Nanocomposite hydrogels (NC gels) are nanomaterial-filled, hydrated, polymeric networks that exhibit higher elasticity and strength relative to traditionally made hydrogels. A range of natural and synthetic polymers are used to design nanocomposite network. By controlling the interactions between nanoparticles and polymer chains, a range of physical, chemical, and biological properties can be engineered. [1] The combination of organic (polymer) and inorganic (clay) structure gives these hydrogels improved physical, chemical, electrical, biological, and swelling/de-swelling properties that cannot be achieved by either material alone. [2] Inspired by flexible biological tissues, researchers incorporate carbon-based, polymeric, ceramic and/or metallic nanomaterials to give these hydrogels superior characteristics like optical properties and stimulus-sensitivity which can potentially be very helpful to medical (especially drug delivery and stem cell engineering) and mechanical fields. [2]
Nanocomposite hydrogels are not to be confused with nanogel , a nanoparticle composed of a hydrogel.
The synthesis of nanocomposite hydrogels is a process that requires specific material and method. These polymers need to be made up of equally spaced out, 30 nm in diameter, clay platelets that can swell and exfoliate in the presence of water. The platelets act as cross-links to modify molecular functions to enable the hydrogels to have superior elasticity and toughness that resembles closely that of biological tissue. [3] Using clay platelets that do not swell or exfoliate in water, using an organic cross-linker such as N,N-methylenebisacrylamide(BIS), mixing of clay and BIS, or preparing nanocomposite hydrogels in a method other than cross-link, will be unsuccessful. [4]
Despite all the specifications, the process of synthesizing nanocomposite hydrogels is simple and because of the flexible nature of the material, these hydrogels can be easily made to come in different shapes such as huge blocks, sheets, thin films, rods, hollow tubes, spheres, bellows and uneven sheets. [5]
Nanocomposite hydrogels are tough, and can withstand stretching, bending, knotting, crushing, and other modifications.
Tensile testings were performed on nanocomposite hydrogels to measure the stress and strain it experiences when elongated under room temperature. The results show that this material can be stretched up to 1000% of its original length. [6]
Hysteresis is used to measure the compression properties of nanocomposite hydrogels, which shows that this material can withstand around 90% compression. This data shows that nanocomposite hydrogels exhibit superior strength relative to conventionally-made hydrogels, which would have broken down under less compression.
The porous network of clay particles enable nanocomposite hydrogels to swell in the presence of water. Swelling (and de-swelling) distinguishes NC gels from conventionally-made hydrogels (OR gels) as it is a property that OR gels lack. The swelling property of NC gels allows them to collect the surrounding aqueous solution instead of being dissolved by it, which helps make them good candidates for drug delivery carriers. [7]
Nanocomposite hydrogels are observed to be temperature sensitive and will change temperature when their surrounding is altered. [8] Inorganic salts, when absorbed, will result in changing the hydrogels to a lower temperature whereas cat-ionic surfactant will shift the temperature the other way. The temperature of these hydrogels are around 40 degrees Celsius, making it a possible candidate for use as biomaterial. [9] The stimulus-sensitivity of hydrogels allow for a responsive release system where the hydrogels can be designed to deliver the drug in response to changes in condition of the body.
