17
NANOTECHNOLOGY IN TISSUE ENGINEERING Mr.Nagarajan, V.Amutha  Nanotechnology is an emerging field that c ould potentially make a major impact to human health. Nanoma teria ls promi se to revolu tioni ze medic ine and are increasing ly used in drug delivery or tissue engineering applications. The tissue engineered products that are on the market are all relatively simple. Using Nano technology, more complex  products could be developed. Nanotechnology is being used to alter the surface structure of both tissue engineering scaffolds and implants, primarily to improve cell adhesion.  Nanostructuring can be carried out, for example, by using a scanning probe microscope (SPM) to ‘scratch’ the material surface. The alternative to altering the actual surface structure is creating and structuring particular surface coatings on implants. This can be done to improve their biocompatibility or to improve the interaction between the implant and surrounding tissues. It may be possible to extend the lifetime of an implant, and make it more comfortable for the individual. NANOSTRUCTURING / NANOCOATING : Bi omimic ry , or bi omimet ic s, is the pr ocess of ut il is in g th e wa y nature success full y pr odu ces something to create a ma nmade ma teri al . For exa mple, nanopat terne d polymer scaff olds, mimicki ng the natural way miner als are arran ged, are  being used to make teeth and bone implants.  Nanopatterning involves depositing molecules on a surface. Various techniques can be used - e.g. nanolithography where a beam can be used to deposit ions, or  microcontact printing, where ‘ink’ is transferred onto a surface using a mould – to alter the sca ff old sur fac e . Nano pat ter ning can als o be use d to pla ce cel ls in par tic ula r locations on the scaffold. In doing so, this could create channels to help nutrient exchange within the new tissue. One of the main properties required of a scaffold is a large surface area. . By altering the scaffold surface on a nanoscale level (i.e. by making nanoscale grooves), the surface area can be vastly increased. Cell adhesion is then increased, leading to a greater amount of growth. Similarly, cell attachment is important in order to create a better bond

NANO TECHNOLOGY IN TISSUE ENGINEERING

Embed Size (px)

Citation preview

Page 1: NANO TECHNOLOGY IN TISSUE ENGINEERING

8/7/2019 NANO TECHNOLOGY IN TISSUE ENGINEERING

http://slidepdf.com/reader/full/nano-technology-in-tissue-engineering 1/17

NANOTECHNOLOGY IN TISSUE ENGINEERING

Mr.Nagarajan, V.Amutha

 Nanotechnology is an emerging field that could potentially make a major impact

to human health. Nanomaterials promise to revolutionize medicine and are increasingly

used in drug delivery or tissue engineering applications. The tissue engineered products

that are on the market are all relatively simple. Using Nano technology, more complex

 products could be developed. Nanotechnology is being used to alter the surface structure

of both tissue engineering scaffolds and implants, primarily to improve cell adhesion.

 Nanostructuring can be carried out, for example, by using a scanning probe microscope

(SPM) to ‘scratch’ the material surface. The alternative to altering the actual surface

structure is creating and structuring particular surface coatings on implants. This can be

done to improve their biocompatibility or to improve the interaction between the implant

and surrounding tissues. It may be possible to extend the lifetime of an implant, and make

it more comfortable for the individual.

NANOSTRUCTURING / NANOCOATING :

Biomimicry, or biomimetics, is the process of utilising the way nature

successfully produces something to create a manmade material. For example,

nanopatterned polymer scaffolds, mimicking the natural way minerals are arranged, are

 being used to make teeth and bone implants.

 Nanopatterning involves depositing molecules on a surface. Various techniques

can be used - e.g. nanolithography where a beam can be used to deposit ions, or 

microcontact printing, where ‘ink’ is transferred onto a surface using a mould – to alter 

the scaffold surface . Nanopatterning can also be used to place cells in particular 

locations on the scaffold. In doing so, this could create channels to help nutrient exchangewithin the new tissue.

