Nanotechnology applications in medicine and dentistry. J Investigative Clin Dent 2011;2:81-8

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原文題目(出處): Nanotechnology applications in medicine and dentistry. J Investigative Clin Dent 2011;2:81-8

原文作者姓名: Jyoti Gupta

通訊作者學校: South Campus, Panjab University, Chandigarh, India.

報告者姓名(組別): R2黃明德

報告日期: 100.09.30

內文:

Introduction

 The term ‘‘nanotechnology’’ was coined by Professor Kerie E. Drexler, a lecturer and researcher of nanotechnology.

 The prefix ‘‘nano’’ means 10-9 or one billionth of a unit.

 The nanoscale is approximately 1000 times smaller than a microscale, which is approximately 1/80000 the diameter of a human hair..

 Nanotechnology in medicine has been recently reviewed (2002–present) from various perspectives relative to the human molecule–tissue interface, and has led to the emergence of a new field called nanomedicine.

 This is the science and technology of diagnosing, treating, and preventing disease and traumatic injury in order to relieve pain and preserve and improve human health through the use of nanoscale-structured materials, biotechnology, and genetic engineering, and eventually, complex molecular machine systems and nanorobots.

 Once one considers other potential applications of nanotechnology to medicine, it is not difficult to imagine the impact on nanodentistry.

 The development of nanodentistry will make possible the maintenance of near-perfect oral health through the use of nanomaterials and biotechnology, including tissue engineering and nanorobotics.

Nanotechnology in medicine

 The potential applications of nanotechnology in medicine are vast. These include imaging and diagnostics, targeted drug delivery, nano-enabled therapies, and tissue engineering.

Diagnostics

 The ultimate goal is to identify diseases at the earliest stage possible, ideally at the level of a single cell.

 Nanotechnology-on-a-chip is a dimension of lab-on-a-chip technology. Magnetic nanoparticles bound to a suitable antibody are used to label specific molecules, structures or microorganisms.

 Gold nanoparticles tagged with short segments of DNA can be used for the detection of genetic sequence in a sample. Multicolor optical coding for biological assays has been achieved by embedding different-sized quantum dots into polymeric

microbeads. Quantum dots are semiconductor nanoparticles that have unique optical and electrical properties.

 Fluorescent quantum dots will provide a brighter, more precise, and longer lasting alternative. Quantum dots can be injected into cells or attached to proteins in order to track, label, or identify specific biomolecules, and these offer ultimate detection

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sensitivity.

Drug delivery

 It delivers drugs to specific cells using nanoparticles.

 The overall drug consumption and side-effects can be lowered significantly by depositing the active agent in the morbid region only and in no higher dose than needed. This highly selective approach reduces cost and human suffering.

 One of the most highly publicized areas of nanomedicine research involves gold nanoshells to detect and treat cancerous tumors.

 Nanoshells are particles of silica (glass) that are completely coated with gold, made up of a few million atoms. They can be produced in a range of sizes, with diameters smaller than 100 nm to as large as several hundred nanometers. When injected into the blood stream, they naturally congregate at the tumor sites, and therefore, no additional targeting is necessary.

 In order to feed their growth, tumors create many blood vessels (neoangiogenesis) very quickly, so the vessels are often defective, allowing the nanoshells to slip through vascular ‘‘leaks’’ and gain access to the tumor.

 Detecting and targeting tumors by exploiting their surrounding vascular defects is known as enhanced permeability and retention effect. A nanoshell captures light and focuses it around itself. By manipulating the size of the nanoshells, it is possible to change the way they absorb light. The goal in cancer detection and therapy is to

‘‘tune’’ the nanoshells to interact with near-infrared light (NIR).When exposed to NIR, the nanoshells act like a swarm of fireflies’ and light up the area where they have congregated (i.e. tumor sites).

 The area around the nanoshells heats up and the tumor ‘‘cooks’’ until it is ablated..

Tissue engineering

 Nanotechnology can play a pivotal role in the development of cost-effective therapies for in situ tissue regeneration. This ‘‘nanobiomimetic’’ strategy depends on three basic elements:

(a) intelligent biomaterials;

(b) bioactive signaling molecules;

(c) cells.

 These biomaterials are designed to react positively to changes in the immediate environment, stimulating specific regenerative events at the molecular level, directing cell proliferation, cell differentiation, and extracellular matrix production and organization.

 The sequential signaling of bioactive molecules is necessary for the fabrication and repair of tissues. Nano-assisted technologies should enable the sequential delivery of proteins, peptides, and genes to mimic nature’s signaling cascade.

 Nano-assisted technologies will aid in achieving two main objectives: (a) to identify signaling systems, in order to leverage the self-healing potential of endogenous adult stem cells; and (b) to develop efficient targeting systems for stem cell therapies.