Nanocomposite hydrogels that are enforced with carbon-based nanomaterials are mechanically tough and electrically conducive, which make them suitable for use in biomedicine, tissue engineering, drug delivery, biosensing, etc. The electrical conducting property of these hydrogels allow them to mimic the characteristic of nerve, muscle, and cardiac tissues. However, even though these nanocomposite hydrogels demonstrate some functions of human tissue in lab environments, more research is needed to ensure their utility as tissue replacement. [10]
Nanocomposite hydrogels incorporated with polymeric nanoparticles are tailored for drug delivery and tissue engineering. The addition of polymeric nanoparticles gives these hydrogels a reinforced polymeric network that is more stiff and has the ability to enclose hydrophilic and hydrophobic drugs along with genes and proteins. The high stress-absorbing property makes them a potential candidate for cartilage tissue engineering. [10]
Most inorganic nanoparticles used for nanocomposite hydrogels are already present in and necessary for the body, and thus present no negative impacts on the body. Some of them, like calcium and silicon, help with preventing bone loss and skeletal development. Others, like nanoclays, improve the structural formation and characteristics of hydrogels where they acquire self-healing properties, flame retardant structures, elasticity, super gas-barrier membrane, oil-repellence, etc. The unique properties obtained by incorporating nanocomposite hydrogels with inorganic nanoparticles will let researchers work on improving bone-related tissue engineering. [10]
The electrical and thermal conductivity and magnetic property of metals enhance the electrical conductivity and antibacterial property of nanocomposite hydrogels when incorporated. The electrical conducting property is necessary for the hydrogels to start forming functional tissues and be used as imaging agents, drug delivery systems, conductive scaffolds, switchable electronics, actuators, and sensors.[ citation needed ]
Researchers have been looking for a material that can mimic tissue properties to make the tissue engineering process more effective and less invasive to the human body. The porous, interconnecting network of nanocomposite hydrogels, created through cross-link, enable wastes and nutrients to easily enter and exit the structure, and their elastomeric properties let them acquire the desired anatomical shape without needing prior molding. The porous structure of this material would also make the process of drug delivery easier where the pharmaceutical compounds present in the hydrogel can easily escape and be absorbed by the body. Aside from that, researchers are also looking into incorporating nanocomposite hydrogels with silver nanoparticles for antibacterial applications and microorganism elimination in medical and food packing and water treatment. Hydrogels infused with nanoparticles have a number of biological applications, including: tissue engineering, chemical and biological sensing and drug and gene delivery.
As tissue replacements, nanocomposite hydrogels need to interact with cells and form functional tissues. With the incorporated nanoparticles and nanomaterials, these hydrogels can mimic the physical, chemical, electrical, and biological properties of most native tissue. Each type of nanocomposite hydrogels has its own unique properties that let it mimic certain types of animal tissue.
The emergence of nanocomposite hydrogels allow for more site-specific and time-controlled delivery of drugs of different sizes at improved safety and specificity. Depending on the method of inserting drugs into the material, for example, dissolved, encased, or attached, the drug carrier will be named differently: nanoparticles, nanospheres (where the drug is evenly dispersed throughout the polymeric network), or nanocapsules (where the drug is surrounded by a polymer shell structure). [7] The elastomeric nature of this material allows the hydrogels to obtain the shape of the targeted site and thus the hydrogels can be manufactured identically and used on all patients. [11]
Hydrogels are controlled drug delivery agents that can be engineered to have desired properties. [12] Specifically, hydrogels can be designed to release drugs or other agents in response to physical characteristics of the environment like temperature and pH. [12] The responsiveness of hydrogels is a result of their molecular structure and polymer networks. [12]
Hydrogel nanoparticles have a promising future in the drug delivery field. Ideally, drug delivery systems should, “…maximize the efficacy and the safety of the therapeutic agent, delivering an appropriate amount at a suitable rate and to the most appropriate site in the body”. [13] Nanotechnology incorporated within hydrogels has the potential to meet all the requirements of an ideal drug delivery system. Hydrogels have been studied with a variety of nanocomposites including: clay, gold, silver, iron oxide, carbon nanotubes, hydroxyapatite, and tricalcium phosphate. [13]
