Smart Hydrogels and Their Responsiveness

Introduction

The area of research regarding reactive materials has been improved by the advancement of hydrogels as useful biomaterials [1]. Primarily for contact lenses and tissue scaffolds, hydrogels were established for biomedical use. At the end of the 19th century, hydrogels were initially reported as colloidal gels from inorganic salt. Presently, hydrogel is described as networks of hydrophilic polymers arranged in a three-dimensional structure. These complexes have the capability to bulge and imbibe high quantities of biological liquids or water without scrapping their structure. The polymer chains, for example, amide, carboxyl, amino, and hydroxyl groups, have hydrophilic compounds linked to them which are responsible for their capability to absorb fluids and have the capability to get ionized in the existence of water. Moreover, elasticity and mechanical tolerance, which are crucial characteristics to be regarded when establishing delivery systems, can be enhanced by changing their physical characteristics—for example, mechanical strength, swelling, and surface characteristics through physicochemical reactions. The most frequent application terms related to hydrogels are ‘ocular lens’, ‘wound healing’ [2], ‘super-absorbents’, ‘tissue engineering’, ‘tissue scaffolds’,

‘cell immobilization’, and ‘drug delivery systems’ [3]. The increased growth in the number of publications has been documented in the Science Direct database comprising hydrogels with these keywords. Even though this preponderance can be seen for all earlier described subjects, tissue engineering and drug delivery stand out as they constitute the most of the publications. Remarkably, a similar increase in studies regarding tissue scaffolds, tissue engineering, wound healing, and drug delivery have been reported. The increase in the count of publications containing the term 'hydrogels’ was noted since 2000 [4]. Concurrently, researchers and several industry segments are getting consideration towards hydrogels as for their use as applicative substances [5]. They display swelling/deswelling characteristics connected with the accessibility of water. In the chemical, physical, and biological research, hydrogels of these kinds are associated with their exclusive characteristics that can be related to environmental determinants. Kuhn and co-workers in 1948 established the term ‘smart’ even though the primary research related to hydrogels occurred in 1894 [6]. The most contemporary nomenclature is able to establish distinct triggers (stimuli) to create alterations in organization and function and, thus, acquired significance. The primary publication established was on molecules of poly(acrylic acid) polymer that are able to sustain structural changes in accordance with the cell culture media, pH [7]. However, publications established specific profiles for distinct networks of polymers inclusive of the new smart hydrogels. Drug delivery is able to recognize the persisting stimuli responsiveness via functional, morphological, or structural alterations initiating the discharge of trapped drugs in a coordinated way [8].

There are several measures by which smart hydrogels may be categorized. Degradability, origin (natural or synthetic), and cross-linking methods for self- assembly are among the set of measures that have been utilized to categorize these hydrogels. Chemically covalent bound linking of polymer chains leading to persistent connections gives rise to cross-linked networks within hydrogels [9]. On the contrary, supramolecular forces (non-covalent) are responsible for physically cross- linked structures, resulting in rapid and alterable systems [10]. Other classifications are based on the type of stimuli responsiveness such as physical or chemical stimuli. The pioneer kinds of physical responses consist of pressure, temperature, light, and magnetic or electric fields. Biochemical or chemical stimulants consist of pH, ionic strength, and ions [11]. Biological stimuli indicate response to the molecular processes—for example, catalytic reactions and identification of receptors present on the molecules. In addition, these networks may be formulated to act on single or several stimuli indexes [12]. This chapter concentrates on the fundamental ideas and reactive methods directed by changing the constituents that can impart helpful tools for formulating smart hydrogels in useful ways.

Hydrogels and Responsiveness

Hydrogels have consisted of networks of polymer with three-dimensional (3D) microstructures showing an upper hydration level and exhibiting similarity to natural tissue [2, 3]. 'Smart’ hydrogels could alterably react to outer stimuli such as temperature, pH, pressure, electrical fields, light, solvent, ionic strength, etc. In the initial 1960s, they were one of the primary biomaterials prepared for clinical application by Otto Wichterle and Drahoslav Lim [13]. However, their promising use in several areas has drawn high attention in the past two decades. They may undergo phase transitions or sol-gel phase transitions due to change in surroundings, which can cause drug discharge, engineering of tissue, soft machines, etc. [14, 15]. Out of these uses, these ‘intelligent’ or smart polymers have acted as a crucial part in managing the place of drug release as well as time of delivery and. thus, have resulted in extraordinary development in drug release systems [16].