One of the main properties required of a scaffold is a large surface area. . By

altering the scaffold surface on a nanoscale level (i.e. by making nanoscale grooves), the

surface area can be vastly increased. Cell adhesion is then increased, leading to a greater 

amount of growth. Similarly, cell attachment is important in order to create a better bond

Page 2: NANO TECHNOLOGY IN TISSUE ENGINEERING

8/7/2019 NANO TECHNOLOGY IN TISSUE ENGINEERING

http://slidepdf.com/reader/full/nano-technology-in-tissue-engineering 2/17

 between an implant and the surrounding tissue. The direction of cell growth can also be

affected by nanostructuring, which can aid cell migration. It was shown that

nanostructuring the metal surfaces of implants allows better cell attachment - greater than

90% attachment, compared to approximately 50% on regular surfaces. Typically, metal

implants have relatively smooth surfaces, unlike the natural bone surface, and often the

 body reacts to the implants adversely, impeding their function. The surface of bone tissue

is naturally uneven, with bumps approximately 100nm wide – when this was copied on to

metal surfaces, not only did cell attachment improve, but bone regrowth was also

stimulated. The results so far are from experiments conducted in Petri dishes – the group

are continuing trials.

  Nanotechnology, researchers have developed self-assembling nanotubes as a

nanopatterned coating for titanium implants. DNA chemistry is used to form rosette-

shaped rings, which then combine to form tubes only 3.5 nanometres wide. When

titanium was coated with the nanotubes, similar results were seen as with nanostructuring

the metal surface - cell adhesion was increased by approximately onethird. Further 

research has also shown that by aligning the nanotubes in the same direction, cell

adhesion can again be doubled (compared with non-aligned nanotubes), so that 80% of 

cells are adhered. A team at the Center of Advanced European Studies and Research in

Bonn, Germany, have  used multiwalled carbon nanotubes to create ‘honeycomb-like

matrices’ which could be used as tissue engineering scaffolds. Initial results using mouse

cells to seed the scaffold have been promising, with no cytotoxic side effects seen. The

advantage of using nanotubes over other methods is that signalling molecules or amino

acids sequences can be attached to the nanotubes. By using sequences specific to a

certain tissue type, depending on the implant/scaffold location, cell attachment could be

increased even further. Either using nanotubes alone, or by combining them with typical

scaffold materials could result in improved, more biocompatible scaffolds in the future.

Hydroxyapatite (HA) is used as a scaffold material, but can also be utilized as a thin

coating on metal alloy implants, to mimic natural tissue and promote bonding with the

surrounding tissue Nanostructured HA has been found to give better results than

Page 3: NANO TECHNOLOGY IN TISSUE ENGINEERING

8/7/2019 NANO TECHNOLOGY IN TISSUE ENGINEERING

http://slidepdf.com/reader/full/nano-technology-in-tissue-engineering 3/17

standard HA coatings, and several companies and research groups are now using this

form.

As ceramics, rather than metals, are often used in some implants due to their 

greater resistance to wear, nanocomposite ceramics are being investigated, The material

developed is composed of zirconia nanoparticles and alumina, and has, on a laboratory

scale, been found to give greater resistance to cracking than either material did alone.

Initial results from the project are promising, though various aspects of the production

 process still need refining. The technique could be used to produce ceramic implants that

last more than 30 years. Silicon is another material used for both scaffolds and implants.

UK company pSiMedica has developed BioSilicon, a nanostructured porous silicon.

BioSilicon is both biocompatible and biodegradable, which are particularly desirable

qualities for scaffold materials. Research is being done by pSiMedica into creating forms

of BioSilicon with optimised surface structures for use as a scaffold. BioSilicon could

also be used for implants as it has a high tensile strength, and the company claims that the

degradation product (silicic acid) has a role in encouraging bone growth.

TITANIUM COATING WITH PROTEIN NANOCLUSTERS STRENGTHENS

IMPLANT ATTACHMENT

Researchers have developed an improved coating technique that could strengthen

the connection between titanium joint-replacement implants and a patient’s own bone.

The stronger connection -- created by manipulating signals the body's own cells use to

encourage growth -- could allow the implants to last longer.

Implants coated with "flower bouquet" clusters of an engineered protein that

mimics the body's own cell-adhesion material fibronectin made 50 percent more contact

with the surrounding bone than implants coated with protein pairs or individual strands.

The cluster-coated implants were fixed in place more than twice as securely as plugs

made from bare titanium -- which is how joints are currently attached.

