Usage of Hydrogels, Solution Polymerization - Term Paper Example

Hydrogels Introduction A gel is a substantially dilute crosslinked system that exhibits a no-flow property when in its steady Hydrogel (or Aquagel) is a subcategory of colloidal gels that exists as a network of polymer chains with water as the primary dispersion medium. They display thixotropy, that is, the property of transforming into a fluid when agitated, but resolidifying when allowed to rest [1]. Though hydrogels are mostly liquid by weight, they are water-insoluble and behave like solids due to their three-dimensional crosslinked network that spans the volume of the liquid medium. 2. Synthesis of a polymeric material A hydrogel construction can be described as a three-dimensional jetty is made up of linear polymer chains with covalent connections, which are in turn connected together by further cross-connections. These cross-connections could be covalent, ionic grafts or crystal sections [2]. Hydrogels form due to polarity and hydrophilic nature of polar groups existing between the polymer chains cross-connections that render it insoluble. There are several known methods of synthesizing hydrogels, some of which are explained below. 2.1. Solution Polymerization: A simple method of constructing hydrogels is by crosslinking water-soluble polymers (with functional groups like -OH, -COOH, -NH2) in solution. In solution co-polymerization reactions, ionic or neutral monomers are mixed with a multi-functional crosslinking agent. The reaction is initiated thermally using UV-light, or by a redox initiator system. The solvent serves as heat sink and minimizes temperature control problems. The reaction is carried out in an organic solvent to prevent water from reacting with the crosslinking agent. Once crosslinked, the resultant hydrogels are washed with distilled water to remove any unreacted monomers, crosslinking agent, and the initiator. Equation 1 shows one such solution polymerization reaction conducted on 2-hydroxyethylmethacrylate monomers to form a hydrogel. Equation 1 [21]: Aqueous free-radical polymerization of 2-hydroxyethylmethacrylate (HEMA) monomers crosslinked by dimethacrylates to form the corresponding hydrogel. This solution crosslinking method is often advantageous since the starting material used can be a well-characterized, purified polymer, and the crosslinking conditions required are mild enough to be carried out in the presence of an active agent. For example, poly (2-hydroxyethyl methacrylate) hydrogels are prepared from hydroxyethyl methacrylate by this method, using ethylene glycol dimethacrylate as the crosslinking agent [3]. The hydrogels synthesized can be made pH- sensitive or temperature-sensitive as required by incorporating methacrylic acid or N-isopropylacrylamide [4] as monomers. 2.2. Polymerization by Irradiation: Ionizing radiation, such as Co-γ or electron beams, can also be used to crosslink solutions of water-soluble polymers to prepare the hydrogels of unsaturated compounds. Radicals form on the polymer chains when the aqueous polymer solution is irradiated. Also, hydroxyl radicals form due to the radiolysis of water molecules, which also attack the polymer chains, resulting in the formation of macro-radicals [5]. Covalent bonds are then formed from the recombination of the macro-radicals on different chains, and finally a crosslinked structure is synthesized. This has the advantage of introducing fewer chemicals to the system and produces relatively pure, residue-free hydrogels, but it often leaves a troublesome sol fraction and possibly degradation products behind [6]. During radiation, polymerization macro-radicals can interact with oxygen, and therefore, radiation is performed in an inert atmosphere using nitrogen or argon gas. Polymers crosslinked by radiation method to form hydrogels include poly(vinyl alcohol), poly(ethylene glycol), and poly(acrylic acid) [7]. 2.3. Polymerization by Ionic Crosslinking: Most covalent crosslinking agents are toxic even in small quantities. To overcome this problem and avoid the purification step, hydrogels are often synthesized by reversible ionic crosslinking. Chitosan, a polycationic polymer can react with positively charged components (ions or molecules) forming a network of ionic bridges between the polymeric chains, as shown in Figure 1. In contrast to covalent crosslinking, no auxiliary molecules such as catalysts are required in ionic crosslinking [9]. Chitosan is also known to form polyelectrolyte complex with poly(acrylic acid). The polyelectrolyte complex undergoes slow erosion, hence producing a more biodegradable material than covalently crosslinked hydrogels [10]. 2.4. Suspension Polymerization: In suspension polymerization, a monomer solution is dispersed in a non-solvent, resulting in the formation of fine droplets that are stabilized by the addition of a stabilizer. The polymerization is initiated by the thermal decomposition of free radicals. The prepared micro-particles are then washed to remove unreacted monomers, crosslinking agent, and initiator. This method is generally used for the preparation of spherical hydrogel micro-particles with size-range of 1 µm to 1mm [8]. Hydrogel micro-particles of poly(vinyl alcohol) and poly(hydroxy ethyl methacrylate) are produced by this method. 