Nanoparticles, largely due to their size related physical properties, are highly useful as drug delivery agents. They can overcome physiological barriers and reach specific targets. [14] Nanoparticles’ size, surface charge and properties enable them to penetrate biological barriers that most other drug carriers cannot. [14] To become even more specified, nanoparticles can be coated with targeting ligands. [14] The ability of nanoparticles to deliver drugs to specific targets suggests the potential to limit systemic side-effects and immune responses. [15]
The ability of nanoparticles to carry and release drugs is also largely dependent on characteristics which result from the small size and unique surface area to volume ratio of nanoparticles. Nanoparticles can generally carry drugs in two ways: drugs can either be bound to the outside of the nanoparticles or packed within the polymeric matrix of the nanoparticles. [14] Smaller nanoparticles have higher surface area ratios and can thus bind a high quantity of drug, while larger nanoparticles can encapsulate more of the drug within its core. [15] The best method of drug loading is dependent on the structures of the drug to be bound. Also, drug loading can occur as the nanoparticles are produced, or the drugs can be added to pre-existing nanoparticles. [14] The release of drugs, depends largely on the size of the nanoparticle carrying it. Because nanoparticles can be bound to the surface of nanoparticles, which is large relative to the volume of the particles, drugs can be released quickly. In contrast, drugs that are loaded within nanoparticles are released more slowly. [14]
Silver nanoparticles are inserted into the 3D polymeric networks of nanocomposite hydrogels for applications in antibacterial activity and improvement in electrical conductance. The presence of silver ions either stop the respiratory enzyme from transferring electrons to oxygen molecules during respiration or prevent proteins from reacting with thiol groups (-SH) on bacteria membrane, both result in the death of bacteria and microorganism without damaging mammal cells. [16] The size of these silver nanoparticles need to be small enough to pass through the cell membrane and thus further research is required to manufacture them into appropriate sizes.
Some concerns relating to hydrogels infused with nanoparticles are the chances of either bursting, or of incomplete release of drugs. [13] Although hydrogels infused with nanoparticles are speculated to be quite promising methods of drug, protein, peptide, oligosaccharide, vaccine, and nucleic acid delivery, more studies regarding nanotoxicology and safety are required before clinical applications can be pursued. [14] Further, to avoid accumulation, biodegradable gels and nanoparticles are highly desirable. [14]
Biopolymers are natural polymers produced by the cells of living organisms. Like other polymers, biopolymers consist of monomeric units that are covalently bonded in chains to form larger molecules. There are three main classes of biopolymers, classified according to the monomers used and the structure of the biopolymer formed: polynucleotides, polypeptides, and polysaccharides. The Polynucleotides, RNA and DNA, are long polymers of nucleotides. Polypeptides include proteins and shorter polymers of amino acids; some major examples include collagen, actin, and fibrin. Polysaccharides are linear or branched chains of sugar carbohydrates; examples include starch, cellulose, and alginate. Other examples of biopolymers include natural rubbers, suberin and lignin, cutin and cutan, melanin, and polyhydroxyalkanoates (PHAs).
Nanomedicine is the medical application of nanotechnology. Nanomedicine ranges from the medical applications of nanomaterials and biological devices, to nanoelectronic biosensors, and even possible future applications of molecular nanotechnology such as biological machines. Current problems for nanomedicine involve understanding the issues related to toxicity and environmental impact of nanoscale materials.
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 diffuse through this system. A gel has been defined phenomenologically as a soft, solid or solid-like material consisting of two or more components, one of which is a liquid, present in substantial quantity.
A hydrogel is a biphasic material, a mixture of porous, permeable solids and at least 10% by weight or volume of interstitial fluid composed completely or mainly by water. In hydrogels the porous permeable solid is a water insoluble three dimensional network of natural or synthetic polymers and a fluid, having absorbed a large amount of water or biological fluids. These properties underpin several applications, especially in the biomedical area. Many hydrogels are synthetic, but some are derived from nature. The term 'hydrogel' was coined in 1894.
Nanomaterials describe, in principle, materials of which a single unit is sized between 1 and 100 nm.
