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Smart polymers, stimuli-responsive polymers or functional polymers are high-performance
polymers A polymer (; Greek ''poly-'', "many" + '' -mer'', "part") is a substance or material consisting of very large molecules called macromolecules, composed of many repeating subunits. Due to their broad spectrum of properties, both synthetic an ...
that change according to the environment they are in. Such materials can be sensitive to a number of factors, such as
temperature Temperature is a physical quantity that expresses quantitatively the perceptions of hotness and coldness. Temperature is measured with a thermometer. Thermometers are calibrated in various temperature scales that historically have relied on ...
,
humidity Humidity is the concentration of water vapor present in the air. Water vapor, the gaseous state of water, is generally invisible to the human eye. Humidity indicates the likelihood for precipitation, dew, or fog to be present. Humidity dep ...
, pH, chemical compounds, the
wavelength In physics, the wavelength is the spatial period of a periodic wave—the distance over which the wave's shape repeats. It is the distance between consecutive corresponding points of the same phase on the wave, such as two adjacent crests, tr ...
or intensity of light or an
electrical Electricity is the set of physical phenomena associated with the presence and motion of matter that has a property of electric charge. Electricity is related to magnetism, both being part of the phenomenon of electromagnetism, as described ...
or
magnetic field A magnetic field is a vector field that describes the magnetic influence on moving electric charges, electric currents, and magnetic materials. A moving charge in a magnetic field experiences a force perpendicular to its own velocity and t ...
and can respond in various ways, like altering color or transparency, becoming conductive or permeable to water or changing shape ( shape memory polymers). Usually, slight changes in the environment are sufficient to induce large changes in the polymer's properties.


Applications

Smart polymers appear in highly specialized applications and everyday products alike. They are used for
sensors A sensor is a device that produces an output signal for the purpose of sensing a physical phenomenon. In the broadest definition, a sensor is a device, module, machine, or subsystem that detects events or changes in its environment and sends ...
and
actuators An actuator is a component of a machine that is responsible for moving and controlling a mechanism or system, for example by opening a valve. In simple terms, it is a "mover". An actuator requires a control device (controlled by control signal) ...
such as artificial muscles , the production of
hydrogels A gel is a semi-solid that can have properties ranging from soft and weak to hard and tough. Gels are defined as a substantially dilute cross-linked system, which exhibits no flow when in the steady-state, although the liquid phase may still dif ...
,
biodegradable Biodegradation is the breakdown of organic matter by microorganisms, such as bacteria and fungi. It is generally assumed to be a natural process, which differentiates it from composting. Composting is a human-driven process in which biodegradati ...
packaging, and to a great extent in
biomedical engineering Biomedical engineering (BME) or medical engineering is the application of engineering principles and design concepts to medicine and biology for healthcare purposes (e.g., diagnostic or therapeutic). BME is also traditionally logical sciences ...
. One example is a polymer that undergoes
conformational change In biochemistry, a conformational change is a change in the shape of a macromolecule, often induced by environmental factors. A macromolecule is usually flexible and dynamic. Its shape can change in response to changes in its environment or oth ...
in response to pH change, which can be used in
drug delivery Drug delivery refers to approaches, formulations, manufacturing techniques, storage systems, and technologies involved in transporting a pharmaceutical compound to its target site to achieve a desired therapeutic effect. Principles related to dr ...
. Another is a humidity-sensitive polymer used in self-adaptive wound dressings that automatically regulate moisture balance in and around the wound. The nonlinear response of smart polymers is what makes them so unique and effective. A significant change in structure and properties can be induced by a very small stimulus. Once that change occurs, there is no further change, meaning a predictable all-or-nothing response occurs, with complete uniformity throughout the polymer. Smart polymers may change conformation, adhesiveness or
water Water (chemical formula ) is an inorganic, transparent, tasteless, odorless, and nearly colorless chemical substance, which is the main constituent of Earth's hydrosphere and the fluids of all known living organisms (in which it acts as ...
retention properties, due to slight changes in pH,
ionic strength The ionic strength of a solution is a measure of the concentration of ions in that solution. Ionic compounds, when dissolved in water, dissociate into ions. The total electrolyte concentration in solution will affect important properties such ...
, temperature, ultrasound, or other triggers. For example, Kubota et al designed and loaded ultrasound-responsive hydrogel microbeads with silica nanoparticles that were released under ultrasonic stimulation. Another factor in the effectiveness of smart polymers lies in the inherent nature of polymers in general. The strength of each molecule's response to changes in stimuli is the composite of changes of individual
monomer In chemistry, a monomer ( ; ''mono-'', "one" + '' -mer'', "part") is a molecule that can react together with other monomer molecules to form a larger polymer chain or three-dimensional network in a process called polymerization. Classification ...
units which, alone, would be weak. However, these weak responses, compounded hundreds or thousands of times, create a considerable force for driving biological processes. The pharmacy industry has been directly related to the polymer’s advances. In this field, polymers are playing a significant role, and their advances are helping entire populations around the world. The human body is a machine with a complex system and works as a response to chemical signals. Polymers play the role of drug delivery technology that can control the release of therapeutic agents in periodic doses. Polymers are capable of molecular recognition and directing intracellular delivery. Smart polymers get into the field to play and take advantage of molecular recognition and finally produced awareness systems and polymer carriers to facilitate drug delivery in the body system.


