Parkinson’s disease), peroneus stimulators (to combat drop foot).

These are all currently used in patients and some have been in use for decades. On the other hand, retinal implants to restore the sight in patients with a damaged retina are still in development. In recent years, a great deal of research has been conducted into this in the United States, Germany and Japan. Although considerable advances are being made and the first clinical tests are already underway, some major obstacles still have to be overcome.

It will probably be years before ‘artificial retinas’ are as common as the other neural implants. For some years now, vari­ous research groups in the United States have also been working on Neuroprostheses that enable devices to be operated by thought. To this end, one or more chips with electrodes are fitted to the motor cerebral cortex, which register the electrical signals associated with thoughts.

These prostheses are also referred to as brain-machine interfaces. They have now succeeded in enabling rats to operate handles by ‘brain power’ and monkeys to operate the cursor of a computer or a robot arm. A few years ago, an ALS (Amyotrophic lateral scle­rosis) patient had an electrode implanted in the cerebral cortex, to enable him to operate a computer.

In 2004, a Neuroprosthesis was fitted to a paralyzed man. It enables him to operate the cursor of a computer by thought, play video games, and operate a light switch and to select a television channel. The findings were presented at the annual meeting of the American Academy of Physical Medicine and Rehabilitation, in Phoenix, in October 2004.

The ultimate goal, which is still far-off, is to enable patients to operate arm or leg pros­theses or even to restore their control of their paralyzed limbs. Conversely, it also possible to control rats remotely by administering electrical stimuli in the parts of the brain involved in touch and in experiencing pleasant feelings.

These so called ‘robot-rats’ could be used to search for victims underneath the rubble of collapsed houses, to detect landmines or be used as mobile biosensors. All these active implants are essentially products of micro technologies but nanotechnologies may play an impor­tant role in their improvement and further development.

Research is mainly concerned with increasing functionality, fixation in the surrounding tissue and biocompatibility by modify the surface at the Nano scale. For example, electrodes with a Nano porous sur­face are being developed for retinal implants. This nanostructure increases the electrodes’ surface area by a factor of one hundred, which is necessary for proper signal transfer from the electrodes to the tissue.

The micro- electrodes of Neuroprostheses that register electrical signals in the brain often only work for a few weeks. They do not usually become defective but the surrounding tissue gets damaged and non-conductive scar glial-cell tissue grows. In vitro research has shown that a Nano porous surface structure reduces glial- cell adhesion and promotes the formation of outgrowths of nerve cells. A possible expla­nation for the stimulating effect on the nerve cells is that they are naturally embedded in an extracellular matrix with a nanostructure of microtubuli and laminin.

To combat rejec­tion reactions or infections, coatings can be applied that release medicines gradually. An antiseptic layer based on silver nanoparticles is already being used in Germany on cochlear implants. Other examples of contributions made by nanotechnologies to active implants include the membranes with Nano pores in microchips for drug delivery and batteries with a higher energy-storage capacity.

Other Applications:

Disinfection:

The disinfectant effect of silver has long been known but the use of silver in combating pathogenic microorganisms decreased with the emergence of organic antibiotics. The increasing resistance of bacteria to antibiotics has resulted in renewed interest in silver as a disinfectant. The antiseptic effect is based on silver ions. They block the enzymes required for oxygen metabolism, destabilize the cell membrane and block cell division. Bacte­ria are not expected to develop resistance to silver, owing to the diversity of the working mechanisms.

Especially in the form of nano­particles, silver is extremely effective thanks to the large contact area with the environment. Moreover, the particles have the advantage that they can be readily integrated with other materials like (Fig. 11.6) globular or fibrous proteins [communicated data] and polymers. The nanoparticles then act as depots that continually release new silver ions.

When ap­plied to medical instruments or implants, an­timicrobial layers of this kind can help reduce the number of infections. Current research is studying uses on catheters, cochlear implants and in bone cement. Anti-microbial wound dressing containing Nano crystalline silver are already on the market.

Titanium dioxide nanoparticles also have a bactericidal effect. This is based on a photo- catalytic effect. Under the influence of ultra­violet radiation and in the presence of water and oxygen, the particles form extremely re­active molecules (radicals), such as hydroxyl and per-hydroxyl radicals, which kill micro­organisms. Titanium dioxide can be used to produce antiseptic surfaces that only work in the presence of UV radiation. Fullerenes also have an antimicrobial effect in the presence of light. Various antimicrobial products based on nanoparticles are already on the market.

Identification, Security and Logistics:

Radio frequency identification labels (RFID labels) consist of a microchip to which a ra­dio antenna is attached. The chip can contain information on a product that contains it or to which it is attached. A scanning device can activate the chip by means of the antenna, which, in turn, transmits the information stored in the chip. The labels are used for identification and security purposes and for following flows of goods. They have been in use for some time, for locating stolen cars bicycles, for example, and for identifying do­mestic pets and cattle.

The labels are a product of micro technology but nanotechnologies of­fer possibilities for making them smaller and cheaper. This is expected to increase their use considerably. RFID labels are already used in hospitals and care institutions. They are used to prevent newborns from being abducted or confused or demented patients from wander­ing away unnoticed.

They are also increasingly being used for identifying patients or samples taken from patients, alongside or instead of labels with bar codes. This is to enable an early response when the wrong patient is taken to an operating room, for example. They are also expected to reduce the number of wrong blood transfusions. The labels can also simplify the tracing and localization of expensive hospital equipment, make it easier to trace medicines and to help in combating drug counterfeiting. Implanting RFID labels in victims of disasters can facilitate their sub­sequent identification.

Meanwhile, RFID labels the sizes of a grain of rice are available for implantation under the skin. The Food and Drug Administration in the United States approved a label of this kind in 2004. A person’s medical records can be stored on the chip. The idea behind this is that faster availability of the right medi­cal information could save a person’s life in an emergency. Apart from health care these kinds of chips are also finding important role in agriculture and food technologies.

Hence, the multidisciplinary field of nano­technology s application for discovering new molecules and manipulating those available naturally could be dazzling in its potential to improve health care. The spin-offs of Nano-biotechnology could be utilized across all the countries of the world. In the future, we could imagine a world where medical Nano devices are routinely im­planted or even injected into the bloodstream to monitor health and to automatically par­ticipate in the repair of systems that deviate from the normal pattern.

The continued ad­vancement in the field of biomedical nano­technology is the establishment and collabo­ration of research groups in complementary fields. Such collaborations have to be main­tained not only on specialty field level, but internationally as well. The successful devel­opment and implementation of international collaborations fosters a global perspective on research and brings together the benefits to mankind in general. However, nanotechnolo­gy in medicine faces enormous technical hur­dles in those long delays and numerous failures are inevitable.

Likewise, we should be aware and take precautions against the dangers and negative consequences of Nano biotechnology when applied in warfare—in the hands of ter­rorists, and also disasters associated with its application in energy generation when and wherever it strikes or the risks associated with nanoparticles in blood circulation.

It should be appreciated that nanotechnology is not in itself a single emerging scientific disci­pline but rather a meeting point of traditional sciences—like chemistry, physics, biology and materials science—to bring together the required collective knowledge and expertise required for the development of these novel technologies.