Sodium polyacrylate (ACR, ASAP, or PAAS), also known as waterlock, is a sodium salt of polyacrylic acid with the chemical formula [−CH2−CH(CO2Na)−]n and has broad applications in consumer products. This super-absorbent polymer (SAP) has the ability to absorb 100 to 1000 times its mass in water. Sodium polyacrylate is an anionic polyelectrolyte with negatively charged carboxylic groups in the main chain. It is a polymer made up of chains of acrylate compounds. It contains sodium, which gives it the ability to absorb large amounts of water. When dissolved in water, it forms a thick and transparent solution due to the ionic interactions of the molecules. Sodium polyacrylate has many favorable mechanical properties. Some of these advantages include good mechanical stability, high heat resistance, and strong hydration. It has been used as an additive for food products including bread, juice, and ice cream.
Nanochemistry is an emerging sub-discipline of the chemical and material sciences that deals with the development of new methods for creating nanoscale materials. The term "nanochemistry" was first used by Ozin in 1992 as 'the uses of chemical synthesis to reproducibly afford nanomaterials from the atom "up", contrary to the nanoengineering and nanophysics approach that operates from the bulk "down"'. Nanochemistry focuses on solid-state chemistry that emphasizes synthesis of building blocks that are dependent on size, surface, shape, and defect properties, rather than the actual production of matter. Atomic and molecular properties mainly deal with the degrees of freedom of atoms in the periodic table. However, nanochemistry introduced other degrees of freedom that controls material's behaviors by transformation into solutions. Nanoscale objects exhibit novel material properties, largely as a consequence of their finite small size. Several chemical modifications on nanometer-scaled structures approve size dependent effects.
Nanocomposite is a multiphase solid material where one of the phases has one, two or three dimensions of less than 100 nanometers (nm) or structures having nano-scale repeat distances between the different phases that make up the material.
Nanofabrics are textiles engineered with small particles that give ordinary materials advantageous properties such as superhydrophobicity, odor and moisture elimination, increased elasticity and strength, and bacterial resistance. Depending on the desired property, a nanofabric is either constructed from nanoscopic fibers called nanofibers, or is formed by applying a solution containing nanoparticles to a regular fabric. Nanofabrics research is an interdisciplinary effort involving bioengineering, molecular chemistry, physics, electrical engineering, computer science, and systems engineering. Applications of nanofabrics have the potential to revolutionize textile manufacturing and areas of medicine such as drug delivery and tissue engineering.
Nanotechnology is impacting the field of consumer goods, several products that incorporate nanomaterials are already in a variety of items; many of which people do not even realize contain nanoparticles, products with novel functions ranging from easy-to-clean to scratch-resistant. Examples of that car bumpers are made lighter, clothing is more stain repellant, sunscreen is more radiation resistant, synthetic bones are stronger, cell phone screens are lighter weight, glass packaging for drinks leads to a longer shelf-life, and balls for various sports are made more durable. Using nanotech, in the mid-term modern textiles will become "smart", through embedded "wearable electronics", such novel products have also a promising potential especially in the field of cosmetics, and has numerous potential applications in heavy industry. Nanotechnology is predicted to be a main driver of technology and business in this century and holds the promise of higher performance materials, intelligent systems and new production methods with significant impact for all aspects of society.
Thiolated polymers – designated thiomers – are functional polymers used in biotechnology product development with the intention to prolong mucosal drug residence time and to enhance absorption of drugs. The name thiomer was coined by Andreas Bernkop-Schnürch in 2000. Thiomers have thiol bearing side chains. Sulfhydryl ligands of low molecular mass are covalently bound to a polymeric backbone consisting of mainly biodegradable polymers, such as chitosan, hyaluronic acid, cellulose derivatives, pullulan, starch, gelatin, polyacrylates, cyclodextrins, or silicones.
Polymer nanocomposites (PNC) consist of a polymer or copolymer having nanoparticles or nanofillers dispersed in the polymer matrix. These may be of different shape, but at least one dimension must be in the range of 1–50 nm. These PNC's belong to the category of multi-phase systems that consume nearly 95% of plastics production. These systems require controlled mixing/compounding, stabilization of the achieved dispersion, orientation of the dispersed phase, and the compounding strategies for all MPS, including PNC, are similar. Alternatively, polymer can be infiltrated into 1D, 2D, 3D preform creating high content polymer nanocomposites.