2.5. Bulk Polymerization: This technique is used to synthesize monolithic blocks of hard hydrogels. The products generally have a dense amorphous structure, and a porous structure when carried out in the presence of water soluble crystals [5]. Figure 2 shows a dense polyHEMA hydrogel structure produced in bulk polymerization with a 5% crosslinking agent content. The Trommsdorf effect (an uncontrolled acceleration of the reaction) is seen when glassy hydrogels are produced via bulk polymerization using free radical reactions. The auto-acceleration is tamed by reducing the initiator concentration, lowering the reaction temperature, and improving the heat transfer between the reaction vessel and the temperature bath [5]. 2.6. Click Chemistry Techniques: Traditional hydrogel synthesis relies upon uncontrolled crosslinking methods such as radical chemistry, which often results in poorly defined products and increases the difficulty in relating the network structure to a hydrogel’s final physical properties. Click chemistry is a branch introduced by K. B. Sharpless which describes chemistry tailored to generate substances quickly and reliably by joining small units together [11] (shown in Equation 2). Equation 2 [24]: A click reaction showing the 1, 3-dipolar cycloaddition of azides to alkynes This concept can be utilized for the construction of hydrogels with controlled architecture and improved mechanical performance due to its complete specificity and high fidelity in the presence of a wide variety of functional groups [12]. Cell-responsive hydrogels can be synthesized through this technique by the crosslinking of cysteine-based peptides with vinyl sulfone-functionalized multi-armed poly(ethylene glycol) (PEG) macromers [13]. 3. Characterization techniques There are many reasons which necessitate the need to characterize a hydrogel. The primary aim of characterization of hydrogels is to improve a material’s performance. Such characterization is linked to the parameters that are related to the desirable properties of the material (like strength, impermeability, toughness, etc.). Forensic analysis, recycling and reclamation, and failure analysis of components require the identification of the polymer type. A hydrogel’s characterization requires the specification of several parameters, since it consists of a statistical distribution of chains of varying lengths, and each chain consists of monomer residues that in turn affect its properties. Some of the major techniques used for the characterization purposes are explained in this section. 3.1. Structural Analysis: Hydrogels typically consist of a molecular distribution of varying sizes and shapes. Chromatographic methods like Viscometry and Size-Exclusion Chromatography (depicted in Figure 3) in combination with Low-Angle Laser Light Scattering (LALLS) [14] are used to determine a hydrogel’s molecular weight distribution and degree of long chain branching. Hydrogels with short chain branching require Analytical Temperature Rising Elution Fractionation (ATREF) techniques to reveal how the short chain branches are distributed over the various molecular weights. Gel Permeation Chromatography is used to determine number-average molecular weight, weight-average molecular weight, molar mass distribution and polydispersity through the separation of different molecular mass fraction samples [14]. Ultraviolet-visible spectroscopy uses electromagnetic radiation of the lowest wavelength to identify molecules with conjugated molecular structures like carbonyl groups [15]. Techniques such as Wide Angle X-ray Scattering (WAXS), Small Angle X-ray Scattering (SAXS), and Small Angle Neutron Scattering (SANS) are used to determine the orientation and crystalline structure of hydrogels accurately. The precise 3D arrangement of atoms in molecules (tacticity, cis-trans isomer discrimination, etc.) can de deduced using Nuclear Magnetic Resonance and Raman Spectroscopy [15]. 3.2. Thermal Analysis: An important technique for hydrogel characterization is thermal analysis, in particular, Differential Scanning Calorimetry (DSC). In DSC, the difference in the amount of heat required to increase the temperature of a sample and reference are measured as a function of temperature. It is used to measure thermal properties of a hydrogel like specific heat capacity, melting/ boiling point, latent heat, enthalpies, etc. For semi-crystalline hydrogels, it aids in measuring crystallinity. Dielectric spectroscopy (or impedance spectroscopy) is used to measure conductivity and other dielectric properties of a material as a function of frequency through the interaction of an external field with the electric dipole moment of the sample (often expressed by permittivity) [16]. Thermogravimetry is used to evaluate the thermal stability, monomer content, onset of thermal degradation and absorbed moisture levels of a hydrogel [15]. 