Researchers believe the biologically-inspired material improves bone growth

around the implant and strengthens the attachment and integration of the implant to the

Page 4: NANO TECHNOLOGY IN TISSUE ENGINEERING

8/7/2019 NANO TECHNOLOGY IN TISSUE ENGINEERING

http://slidepdf.com/reader/full/nano-technology-in-tissue-engineering 4/17

  bone. This work also shows for the first time that biomaterials presenting biological

sequences clustered together at the nanoscale enhance cell adhesion signals. These

enhanced signals result in higher levels of bone cell differentiation in human stem cells

and promote better integration of biomaterial implants into bone.

By clustering the engineered fibronectin pieces together, we were able to create

an amplified signal for attracting integrins, receptors that attached to the fibronectin and

directed and enhanced bone formation around the implant.

Total knee and hip replacements typically last about 15 years until the

components wear down or loosen. For many younger patients, this means a second

surgery to replace the first artificial joint. With approximately 40 percent of the 712,000

total hip and knee replacements in the United States in 2004 performed on younger 

 patients 45-64 years old, improving the lifetime of the titanium joints and creating a

 better connection with the bone becomes extremely important.

Researchers coated clinical-grade titanium with a high density of polymer strands -- akin

to the bristles on a toothbrush. And modified the polymer to create three or five self-

assembled tethered clusters of the engineered fibronectin, which contained the arginine-

glycine-aspartic acid (RGD) sequence to which integrins binds.

To evaluate the in vivo performance of the coated titanium in bone healing, the

researchers drilled two-millimeter circular holes into a rat's tibia bone and pressed tiny

clinical-grade titanium cylinders into the holes. The research team tested coatings that

included individual strands, pairs, three-strand clusters and five-strand clusters of the

engineered fibronectin protein.

To investigate the function of these surfaces in promoting bone growth, we

quantified osseointegration, or the growth of bone around the implant and strength of the

attachment of the implant to the bone.

Analysis of the bone-implant interface four weeks later revealed a 50 percent

enhancement in the amount of contact between the bone and implants coated with three-

Page 5: NANO TECHNOLOGY IN TISSUE ENGINEERING

8/7/2019 NANO TECHNOLOGY IN TISSUE ENGINEERING

http://slidepdf.com/reader/full/nano-technology-in-tissue-engineering 5/17

or five-strand tethered clusters compared to implants coated with single strands. The

experiments also revealed a 75 percent increase in the contact of the three- and five-

strand clusters compared to the current clinical standard for replacement-joint implants,

which is uncoated titanium.

The researchers also tested the fixation of the implants by measuring the amount

of force required to pull the implants out of the bone. Implants coated with three- and

five-strand tethered clusters of the engineered fibronectin fragment displayed 250 percent

higher mechanical fixation over the individual strand and pairs coatings and a 400

 percent improvement compared to the unmodified polymer coating. The three- and five-

cluster coatings also exhibited a twofold enhancement in pullout strength compared to

uncoated titanium.

TITANIZED SYNTHETICS

Using nanotechnology, we shall develop synthetic materials with a titanium

coating for implants. While titanium has excellent biocompatibility, and is often used for 

orthopaedic implants, its use was otherwise limited by its rigidity. Titanized synthetics

have a layer of titanium only 30nm thick – making it not only biocompatible, but also

flexible. The titanium and synthetic material are covalently bonded, so are difficult to

separate, and therefore problems such as tearing or the material degrading are not seen,

which would mean less risk of repeat surgeries being required. The first product to be

made of titanized synthetics was a mesh implant for use in hernia surgery, called

TiMESH Use of TiMESH reduces scarring and post-operative pain, in comparison with

regular plastic meshes, due to the biocompatibility of titanium. Between 2002 and early

2004 more than 70,000 European patients received the TiMESH implant . The product

has also been approved for use in Australia, America, and Canada, with the first

American patients receiving the implant at the beginning of 2004. The company has also

developed titanized suture material (TiGOOD), and breast implants with a titanized

silicone shell (TiBREEZE). Both products have been approved for use in Europe. The

technology could potentially be used in conjunction with other metals and synthetic

material.

Page 6: NANO TECHNOLOGY IN TISSUE ENGINEERING

8/7/2019 NANO TECHNOLOGY IN TISSUE ENGINEERING

http://slidepdf.com/reader/full/nano-technology-in-tissue-engineering 6/17

ENGINEERED HUMAN CORNEAS

The ‘Cornea Engineering’ project has brought the aim of reconstructing a human

cornea in vitro. Using nanotechnology, the group aims to use recombinant human ECM

to construct a scaffold for the growth of corneal cell types. The project has several aims,

including developing a hemi-cornea (for use in grafting and an alternative to animal

testing), and a complete cornea. This could potentially overcome the shortage of corneas

available for transplant (due to lack of donors and corrective laser surgery making

corneas unusable), and also the risks of transmitting disease from donor to recipient. It

would also cut the number of animals used in testing the toxicity of chemicals in the eye.