Stimuli

Several polymer systems respond to temperature, undergoing a
lower critical solution temperature The lower critical solution temperature (LCST) or lower consolute temperature is the critical temperature below which the components of a mixture are miscible in all proportions. The word ''lower'' indicates that the LCST is a lower bound to a tem ...
phase transition. One of the better-studied such polymers is poly(N-isopropylacryamide), with a transition temperature of approximately 33 °C. Several
homologous Homology may refer to: Sciences Biology *Homology (biology), any characteristic of biological organisms that is derived from a common ancestor *Sequence homology, biological homology between DNA, RNA, or protein sequences * Homologous chrom ...
N-
alkyl In organic chemistry, an alkyl group is an alkane missing one hydrogen. The term ''alkyl'' is intentionally unspecific to include many possible substitutions. An acyclic alkyl has the general formula of . A cycloalkyl is derived from a cycloal ...
acrylamide Acrylamide (or acrylic amide) is an organic compound with the chemical formula CH2=CHC(O)NH2. It is a white odorless solid, soluble in water and several organic solvents. From the chemistry perspective, acrylamide is a vinyl-substituted primary a ...
s also show LCST behavior, with the transition temperature depending on the length of the
hydrophobic In chemistry, hydrophobicity is the physical property of a molecule that is seemingly repelled from a mass of water (known as a hydrophobe). In contrast, hydrophiles are attracted to water. Hydrophobic molecules tend to be nonpolar and, ...
side chain. Above their transition temperature, these polymers become insoluble in water. This behavior is believed to be
entropy Entropy is a scientific concept, as well as a measurable physical property, that is most commonly associated with a state of disorder, randomness, or uncertainty. The term and the concept are used in diverse fields, from classical thermodyna ...
driven.