Nanorobots in surgery

 Surgical nanorobots could be introduced into the body through the vascular system

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or at the ends of catheters into various vessels and other cavities in the human body.

 A surgical nanorobot, programmed or guided by a human surgeon. Such a device could perform various functions, such as searching for pathology and then diagnosing and correcting lesions by nanomanipulation.

 For example, a rapidly vibrating (100 Hz) micropipette with a <1 micron tip diameter has been used to completely cut dendrites from single neurons without damaging cell viability.

 Axotomy of roundworm neurons was performed by femtosecond laser surgery, after which the axons functionally regenerated. A femtolaser acts like a pair of

nanoscissors by vaporizing tissue locally, while leaving adjacent tissue unharmed.

Nanorobotics in gene therapy

 Medical nanorobots can readily treat genetic diseases by comparing the molecular structures of both DNA and proteins found in the cell to known or desired reference structures.

 Any irregularities can then be corrected, or desired modifications can be edited in place.

Overview of nanostructures for dental applications

Nanoparticles

 Nanoparticles (molecular units typically defined as having diameters of between 0.1 and 100 nm) of various compositions represent the most widespread use of

nanoscale units in dentistry.

 They are currently being used in resin-based composite restorations (RBC).

Considerable research related to nanocomposites is focused on tailoring newer types of silane bonding agents for optimal use with nanoparticles in RBC.

Nanorods

 Nanorods are of particular interest in a restorative context. Chen et al. have synthesized enamel prism-like hydroxyapatite (HA) nanorods that exhibit self-assembly properties.

 Since they are similar to the enamel rods that make up the basic crystalline structure of dental enamel, nanorods could contribute to a practical artificial approximation of such a naturally occurring structure.

Nanospheres

 Nanospheres are explored in restorative systems in conjunction with calcium phosphate deposition and amelogenin nanochain assembly to mimic the nanoprocesses already inherent in natural tooth development.

Nanotubes

 Nanotubes of various types have been investigated for dental applications. Titanium oxide nanotubes have been shown in vitro to accelerate the kinetics of HA

formation.

 More recently, modified singlewalled carbon nanotubes (SWCNT) have been shown to improve the flexural strength of RBC. These SWCNT had silicon dioxide applied to them in conjunction with specialized organosilane bonding agents.

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Nanofibers

 Polymer nanofiber materials have been studied as drug-delivery systems, scaffolds for tissue engineering, and filters.

 More recently, nanofibers have been used to generate ceramics containing HA and fluor-HA.

 Nanofibrillar silicate crystals have also been recently studied in the reinforcement of dental composites.

Dendrimers and dendritic copolymers

 Dendrimers and dendritic copolymers have been studied, albeit less extensively than other nanostructures, in relation to dental composite applications. Combinations of specific polymers to optimize efficacy of restorative applications have been

reported.

Nanotechnology applications in dentistry

 Applications of nanotechnology in the dental field are varied, including the

advanced visualization of dental structures, improvement in the physical properties of materials, mimicking the natural processes in tooth development, and in the use of specialized nanomachines called nanorobots to perform routine dental procedures.

Nanocharacterization in dentistry.

 Studying dental structures and surfaces from a nanoscale perspective might lead to better understanding the structure and function–physiological relationship of dental surfaces.

 Using nanocharacterization tools for oral fluids, such as saliva, a variety of oral diseases can be understood at the molecular and cellular levels, and thereby prevented.

 Advanced nanocharacterization techniques are relevant for the elucidation of underlying physiochemical mechanisms favoring biocompatibility and osseointegration of dental implants

Nanomaterials

 Various nanostructures are manipulated together to either modify the existing dental materials or produce the newer better alternatives.

Nanocomposites

 The ever-shrinking size of the nanoparticles in RBC ceramic restorative systems continues in a progression that might be envisioned as ‘‘mimicking’’ actual tooth structure.

 The nanofiller has esthetic and strength advantages over conventional microfilled and hybrid RBC systems, primarily in terms of smoothness, polishability, and

precision of shade characterization, plus flexural strength and microhardness, similar to those of the better-performing posterior RBC..

Restorative materials advances

 The polyhedral oligomeric silsesquioxane (POSS) molecule can be used in dental applications to: (a) improve adhesion at the interface between the restorative material and the tooth structure; (b) reduce tooth sensitivity through sealing the tubules with POSS nano-sized molecules; and (c) provide structural reinforcement, toughness, and processability.

 Ormoceris (Fraunhofer-Gesellschaft, Munich, Germany) is an acronym for organically modified ceramics. Ormocers represent a new technology based on

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sol-gel synthesis using particles comprising silicones, organic polymers, and ceramic glasses that is applicable to dental composites.