The group plan on using human stem cells from the patient. In order to successfullycreate a complete cornea however, the group have still to find a stem cell that can be used

for the endothelial cells of the cornea.

NANOTECHNOLOGY FOR DRUG DELIVERY

Controlled drug-delivery strategies have made a dramatic impact in medicine. In

general, controlled-release polymer systems deliver drugs in the optimum dosage for long

 periods, thus increasing the efficacy of the drug, maximizing patient compliance and

enhancing the ability to use highly toxic, poorly soluble or relatively unstable drugs.

 Nanoscale materials can be used as drug delivery vehicles to develop highly selective and

effective therapeutic and diagnostic modalities. There are a number of advantages with

nanoparticles in comparison to microparticles. For example, nanoscale particles can

travel through the blood stream without sedimentation or blockage of the icrovasculature.

Small nanoparticles can circulate in the body and penetrate tissues such as tumors. In

addition, nanoparticles can be taken up by the cells through natural means such as

endocytosis. Nanoparticles have already been used to deliver drugs to target sites for 

cancer therapeutics or deliver imaging agents for cancer diagnostics. These vehicles can

 be engineered to recognize biophysical characteristics that are unique to the target cells

and therefore minimize drug loss and toxicity associated with delivery to non-desired

Page 7: NANO TECHNOLOGY IN TISSUE ENGINEERING

8/7/2019 NANO TECHNOLOGY IN TISSUE ENGINEERING

http://slidepdf.com/reader/full/nano-technology-in-tissue-engineering 7/17

tissues. In general, targeted nanoparticles comprise the drug, the encapsulating material

and the surface coating. The encapsulating material could be made from biodegradable

 polymers, dendrimers (treelike acromolecules with branching tendrils that reach out from

a central core) or liposomes (spherical lipid bilayers). Controlled release of drugs (such as

small molecules, DNA, RNA or proteins) from the encapsulating material is achieved by

the release of capsulated drugs through surface or bulk erosion, diffusion, or triggered by

the external environment, such as changes in pH, light, temperature or by the presence of 

analytes such as glucose. Controlled-release biodegradable nanoparticles can be made

from a wide variety of polymers including poly (lactic acid) (PLA), poly (glycolic acid)

(PGA), poly (lactic co-glycolic acid) (PLGA) and polyanhydride. PGA, PLA and their 

co-polymer PLGA are common biocompatible polymers that are used for making

nanoparticles. Since PGA is more susceptible to hydrolysis than PLA, by changing the

ratio of these two components, PLGA polymers can be synthesized with various

degradation rates. Current research into novel nano materials is aimed at improving the

 properties of the materials such as biocompabitility, degradation rate and control over the

size and homogeneity of the resulting nano particles. In order to control the targeted drug

delivery of intravenously delivered nanoparticles, nanoparticle interactions with other 

cells, such as macrophages must be controlled. Various approaches have been developed

to control these interactions, ranging from changing the size of the particle to changing

nanoparticle surface properties.

To remove nonspecific protein adhesion and decrease uptake by macrophages,

nanoparticles can be functionalized using protein replant materials, such as poly (ethylene

glycol) (PEG) and polysaccharides. Nonadhesive surface coatings increase the circulation

time of the nanoparticles and reduce toxic effects associated with non-targeted delivery .