Classification and chemistry

Currently, the most prevalent use for smart polymers in
biomedicine Biomedicine (also referred to as Western medicine, mainstream medicine or conventional medicine)
is for specifically targeted drug delivery. Since the advent of timed-release
pharmaceuticals A medication (also called medicament, medicine, pharmaceutical drug, medicinal drug or simply drug) is a drug used to diagnose, cure, treat, or prevent disease. Drug therapy (pharmacotherapy) is an important part of the medical field and ...
, scientists have been faced with the problem of finding ways to deliver drugs to a particular site in the body without having them first degrade in the highly
acidic In computer science, ACID ( atomicity, consistency, isolation, durability) is a set of properties of database transactions intended to guarantee data validity despite errors, power failures, and other mishaps. In the context of databases, a s ...
stomach environment. Prevention of adverse effects on healthy bone and tissue is also an important consideration. Researchers have devised ways to use smart polymers to control the release of drugs until the delivery system has reached the desired target. This release is controlled by either a chemical or physiological trigger. Linear and matrix smart polymers exist with a variety of properties depending on reactive
functional groups In organic chemistry, a functional group is a substituent or moiety in a molecule that causes the molecule's characteristic chemical reactions. The same functional group will undergo the same or similar chemical reactions regardless of the rest ...
and side chains. These groups might be responsive to pH, temperature,
ionic strength The ionic strength of a solution is a measure of the concentration of ions in that solution. Ionic compounds, when dissolved in water, dissociate into ions. The total electrolyte concentration in solution will affect important properties such ...
,
electric Electricity is the set of physical phenomena associated with the presence and motion of matter that has a property of electric charge. Electricity is related to magnetism, both being part of the phenomenon of electromagnetism, as described b ...
or
magnetic fields A magnetic field is a vector field that describes the magnetic influence on moving electric charges, electric currents, and magnetic materials. A moving charge in a magnetic field experiences a force perpendicular to its own velocity and to ...
, and light. Some polymers are reversibly cross-linked by noncovalent bonds that can break and reform depending on external conditions.
Nanotechnology Nanotechnology, also shortened to nanotech, is the use of matter on an atomic, molecular, and supramolecular scale for industrial purposes. The earliest, widespread description of nanotechnology referred to the particular technological goal o ...
has been fundamental in the development of certain nanoparticle polymers such as
dendrimers Dendrimers are highly ordered, branched polymeric molecules. Synonymous terms for dendrimer include arborols and cascade molecules. Typically, dendrimers are symmetric about the core, and often adopt a spherical three-dimensional morphology. The ...
and
fullerenes A fullerene is an allotrope of carbon whose molecule consists of carbon atoms connected by single and double bonds so as to form a closed or partially closed mesh, with fused rings of five to seven atoms. The molecule may be a hollow sphere, ...
, that have been applied for drug delivery. Traditional drug encapsulation has been done using
lactic acid Lactic acid is an organic acid. It has a molecular formula . It is white in the solid state and it is miscible with water. When in the dissolved state, it forms a colorless solution. Production includes both artificial synthesis as well as natur ...
polymers. More recent developments have seen the formation of lattice-like matrices that hold the drug of interest integrated or entrapped between the polymer strands. Smart polymer matrices release drugs by a chemical or physiological structure-altering reaction, often a hydrolysis reaction resulting in cleavage of bonds and release of drug as the matrix breaks down into
biodegradable Biodegradation is the breakdown of organic matter by microorganisms, such as bacteria and fungi. It is generally assumed to be a natural process, which differentiates it from composting. Composting is a human-driven process in which biodegradati ...
components. The use of natural polymers has given way to artificially synthesized polymers such as
polyanhydrides {{No footnotes, date=July 2019 Polyanhydrides are a class of biodegradable polymers characterized by anhydride bonds that connect repeat units of the polymer backbone chain. Their main application is in the medical device and pharmaceutical industry ...
,
polyesters Polyester is a category of polymers that contain the ester functional group in every repeat unit of their main chain. As a specific material, it most commonly refers to a type called polyethylene terephthalate (PET). Polyesters include natura ...
,
polyacrylic acid Poly(acrylic acid) (PAA; trade name Carbomer) is a polymer with the formula (CH2-CHCO2H)n. It is a derivative of acrylic acid (CH2=CHCO2H). In addition to the homopolymers, a variety of copolymers and crosslinked polymers, and partially deproto ...
s, poly(methyl methacrylates), poly(phthalaldehyde), and
polyurethanes Polyurethane (; often abbreviated PUR and PU) refers to a class of polymers composed of organic units joined by carbamate (urethane) links. In contrast to other common polymers such as polyethylene and polystyrene, polyurethane is produced from ...
.
Hydrophilic A hydrophile is a molecule or other molecular entity that is attracted to water molecules and tends to be dissolved by water.Liddell, H.G. & Scott, R. (1940). ''A Greek-English Lexicon'' Oxford: Clarendon Press. In contrast, hydrophobes are ...
,
amorphous In condensed matter physics and materials science, an amorphous solid (or non-crystalline solid, glassy solid) is a solid that lacks the long-range order that is characteristic of a crystal. Etymology The term comes from the Greek language ...
, low-molecular-weight polymers containing
heteroatoms In chemistry, a heteroatom () is, strictly, any atom that is not carbon or hydrogen. Organic chemistry In practice, the term is usually used more specifically to indicate that non-carbon atoms have replaced carbon in the backbone of the molecul ...
(i.e., atoms other than carbon) have been found to degrade fastest. Scientists control the rate of drug delivery by varying these properties thus adjusting the rate of degradation. A graft-and-block