 Ormocer composite technology is used in conjunction with nanoparticle fillers, such as ZrO2, that are widely used in nanocomposite restorative systems. Nano-sized CaPO4-incorporated composites are used in the optimal delivery of molecules that facilitate tooth structure remineralization and forestall caries is an active area of nanostructure-based research.

 Recent studies by Xu et al. have evaluated the incorporation of nano-sized CaPO4 particles with RBC, with a resulting improvement in stress-bearing capacity, as well as ion release that could inhibit caries.

Materials for endodontic regeneration

 Teeth with degenerated and necrosed pulps are routinely saved by root canal therapy.

Although current treatment modalities offer high levels of success for many conditions, an ideal form of therapy might consist of regenerative approaches, in which diseased or necrotic pulp tissues are removed and replaced with healthy pulp tissues to revitalize teeth.

 In their study, Fioretti et al. showed that a-MSH (melanocortin peptides) possess anti-inflammatory properties and also promote the proliferation of pulpal fibroblasts.

They reported the first use of nanostructured and functionalized multilayered films containing a-MSH as a new active biomaterial for endodontic regeneration.

Esthetic materials

 With the combination of finishing and polishing procedures, a nanotechnology liquid polish application might provide a more glossy surface for resin composite restorations.

Solutions

 Nanosolutions produce unique and dispersible nanoparticles, which can be used in bonding agents. This ensures homogeneity and ensures that the adhesive is perfectly mixed every time.

Impression materials

 Nanofillers are integrated in vinylpolysiloxanes, producing a unique addition of siloxane impression materials. The material has better flow, improved hydrophilic properties, and enhanced detail precision.

Dental biomimetics

 The most interesting venue for speculation on the nanorestoration of tooth structure is that of nanotechnology mimicking processes that occur in nature (biomimetics), such as the formation of dental enamel.

 A recent in vitro study by Wang et al. further elucidated mechanisms of interaction among amelogenin nanospheres, nanoparticles, and nanorods at critical points during the HA crystal-growth process. The results offer further evidence for cooperation in interfacial matching between organic and inorganic nanophases that might resemble processes that occur in actual enamel formation.

 whole-replacement tooth that includes both mineral and cellular components – that is, complete dentition replacement therapy – should become feasible within the time and economic constraints of a typical office visit, through the use of an affordable desktop manufacturing facility, which would fabricate the new tooth, in the dentist’s office.

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Nanorobotics

 New potential treatment opportunities in dentistry might include local anesthesia, dentition renaturalization, permanent hypersensitivity cures, complete orthodontic realignments during a single office visit, covalently bonded diamondized enamel, and continuous oral health maintenance using mechanical dentifrobots.

 These nanorobot functions might be controlled by an onboard nanocomputer that executes pre-programmed instructions in response to local sensor stimuli.

Alternatively, the dentist might issue strategic instructions by transmitting orders directly to in vivo nanorobots via acoustic signals or other means.

Local nano-anesthesia

 To induce oral anesthesia in the era of the nanodentist, professionals will install a colloidal suspension containing millions of active analgesic micrometersized dental nanorobot particles on the patient’s gingivae. After contacting the surface of the crown or mucosa, the moving nanorobots reach dentin by migrating into the gingival sulcus and passing painlessly through the lamina propria or the 1- or 3-lm-thick layer of loose tissue at the cementodental junction.

 On reaching the dentin, the nanorobots enter dentinal tubular holes that are 1–4 lm in diameter and proceed towards the pulp.

 Once installed in the pulp, having established control over nerve impulse traffic, the analgesic dental nanorobots might be commanded by the dentist to shut down all sensitivity in the tooth that requires treatment. When the dentist passes the icon for the desired tooth on the handheld controlled display monitor, the tooth is

immediately anesthetized.

 After the oral procedure is completed, the dentist orders the nanorobots via the same acoustic data links to restore all sensation, relinquish control of nerve traffic, to retract from the tooth via a similar path.

 This analgesic technique is patient friendly, as it reduces anxiety, needle phobia, and most importantly, is a quick and completely reversible action.

Dental hypersensitivity

 Dentin hypersensitivity is a pathological phenomenon. It is caused by pressure-transmitted hydrodynamically to the pulp.

 Mainly hypersensitive teeth have dentinal tubules with surface densities that are eight times higher than those of non-sensitive teeth. Dental nanorobots can

selectively and precisely occlude the specific tubules within 1 min, offering patients a quick and permanent cure.

Orthodontic nanorobots

 Orthodontic nanorobots can directly manipulate the periodontal tissue, including gingival, periodontal ligament, cemental, and alveolar tissues, allowing rapid and painless tooth straightening, rotating, and vertical repositioning within minutes to hours.