A nanogel is a polymer-based, crosslinked hydrogel particle on the sub-micron scale. These complex networks of polymers present a unique opportunity in the field of drug delivery at the intersection of nanoparticles and hydrogel synthesis. Nanogels can be natural, synthetic, or a combination of the two and have a high degree of tunability in terms of their size, shape, surface functionalization, and degradation mechanisms. Given these inherent characteristics in addition to their biocompatibility and capacity to encapsulate small drugs and molecules, nanogels are a promising strategy to treat disease and dysfunction by serving as delivery vehicles capable of navigating across challenging physiological barriers within the body.
Smart polymers, stimuli-responsive polymers or functional polymers are high-performance polymers that change according to the environment they are in.
The applications of nanotechnology, commonly incorporate industrial, medicinal, and energy uses. These include more durable construction materials, therapeutic drug delivery, and higher density hydrogen fuel cells that are environmentally friendly. Being that nanoparticles and nanodevices are highly versatile through modification of their physiochemical properties, they have found uses in nanoscale electronics, cancer treatments, vaccines, hydrogen fuel cells, and nanographene batteries.
Self-healing hydrogels are a specialized type of polymer hydrogel. A hydrogel is a macromolecular polymer gel constructed of a network of crosslinked polymer chains. Hydrogels are synthesized from hydrophilic monomers by either chain or step growth, along with a functional crosslinker to promote network formation. A net-like structure along with void imperfections enhance the hydrogel's ability to absorb large amounts of water via hydrogen bonding. As a result, hydrogels, self-healing alike, develop characteristic firm yet elastic mechanical properties. Self-healing refers to the spontaneous formation of new bonds when old bonds are broken within a material. The structure of the hydrogel along with electrostatic attraction forces drive new bond formation through reconstructive covalent dangling side chain or non-covalent hydrogen bonding. These flesh-like properties have motivated the research and development of self-healing hydrogels in fields such as reconstructive tissue engineering as scaffolding, as well as use in passive and preventive applications.
Hydrogels are three-dimensional networks consisting of chemically or physically cross-linked hydrophilic polymers. The insoluble hydrophilic structures absorb polar wound exudates and allow oxygen diffusion at the wound bed to accelerate healing. Hydrogel dressings can be designed to prevent bacterial infection, retain moisture, promote optimum adhesion to tissues, and satisfy the basic requirements of biocompatibility. Hydrogel dressings can also be designed to respond to changes in the microenvironment at the wound bed. Hydrogel dressings should promote an appropriate microenvironment for angiogenesis, recruitment of fibroblasts, and cellular proliferation.
Nanoparticle drug delivery systems are engineered technologies that use nanoparticles for the targeted delivery and controlled release of therapeutic agents. The modern form of a drug delivery system should minimize side-effects and reduce both dosage and dosage frequency. Recently, nanoparticles have aroused attention due to their potential application for effective drug delivery.
Dextran drug delivery systems involve the use of the natural glucose polymer dextran in applications as a prodrug, nanoparticle, microsphere, micelle, and hydrogel drug carrier in the field of targeted and controlled drug delivery. According to several in vitro and animal research studies, dextran carriers reduce off-site toxicity and improve local drug concentration at the target tissue site. This technology has significant implications as a potential strategy for delivering therapeutics to treat cancer, cardiovascular diseases, pulmonary diseases, bone diseases, liver diseases, colonic diseases, infections, and HIV.
Ultrasound-triggered drug delivery using stimuli-responsive hydrogels refers to the process of using ultrasound energy for inducing drug release from hydrogels that are sensitive to acoustic stimuli. This method of approach is one of many stimuli-responsive drug delivery-based systems that has gained traction in recent years due to its demonstration of localization and specificity of disease treatment. Although recent developments in this field highlight its potential in treating certain diseases such as COVID-19, there remain many major challenges that need to be addressed and overcome before more related biomedical applications are clinically translated into standard of care.