copolymer In polymer chemistry, a copolymer is a polymer derived from more than one species of monomer. The polymerization of monomers into copolymers is called copolymerization. Copolymers obtained from the copolymerization of two monomer species are some ...
is two different polymers grafted together. A number of patents already exist for various combinations of polymers with different reactive groups. The product exhibits properties of both individual components which adds a new dimension to an intelligent polymer structure and may be useful for certain applications. Cross-linking hydrophobic and hydrophilic polymers result in the formation of micelle-like structures that can protectively assist drug delivery through
aqueous An aqueous solution is a solution in which the solvent is water. It is mostly shown in chemical equations by appending (aq) to the relevant chemical formula. For example, a solution of table salt, or sodium chloride (NaCl), in water would ...
medium until conditions at the target location cause the simultaneous breakdown of both polymers. A graft-and-block approach might be useful for solving problems encountered by the use of a common bioadhesive polymer,
polyacrylic acid Poly(acrylic acid) (PAA; trade name Carbomer) is a polymer with the formula (CH2-CHCO2H)n. It is a derivative of acrylic acid (CH2=CHCO2H). In addition to the homopolymers, a variety of copolymers and crosslinked polymers, and partially deproto ...
(PAA). PAA adheres to mucosal surfaces but will swell and degrade rapidly at pH 7.4, resulting in the rapid release of drugs entrapped in its matrix. A combination of PAAc with another polymer that is less sensitive to changes at neutral pH might increase the residence time and slow the release of the drug, thus improving bioavailability and effectiveness.
Hydrogels A gel is a semi-solid that can have properties ranging from soft and weak to hard and tough. Gels are defined as a substantially dilute cross-linked system, which exhibits no flow when in the steady-state, although the liquid phase may still dif ...
are polymer networks that do not dissolve in water but swell or collapse in changing aqueous environments. They are useful in
biotechnology Biotechnology is the integration of natural sciences and engineering sciences in order to achieve the application of organisms, cells, parts thereof and molecular analogues for products and services. The term ''biotechnology'' was first used b ...
for phase separation because they are reusable or
recyclable Recycling is the process of converting waste materials into new materials and objects. The recovery of energy from waste materials is often included in this concept. The recyclability of a material depends on its ability to reacquire the p ...
. New ways to control the flow, or catch and release of target compounds, in hydrogels, are being investigated. Highly specialized hydrogels have been developed to deliver and release drugs into specific tissues. Hydrogels made from PAAc are especially common because of their bioadhesive properties and tremendous absorbency.
Enzyme immobilization An immobilized enzyme is an enzyme, with restricted mobility, attached to an inert, insoluble material—such as calcium alginate (produced by reacting a mixture of sodium alginate solution and enzyme solution with calcium chloride). This can pro ...
in hydrogels is a fairly well-established process. Reversibly cross-linked polymer networks and hydrogels can be similarly applied to a biological system where the response and release of a drug are triggered by the target molecule itself. Alternatively, the response might be turned on or off by the product of an
enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different molecule ...
reaction. This is often done by incorporating an enzyme, receptor or
antibody An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and Viral disease, viruses. The antibody recognizes a unique m ...
, that binds to the molecule of interest, into the hydrogel. Once bound, a
chemical reaction A chemical reaction is a process that leads to the chemical transformation of one set of chemical substances to another. Classically, chemical reactions encompass changes that only involve the positions of electrons in the forming and break ...
takes place that triggers a reaction from the hydrogel. The trigger can be oxygen, sensed using
oxidoreductase In biochemistry, an oxidoreductase is an enzyme that catalyzes the transfer of electrons from one molecule, the reductant, also called the electron donor, to another, the oxidant, also called the electron acceptor. This group of enzymes usually ...
enzymes or a pH-sensing response. An example of the latter is the combined entrapment of
glucose oxidase The glucose oxidase enzyme (GOx or GOD) also known as notatin (EC number 1.1.3.4) is an oxidoreductase that catalyses the oxidation of glucose to hydrogen peroxide and D-glucono-δ-lactone. This enzyme is produced by certain species of fungi and ...
and
insulin Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the ''INS'' gene. It is considered to be the main anabolic hormone of the body. It regulates the metabol ...
in a pH-responsive hydrogel. In the presence of glucose, the formation of
gluconic acid Gluconic acid is an organic compound with molecular formula C6H12O7 and condensed structural formula HOCH2(CHOH)4COOH. It is one of the 16 stereoisomers of 2,3,4,5,6-pentahydroxyhexanoic acid. In aqueous solution at neutral pH, gluconic acid fo ...
by the enzyme triggers the release of insulin from the hydrogel. Two criteria for this technology to work effectively are enzyme stability and rapid kinetics (quick response to the trigger and recovery after removal of the trigger). Several strategies have been tested in
type 1 diabetes Type 1 diabetes (T1D), formerly known as juvenile diabetes, is an autoimmune disease that originates when cells that make insulin (beta cells) are destroyed by the immune system. Insulin is a hormone required for the cells to use blood sugar f ...
research, involving the use of similar types of smart polymers that can detect changes in
blood glucose level Glycaemia, also known as blood sugar level, blood sugar concentration, or blood glucose level is the measure of glucose concentrated in the blood of humans or other animals. Approximately 4 grams of glucose, a simple sugar, is present in the blo ...
s and trigger the production or release of insulin. Likewise, there are many possible applications of similar hydrogels as
drug delivery Drug delivery refers to approaches, formulations, manufacturing techniques, storage systems, and technologies involved in transporting a pharmaceutical compound to its target site to achieve a desired therapeutic effect. Principles related to dr ...
agents for other conditions and diseases.