Page 8: NANO TECHNOLOGY IN TISSUE ENGINEERING

8/7/2019 NANO TECHNOLOGY IN TISSUE ENGINEERING

http://slidepdf.com/reader/full/nano-technology-in-tissue-engineering 8/17

More recently, novel approaches aimed at conjugating small molecules

■ Figure 1. Schematic diagram of examples of bottom-up (a) and topdown (b)

nanotechnology approaches for controlled drug delivery: (a) shows an illustration of 

a controlled-release nanoparticle cut in half. The nanoparticle may contain drugs

and will be coated with PEG molecules and targeting molecules to regulate its

interactions with the surroundings inside the body; (b) shows a microfabricated

drugdelivery device containing reservoirs that contain drugs. As the cap for each

reservoir is removed, the drug will be released.

on nanoparticles using high-throughput methods have yielded nanoparticle libraries thatcould be subsequently analyzed for their targeted properties. Also, noncovalent

approaches have been used to surface modify nanoparticles. For example, the layer-by-

layer deposition of ionic polymers have been used to change surface properties of 

nanoparticles, such as quantum dots . Layer-by-layer methods alter the surface charge of 

nanoparticles, which has been shown to regulate nanoparticle biodistribution. For 

example, increasing the charge of cationic pegylated liposomes decreases their 

accumulation in the spleen and blood, while increasing their uptake by the liver and

tumor vessels. To eliminate the need for surface modification schemes, amphiphilic

 polymers may be synthesized by covalently linking biodegradable polymers to PEG prior 

to formation of nanoparticles. For example, nanoparticles can be synthesized from

amphiphilic copolymers composed of lipophilic (i.e., PLGA or PLA) and hydrophilic

(i.e., PEG) polymers. Upon formation of these nanoparticles, PEG migrates to the surface

Page 9: NANO TECHNOLOGY IN TISSUE ENGINEERING

8/7/2019 NANO TECHNOLOGY IN TISSUE ENGINEERING

http://slidepdf.com/reader/full/nano-technology-in-tissue-engineering 9/17

in the presence of an aqueous solution forming pegylated nanoparticles. To target

nanoparticles to the desired tissues, a number of methods have been developed. These

include physical means such as controlling the size, charge and hydrophobicity of the

 particles. In addition, targeting molecules, such as antibodies and peptides, that recognize

specific cell surface proteins and receptors, can be conjugated to the nanoparticle surface

to specifically target specific cell types.

Antibodies and peptides have been successfully used to target nanoparticles to a

number of desired cell types and provide powerful means of directing controlled-release

nanoparticles to specific sites in the body. Potential disadvantages of antibody- and PEG

  peptide-based targeting include their batch-to-batch variation and their potential

immunogenecity. Aptamers, a class of DNA- or RNA-based ligands, may overcome

some of the limitations associated with antibody- and peptide-based drug delivery.

Aptamers have been conjugated to nanoparticles to generate nanoparticles that can target

 prostate cancer cells. Current research in targeting the delivery of nanoparticles involves

validating the in vivo efficacy of the various targeting approaches and developing

methods of enhancing the targeting of the particles without side effects.

Future generations of nanoparticles promise to not only deliver drugs to the

desired sites within the body, but to do so in a temporally regulated manner. For example,

nanoparticles have recently been generated that can be used to sequentially deliver drugs

to cancer cells so that each drug is delivered at the proper time to induce cell death as

well as to prevent angiogenesis. It is envisioned that the development of “smart”

nanoparticles could be a powerful means of further enhancing the functionality of these

nanoparticles. In addition to polymeric nanoparticles, other types of nanomaterials have

also been used for medical applications. For example, quantum dots, nanoparticles with

novel electroluminescent properties and magnetic resonance imaging (MRI) contrast

agents have been used to image cancer cells. Also, carbon nanotubes, nanowires and

nanoshells have also been used for various therapeutic and diagnostic applications. Each

of these materials provides unique physical, chemical and biological properties that are

 based on the nanoscale size and structure of the materials. For example, quantum dots are

more stable than chemical fluorphores, have tighter emission wavelengths and can be

engineered to emit at specific wavelengths by changing its size. Thus, the targeted

Page 10: NANO TECHNOLOGY IN TISSUE ENGINEERING

8/7/2019 NANO TECHNOLOGY IN TISSUE ENGINEERING

http://slidepdf.com/reader/full/nano-technology-in-tissue-engineering 10/17

delivery of these materials could potentially lead to significant medical breakthroughs.

Top-down nanofabrication and micro fabrication approaches based on integrated circuit

  processing may be used to fabricate controlled-release drug delivery devices. Using

 photolithographic and integrated circuit processing methods, silicon-based microchips

have been fabricated that can release single or multiple chemicals on demand using

electrical stimuli.