Tooth durability and appearance

 In nanodentistry, sapphire, a nanostructured composite material, increases tooth durability and appearance. Upper enamel layers are replaced by coherently bonded artificial materials, such as sapphire. This material has 100–200 times the hardness and failure strength than ceramic. Like enamel, sapphire is somewhat susceptible to

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acid corrosion. Sapphire has the best-standard whitening sealant and can be used as a cosmetic alternative.

Dentifrobots

 Properly configured dentifrobots could identify and destroy pathogenic bacteria residing in the plaque and elsewhere, while allowing the 500 or so species of harmless oral microflora to flourish in a healthy ecosystem.

 Dentifrobots would also provide a continuous barrier to halitosis, since bacterial putrefaction is the central metabolic process involved in oral malodor.

Renaturalization procedures

 Dentition renaturalization procedures might become a popular addition to typical dental practice, providing perfect treatment methods for esthetic dentistry. This trend might begin with patients who desire to have their old dental amalgams excavated and their teeth remanufactured with native biological materials.

 Demand will grow for full coronal renaturalization procedures, in which all fillings, crowns, and other 20th century modifications to the visible dentition are removed, with the affected teeth remanufactured to become indistinguishable from the original teeth.

Safety issues

 While nanomaterials and nanotechnologies are expected to yield numerous health and health-care advances, such as more targeted methods of delivering drugs, new cancer therapies, and methods of early detection of diseases, they also might have unwanted effects.

 The increased rate of absorption is the main concern associated with manufactured nanoparticles. When materials are made into nanoparticles, their surface area:

volume ratio increases.

 The greater specific surface area (surface area/unit weight) might lead to increased rates of absorption through the skin, lungs, or digestive tract, and might cause unwanted effects to the lungs, as well as other organs.

 Apart from what occurs if non-degradable or slowly degradable nanoparticles accumulate in organs, another concern is their potential interaction with biological processes inside the body; because of their large surface, nanoparticles, upon

exposure to tissue and fluids, will immediately absorb onto their surface some of the macromolecules they encounter. However, the particles must be absorbed in

sufficient quantities in order to pose a health risk.

 To address such concerns, the Swedish Karolinska Institute conducted a study in which various nanoparticles were introduced to human lung epithelial cells. The results, released in 2008, showed that iron oxide nanoparticles caused little DNA damage and were non-toxic. Zinc oxide nanoparticles were slightly worse. Titanium dioxide caused only DNA damage; carbon nanotubes caused DNA damage at low levels. Copper oxide was found to be the worst offender, and was the only

nanomaterial identified by the researchers as a clear health risk.

 The National Institute for Occupational Safety and Health is conducting research on how nanoparticles interact with the body’s systems and how workers might be exposed to nano-sized particles in the manufacturing or industrial use of nanomaterials.

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Conclusion

 Nanodevices cannot be seen, yet possess powerful capabilities. They have the potential to bring about significant benefits, such as improved health, better use of natural resources, and reduced environmental pollution. At present, applied

nanotechnology to medicine and dentistry is in its infancy, with most of the research at the basic science level, as the field attempts to organize itself.

 As such, viable clinical applications are still years away, but despite this the current pace of development is impressive. Applications of nanotechnologies in medicine are especially promising, and such areas as disease diagnosis, drug delivery targeted at specific sites in the body, and molecular imaging are being intensively

investigated.

 Nanodentistry still faces many significant challenges in realizing its tremendous potential. Basic engineering problems from precise positioning and assembly of molecularscale parts to economical mass production techniques to biocompatibility, and the simultaneous coordination of the activities of a large number of independent micrometer- scale robots is being investigated.

 Nanodentistry will give a new vision to comprehensive oral health care, as trends of oral health have been changing to more preventive intervention than a curative and restorative procedure. This science might sound like a fiction now, but nanodentistry has strong potential to revolutionize dentists to diagnose and treat diseases in the future.

 However, at the same time, there will be increased social issues of public acceptance, ethics, regulation, and human safety that must be addressed before molecular

nanotechnology can enter the modern medical and dental armamentarium.

題號 題目

1 When will we see the first practical applications of nanotechnology?

(According to Christine Peterson, president of the Foresight Institute) (A) 10 and 30 years from now

(B) 50 years from now (C) 70 years from now (D) 100 years from now 答案

(A)

出處: Nanodentistry. Fact or fiction? J Am Dent Assoc. 2000 Nov;131(11):1567-8.

題號 題目

2 The nanodentistry can use for (A) Dental caries

(B) Tooth sensitivity (C) Oral cancer (D) all of above 答案

(D )

出處:Nanocharacterization in dentistry.Int J Mol Sci. 2010 Jun 17;11(6):2523-45

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