Other Applications

Smart polymers are not just for drug delivery. Their properties make them especially suited for bioseparations. The time and costs involved in purifying
proteins Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respondi ...
might be reduced significantly by using smart polymers that undergo rapid reversible changes in response to a change in medium properties. Conjugated systems have been used for many years in physical and affinity separations and
immunoassays An immunoassay (IA) is a biochemical test that measures the presence or concentration of a macromolecule or a small molecule in a solution through the use of an antibody (usually) or an antigen (sometimes). The molecule detected by the immunoassa ...
. Microscopic changes in the polymer structure are manifested as
precipitate In an aqueous solution, precipitation is the process of transforming a dissolved substance into an insoluble solid from a super-saturated solution. The solid formed is called the precipitate. In case of an inorganic chemical reaction leading ...
formation, which may be used to aid the separation of trapped proteins from solution. These systems work when a protein or other molecule that is to be separated from a mix, forms a bioconjugate with the polymer and precipitates with the polymer when its environment undergoes a change. The precipitate is removed from the media, thus separating the desired component of the conjugate from the rest of the mixture. Removal of this component from the conjugate depends on the recovery of the polymer and a return to its original state, thus hydrogels are very useful for such processes. Another approach to controlling biological reactions using smart polymers is to prepare
recombinant proteins Recombinant DNA (rDNA) molecules are DNA molecules formed by laboratory methods of genetic recombination (such as molecular cloning) that bring together genetic material from multiple sources, creating sequences that would not otherwise be foun ...
with built-in polymer binding sites close to
ligand In coordination chemistry, a ligand is an ion or molecule ( functional group) that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's ele ...
or cell binding sites. This technique has been used to control ligand and cell binding activity, based on a variety of triggers including temperature and light. Smart polymers play an essential part in the technology of self-adaptive wound dressings. The dressing design presents proprietary super-absorbent synthetic smart polymers immobilized in the 3-dimensional fiber matrix with added hydration functionality achieved by embedding hydrogel into the core of the material. The dressing's mode of action relies on the ability of the polymers to sense and adapt to the changing humidity and fluid content in all areas of the wound simultaneously and to automatically and reversibly switch from absorption to hydration. The smart polymer action ensures the active synchronized response of the dressing material to changes in and around the wound to support the optimal moist healing environment at all times.