These engineered micro devices can be used to maintain biological activity of the

drugs and facilitate the local, accurate and controlled release of potentially complex drug-

release profiles. In addition to silicon-based devices, polymeric-based micro fabricated

devices have been made that can release drugs based on the degradation of polymeric

reservoir covers. Micro fabrication techniques have also been used to develop

transdermal drug delivery approaches based on microneedles.

■ Figure 2. Schematic diagram of the top-down (a) and bottom-up

(b)nanotechnology approaches for tissue engineering: (a) Nanofabrication

approaches can be used to generate 3D tissue engineering scaffolds

with controlled pore geometries, shapes and degradation properties;

(b) Nanotechnology can also be used to generate tissue engineering scaffolds from

the self-assembly of nanomaterials, such as amphiphilic peptides that generatehigher order structures such as nanofibers 

These microfabricated needles, which are much smaller than hypodermic needles,

may be used to deliver drugs in a painless and efficient manner. By penetrating through

the outer 10–20 m of skin, microneedles can deliver drugs without activating sensory  

Page 11: NANO TECHNOLOGY IN TISSUE ENGINEERING

8/7/2019 NANO TECHNOLOGY IN TISSUE ENGINEERING

http://slidepdf.com/reader/full/nano-technology-in-tissue-engineering 11/17

nerves of the tissue, thus providing a painless method of delivering drugs. Although the

above examples have been performed using microscale resolution, the current state-of 

the- art in top-down nanofabrication approaches can generate features that are less than

100 nm in resolution. Therefore, the fabrication of nanoscale devices using these

approaches is theoretically possible and may be advantageous for specific drug-delivery

applications in which miniaturized nanoscale devices are desired. Interestingly, bottom-

up and top-down approaches have merged to optimize drug-delivery vehicles. For 

example, microfabricated approaches have been used to develop microfluidic devices that

mimic the body’s vasculature and can be used to test and optimize the interaction of 

targeted nanoparticles with the cells that line the cancer blood vessels. By changing

 parameters such as shear stress and geometry of the channel, as well as nanoparticle

 properties such as size, and surface properties optimized nanoparticle formulations can be

obtained before performing costly animal and clinical experiments.

Tissue engineering combines biology, medicine, engineering and materials

science to develop tissues that restore, maintain or enhance tissue function. To

recapitulate proper function and organization of native tissues in tissue engineering

approaches, it is important to mimic tissue properties at the nanoscale. For example, in a.

 body, the extracellular matrix (ECM) provides a natural web of tissue-specific and

organized nanofibers that support and maintain the cell microenvironment. In addition,

cells in the body reside in a unique environment that is regulated by cell-cell, cell-ECM

and cell-soluble factors presented in a spatially and temporally dependent manner. Thus,

engineering approaches and methods that aim to use tissue engineering principles must

have the same level of complexity. Nanotechnologies and microtechnologies can be

merged with biomaterials to generate scaffolds for tissue engineering that can maintain

and regulate cell behavior. Also, such technologies can be used to regulate in vitro

cellular microenvironment to direct stem cell differentiation.

Many tissue engineering approaches rely on the use of 3D biodegradable

scaffolds that place cells in close proximity to each other. Inside these scaffolds, cells

deposit their own matrix and as the scaffold degrades, they form a 3D tissue structure that

mimics the body’s natural tissues. Nanofabricated and microfabricated tissue engineering

Page 12: NANO TECHNOLOGY IN TISSUE ENGINEERING

8/7/2019 NANO TECHNOLOGY IN TISSUE ENGINEERING

http://slidepdf.com/reader/full/nano-technology-in-tissue-engineering 12/17

scaffolds have the potential to direct cell fate as well as regulate processes such as

angiogenesis and cell migration. Both top-down and bottom-up technologies have been

used to incorporate nanoscale control for tissue engineering scaffolds. Top-down

approaches, such as soft lithography, have greatly enhanced our ability to generate

microscale and nanoscale features since they limit the use of expensive clean rooms.

These approaches have been used for fabricating tissue engineering scaffolds with control

over features such as pore geometry, size, distribution and spatial geometry. For example,

microfabricated approaches have been used to directly engineer the microvasculature

within tissue engineering scaffolds by micromolding biocompatible polymers such as

 poly(lactide-co-glycolide) (PLGA) and poly(glyceride sebacate) (PGS) . In this approach,

a network of microfluidic channels that mimic the tissue microvasculature are fabricated

from PLGA or PGS. By stacking multiple layers of these microfabricated plates, tissue

engineered scaffolds can be fabricated with nanoscale control. Other approaches, such

as the layer by layer deposition of cells and proteins using microfluidic channels,

microsyringe deposition of PLGA polymer, and photopolymerization within microfluidic

channels have been used to generate 3D structures with controlled geometries and

 properties (Figure 2a). The miniaturization of these technologies can be performed to

generate scaffolds with sub-100 nm features, such as grooves, pores and surface patterns.