3.3. Mechanical Analysis: Dynamic Mechanical Spectroscopy (DMS) is used to measure the complex modulus of a hydrogel and aids in predicting the behavioural properties of the material that is dependent on the modulus. In this technique, a material is exposed to a periodical deformation which can be in tensile, compression or bending in nature. (Generally, torsional deformations are preferred as they produce a linear response more readily.) The deformation (strain) is then described as a linear function of the applied force (stress), and the resultant coefficient is called the Young’s modulus. This modulus is measured as a function of the frequency of the deformation and/or the temperature of the experiment. Tests for uniaxial tensile and functional swelling properties can also be conducted to determine the Youngs modulus and Poissons ratio at varying degrees of swelling equilibrium of hydrogels. Force response tests are carried out to determine the force exerted by a cylindrical hydrogel structure on compression plates held at fixed displacement. Particle Image Velocimetry can be adapted to investigate the deformation rates at various times within hydrogel structures during volumetric swelling by the measurement of varying velocity fields [17]. 3.4. Morphological Analysis: Morphological parameters are immensely important for the mechanical properties of a material at a nanoscale. Scanning Electron Microscopy, Scanning Probe Microscopy, and Transmission Electron Microscopy in combination with staining techniques are utilized to optimize the morphology of hydrogel materials, in particular the arrangement of the crystal lamellae and non-crystalline regions. A sample of this is shown in Figure 5. The long periods of semi-crystalline hydrogels are measured using Small Angle X-ray Scattering (SAXS) technique. The chemical composition of a hydrogel is often determined by surface analysis and spectroscopic techniques in conjunction with chemical analysis. Electron Spectroscopy for Chemical Analysis (ESCA) yields information like composition and bonding state about the surface [15]. By determining the morphology, thermo-mechanical properties of a hydrogel can be predicted and studied. 4. Applications Hydrogels are commonly used in tissue engineering as scaffolds containing human cells for tissue engineering [6]. Poly(vinyl alcohol) is used to synthesize such hydrogels for biomedical applications. They can also be used as delivery systems for bioactive molecules because of their high biocompatibility and similar physical properties as that of living tissue. (This is due to their high water content, soft and rubbery consistency, and low interfacial tension with water or biological fluids [8].) Environmentally sensitive hydrogels, which have the ability to sense changes of pH, temperature, or concentration of metabolite, and release their load as result of such a change are used as sustained-release delivery systems for medicinal purposes (explained in Figure 6). Anionic hydrogels are used for site-specific drug delivery of therapeutic proteins to the large intestine, and cationic hydrogels are used to develop self-regulated insulin delivery systems that release insulin in response to changing glucose concentration [8]. Hydrogels that respond to specific molecules (like glucose or antigens) are used as biosensors. The presence of ionisable functional groups like carboxylic acid, sulfonic acid and amine groups renders a hydrogel more hydrophilic and results in high water uptake and consequent swelling [18]. This swelling behaviour of responsive hydrogels makes them of use in microactuator applications and fluid microsystems like micropumps. Temperature and pH-responsive hydrogels can be applied for flow control in microfluidic devices without any external power supply [19]. In fibre optics communications, a soft hydrogel is used to fill the plastic tubes containing the fibres. The gel protects the fibres against mechanical damage when the tubes are bent around corners during installation, and provides water insulation if the buffer tube is breached. Moreover, hydrogels act as processing aids during the construction of optical cables and keep the fibres central as the tube material is extruded around them. Another application of hydrogels is the production of soft contact lenses, which perfectly adapt to the global ocular curvature and allow atmospheric O2 to reach the cornea by dissolving in the water of the lens and transporting it by diffusions till the permeability limits close to those of a hypothetical lens of distilled water are reached [20]. This helps in guaranteeing increased comfort to the user. Hydrogels are also used in commercial products like disposable diapers, sanitary napkins, contact lenses (silicone hydrogels, polyacrylamides), water gel explosives, breast implants and wound dressings which need to create or maintain a moist environment. 5. Conclusion This paper outlines the major synthesis and characterization techniques related to hydrogels, and their applications in a variety of fields. 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Chapter 8: Strategies for Regeneration and Repair in the Injured Central Nervous System. In Indwelling Neural Implants: Strategies for Contending with the In Vivo Environment; Reichert, William M., Ed. CRC Press: Boca Raton, 2008. Read More