Future applications

It has been suggested that polymers might be developed that can learn and self-correct behavior over time. Although this might be a far-distant possibility, there are other more feasible applications that appear to be coming in the near future. One of these is the idea of smart toilets that analyze urine and help identify health problems. In
environmental biotechnology Environmental biotechnology is biotechnology that is applied to and used to study the natural environment. Environmental biotechnology could also imply that one try to harness biological process for commercial uses and exploitation. The Internati ...
, smart
irrigation Irrigation (also referred to as watering) is the practice of applying controlled amounts of water to land to help grow crops, landscape plants, and lawns. Irrigation has been a key aspect of agriculture for over 5,000 years and has been dev ...
systems have been also proposed. It would be incredibly useful to have a system that turns on and off, and controls
fertilizer A fertilizer (American English) or fertiliser (British English; see spelling differences) is any material of natural or synthetic origin that is applied to soil or to plant tissues to supply plant nutrients. Fertilizers may be distinct from ...
concentrations, based on soil
moisture Moisture is the presence of a liquid, especially water, often in trace amounts. Small amounts of water may be found, for example, in the air (humidity), in foods, and in some commercial products. Moisture also refers to the amount of water vapo ...
, pH, and
nutrient levels A nutrient is a substance used by an organism to survive, grow, and reproduce. The requirement for dietary nutrient intake applies to animals, plants, fungi, and protists. Nutrients can be incorporated into cells for metabolic purposes or exc ...
. Many creative approaches to targeted drug delivery systems that self-regulate based on their unique
cell Cell most often refers to: * Cell (biology), the functional basic unit of life Cell may also refer to: Locations * Monastic cell, a small room, hut, or cave in which a religious recluse lives, alternatively the small precursor of a monastery w ...
ular surroundings, are also under investigation. There are obvious possible problems associated with the use of smart polymers in
biomedicine Biomedicine (also referred to as Western medicine, mainstream medicine or conventional medicine)
. The most worrisome is the possibility of
toxicity Toxicity is the degree to which a chemical substance or a particular mixture of substances can damage an organism. Toxicity can refer to the effect on a whole organism, such as an animal, bacterium, or plant, as well as the effect on a subs ...
or incompatibility of artificial substances in the body, including degradation products and
byproducts A by-product or byproduct is a secondary product derived from a production process, manufacturing process or chemical reaction; it is not the primary product or service being produced. A by-product can be useful and marketable or it can be consid ...
. However, smart polymers have enormous potential in biotechnology and biomedical applications if these obstacles can be overcome.


See also

*
Smart materials Smart materials, also called intelligent or responsive materials, are designed materials that have one or more properties that can be significantly changed in a controlled fashion by external stimuli, such as stress, moisture, electric or magneti ...
*
Programmable matter Programmable matter is matter which has the ability to change its physical properties (shape, density, moduli, conductivity, optical properties, etc.) in a programmable fashion, based upon user input or autonomous sensing. Programmable matter is ...
*
Sensors A sensor is a device that produces an output signal for the purpose of sensing a physical phenomenon. In the broadest definition, a sensor is a device, module, machine, or subsystem that detects events or changes in its environment and sends ...
*
Actuators An actuator is a component of a machine that is responsible for moving and controlling a mechanism or system, for example by opening a valve. In simple terms, it is a "mover". An actuator requires a control device (controlled by control signal) ...
* Artificial muscles


References

{{DEFAULTSORT:Smart Polymer Polymer chemistry Smart materials