Bottom-up approaches based on molecular self-assembly of small building

 blocks have also been used to generate tissue engineering scaffolds. Research into self 

assembly of amphiphilic peptides has shown that they can self-assemble to form

hydrogels for tissue engineering. Self-assembled scaffolds can be easily functionalized by

incorporating peptide sequences that direct cell behavior directly into the buildup

molecule. For example, self-assembled gels were fabricated that directed neural stem cell

differentiation to neurons and repressed astrocyte differentiation without exogenous

growth factors. These gels were made from peptides that expressed isoleucine-

lysinevaline-alanine-valine (IKVAV, an amino acid sequence found in laminin) and self-

assembled to form nanofibers. Similar approaches have been used for other tissues such

as cartilage, bone and cardiac applications, and show great promise in tissue engineering.

Microfabrication and nanofabrication approaches have also been used to modify

surface properties with resolutions as small as 50 nm for controlling cell behavior. For 

Page 13: NANO TECHNOLOGY IN TISSUE ENGINEERING

8/7/2019 NANO TECHNOLOGY IN TISSUE ENGINEERING

http://slidepdf.com/reader/full/nano-technology-in-tissue-engineering 13/17

Page 14: NANO TECHNOLOGY IN TISSUE ENGINEERING

8/7/2019 NANO TECHNOLOGY IN TISSUE ENGINEERING

http://slidepdf.com/reader/full/nano-technology-in-tissue-engineering 14/17

One amazing breakthrough announced recently was the engineering of spinal cord

receptor tissue. This is the tissue that is damaged when someone has a spinal cord injury.

It is the tissue that sends the messages from the brain down the spinal cord to give

instructions on movement. It is thought that through carbon nanotechnology this tissue

can be fined tuned and injected into a spinal cord victim’s area of injury. This tissue may

grow and link with the undamaged receptors thus completing the link. With the spinal

cord receptor tissue intact it will be able to transmit the messages from the brain for your 

legs to walk. This is all being developed with carbon nano-materials and nanotechnology.

In the future, with carbon based nano-materials and carbon based nanotechnology,

will we have stronger, faster athletes? We be able to tissue engineer hearts and lung that

are bigger? Will this create a super race of humans? One with almost super human power like being able to run faster and farther, jump higher, and hit a baseball farther than

anyone has ever done. Will athletes be tested for engineered parts, like they are now

  being tested for steroids. One can only imagine, but with the use of carbon based

nanotechnology tissue engineering there may be no limits.

RECENT DEVELOPMENTS

Building on an enzyme found in nature, researchers have created a nanoscalecoating for surgical equipment, hospital walls, and other surfaces which safely eradicates

methicillin resistant Staphylococcus aureus (MRSA), the bacteria responsible for 

antibiotic resistant infections.

There is a system where the surface contains an enzyme that is safe to handle,

doesn’t appear to lead to resistance, doesn’t leach into the environment, and doesn’t clog

up with cell debris. The MRSA bacteria come in contact with the surface, and they’re

killed.”In tests, 100 percent of MRSA in solution were killed within 20 minutes of 

contact with a surface painted with latex paint laced with the coating.

The new coating marries carbon nanotubes with lysostaphin, a naturally occurring

enzyme used by non-pathogenic strains of Staph bacteria to defend against

staphylococcus aureus, including MRSA. The resulting nanotube-enzyme “conjugate”

Page 15: NANO TECHNOLOGY IN TISSUE ENGINEERING

8/7/2019 NANO TECHNOLOGY IN TISSUE ENGINEERING

http://slidepdf.com/reader/full/nano-technology-in-tissue-engineering 15/17

can be mixed with any number of surface finishes — in tests, it was mixed with ordinary

latex house paint.

Unlike other antimicrobial coatings, it is toxic only to MRSA, does not rely on

antibiotics, and does not leach chemicals into the environment or become clogged over 

time. It can be washed repeatedly without losing effectiveness and has a dry storage shelf 

life of up to six months.

CONCLUSIONS AND RESEARCH THAT WILL IMPACT FUTURE

DEVELOPMENTS

Tissue engineering, in general, is an area with a large number of techniques or 

 products still in the research stage. Given the importance of small-scale structures, and

cell-cell interaction, nanotechnology could make a significant contribution to the tissue

engineering field as techniques become better developed. Scaffolds could potentially be

used for gene transfer or seeded with genetically modified cells, to introduce genetically

modified cells to a patient suffering from a particular genetic condition. Conversely, gene

therapy could be used as an aid to tissue engineering, to stimulate tissue growth (for 

example, by stimulating growth factors).

Tissue engineering does not necessarily eliminate the problem of compatibility

and rejection. If an individuals own cells are used then there shouldn’t be an issue, but

this method would be more expensive than one that would allow large-scale mass

 production. While Europe tends to use autologous cells, the USA does not. 50,000 heart

transplant candidates die annually in the USA while waiting for transplants. Given that

the number of donors will never be enough to meet the demand, engineering new organs

seems the ‘easiest’ solution. In 1997 a human ear was grown on the back of a mouse,

using tissue engineering. In 2002 sections of rabbit penis were grown in a lab, implanted

into rabbits and successfully used to mate. But both of these examples were relatively

simple tissues and further progress in creating whole organs since has made little

 progress beyond the laboratory stage. For complex organs such as the heart or liver a way

has to be found to recreate the multiple functions they carry out. One of the main

 problems in constructing larger tissues is ensuring that all cells receive a sufficient supply

of nutrients. Though a vascular supply can be grown into a scaffold, there is the risk that

Page 16: NANO TECHNOLOGY IN TISSUE ENGINEERING

8/7/2019 NANO TECHNOLOGY IN TISSUE ENGINEERING

http://slidepdf.com/reader/full/nano-technology-in-tissue-engineering 16/17

cells in the interior will die before it reaches them. However, some advances have been

made in animal trials, and, as mentioned previously, nanopatterning could be used to help

direct cells into forming vascular systems. But, unless there is some radical new

technique developed, it is likely that whole organ transplants are likely to remain

theoretical for a number of years at least.Worldwide, stem cells are currently of extreme

interest. Within the last year there have been reports of stem cells being used as

 pacemakers, to repair retinas, to help cure spinal problems and to treat Parkinson’s. With

stem cells lies the possibility that unlimited numbers of any type of cell could be

 produced for use in tissue engineering, but there are still problems with their use. How

they function is not yet fully understood, which makes controlling their differentiation

difficult. There are also difficulties in isolating stem cells. Embryonic stem cells have

more potential for producing a greater variety of cell types (while adult stem cells are

more restricted), but there are more ethical problems associated with the use of these.

There are currently various restrictions in using stem cells – particularly for commercial

ventures (compared with research and academic institutes).

 Nanotechnology is an emerging field that is potentially changing the way we treat

diseases through drug delivery and tissue engineering. However, significant challenges

remain in pushing this field into clinically viable therapies. For drug delivery, the design

and testing of novel methods of controlling the interaction of nano- technology.

Other tissue engineering projects now being tested are growing and developing of 

lung and heart tissue. One day you may be able to have a heart or lungs grown and stored

at a tissue farm. When you are in need of a transplant because of disease or a car accident

it will be ready for transplant. These tissue engineering farms will rely on carbon nano-

materials for the growth and development of transplants. Carbon nanotechnology will

 become an established and growing field in years to come.

Our life expectancy will change drastically with the use of carbon nanotechnology

and tissue engineering. Some people think we may be able to live forever. If you believe

in God, as I do, is this going against him. I do not think so. All throughout the bible

 people are said to live hundreds of years, a good example is Methuselah, who lived to be

Page 17: NANO TECHNOLOGY IN TISSUE ENGINEERING

8/7/2019 NANO TECHNOLOGY IN TISSUE ENGINEERING

http://slidepdf.com/reader/full/nano-technology-in-tissue-engineering 17/17

969 years old. I also do not think it is us that is creating life, God is giving us

exceptionally smart scientists with a drive for knowledge. This knowledge, along with the

application of carbon nanotechnology will hopefully benefit all of mankind.