materials Review A Review on the Design and Hydration Properties of Natural Polymer-Based Hydrogels Abdalla H. Karoyo and Lee D. Wilson * Department of Chemistry, University of Saskatchewan, 110 Science Place, Saskatoon, SK S7N 5C9, Canada; [email protected] * Correspondence: [email protected]; Tel.: +1-306-966-2961 Abstract: Hydrogels are hydrophilic 3D networks that are able to ingest large amounts of water or biological fluids, and are potential candidates for biosensors, drug delivery vectors, energy harvester devices, and carriers or matrices for cells in tissue engineering. Natural polymers, e.g., cellulose, chitosan and starch, have excellent properties that afford fabrication of advanced hydrogel materials for biomedical applications: biodegradability, biocompatibility, non-toxicity, hydrophilicity, thermal and chemical stability, and the high capacity for swelling induced by facile synthetic modification, among other physicochemical properties. Hydrogels require variable time to reach an equilibrium swelling due to the variable diffusion rates of water sorption, capillary action, and other modalities. In this study, the nature, transport kinetics, and the role of water in the formation and structural stability of various types of hydrogels comprised of natural polymers are reviewed. Since water is an integral part of hydrogels that constitute a substantive portion of its composition, there is a need to obtain an improved understanding of the role of hydration in the structure, degree of swelling and the mechanical stability of such biomaterial hydrogels. The capacity of the polymer chains to swell in an aqueous solvent can be expressed by the rubber elasticity theory and other thermodynamic contributions; whereas the rate of water diffusion can be driven either by concentration gradient or Citation: Karoyo, A.H.; Wilson, L.D. chemical potential. An overview of fabrication strategies for various types of hydrogels is presented as A Review on the Design and well as their responsiveness to external stimuli, along with their potential utility in diverse and novel Hydration Properties of Natural applications. This review aims to shed light on the role of hydration to the structure and function of Polymer-Based Hydrogels. Materials 2021, 14, 1095. https://doi.org/ hydrogels. In turn, this review will further contribute to the development of advanced materials, 10.3390/ma14051095 such as “injectable hydrogels” and super-adsorbents for applications in the field of environmental science and biomedicine. Academic Editor: Diana Ciolacu Keywords: hydrogels; water; hydration; natural polymers; swelling; structure Received: 5 January 2021 Accepted: 17 February 2021 Published: 26 February 2021 1. Introduction Publisher’s Note: MDPI stays neutral Hydrogels are polymeric materials capable of swelling and maintaining a distinct with regard to jurisdictional claims in 3D structure upon absorption of large amounts of water. The first synthetic hydrogels published maps and institutional affil- were developed in 1954 by Wichterle and Lim [1] using poly-2-hydroxyethyl methacrylate iations. (pHEMA). Soon after this discovery, hydrogels were used in contact lens production [1–3] and have since been used in various applications, including tissue engineering, drug deliv- ery systems, environmental remediation [4,5], agriculture and biosensors [6–10]. Tradition- ally, biomaterial hydrogels were designed mainly by crosslinking polymerization reactions. Copyright: © 2021 by the authors. However, recent advances in the chemistry of biomaterials has revitalized this field of Licensee MDPI, Basel, Switzerland. research. The physicochemical, mechanical, and biocompatible properties of hydrogels This article is an open access article depend on the polymer type, constituent ratio, composition, and the fabrication process. distributed under the terms and Various novel design approaches were reported to afford versatile hydrogel materials with conditions of the Creative Commons enhanced mechanical properties [3–6], super-absorptivity [11,12], super-porosity [13,14], Attribution (CC BY) license (https:// stability [15], and multi-responsive character to external stimuli [16]. In particular, the creativecommons.org/licenses/by/ water sorption property and stability of hydrogels relate to a great number of biomedical 4.0/). Materials 2021, 14, 1095. https://doi.org/10.3390/ma14051095 https://www.mdpi.com/journal/materials Materials 2021, 14, x FOR PEER REVIEW 2 of 36 Materials 2021, 14, 1095 rosity [13,14], stability [15], and multi-responsive character to external stimuli [16]. In2 of par- 35 ticular, the water sorption property and stability of hydrogels relate to a great number of biomedical and technological applications such as drug delivery systems, soft contact andlenses, technological enzyme immobilization, applications such artificial as drug implants, delivery systems,and flocculants soft contact for lenses,the removal enzyme of immobilization,heavy metals [17]. artificial A number implants, of classification and flocculantss of forhydrogels the removal are reported of heavy in metals the literature [17]. A numberas shown of in classifications Figure 1 accounts of hydrogels for a diversity are reported of materials in the literature with variable as shown physicochemical in Figure1 accountsand mechanical for a diversity properties of materials [6,18,19]. with Hydrogel variable systems physicochemical can be categorized and mechanical based proper-on their tiessurface/electrical [6,18,19]. Hydrogel charge systems as ionic can (i.e., be anionic categorized or cationic), based on neutral, their surface/electrical amphoteric (containing charge asboth ionic acidic (i.e., anionicand basic or cationic),groups), or neutral, zwitterionic amphoteric (containing (containing both both anionic acidic and and cationic basic groups),groups). or Similarly, zwitterionic the (containingtype of crosslinking both anionic determines and cationic whet groups).her the hydrogel Similarly, is the physical type of(e.g., crosslinking hydrophobic determines association, whether chain the aggregat hydrogelion, is physicaland hydrogen (e.g., hydrophobic bonding), chemical association, (e.g. chaincovalent aggregation, bonding) or and has hydrogen a dual-network bonding), of crosslinks chemical [19]. (e.g., Hydrogels covalent have bonding) also been or has clas- a dual-networksified based on of their crosslinks structure [19]. as Hydrogels either crysta havelline, also amorphous, been classified or semi-crystalline. based on their On struc- the tureother as hand, either the crystalline, source of amorphous, the polymer or scaffold semi-crystalline. relates to Onthe the formation other hand, of natural, the source syn- ofthetic, the polymer or hybrid scaffold hydrogel relates materials. to the formationHydrogel-forming of natural, natural synthetic, biopolymers or hybrid include hydrogel pro- materials.teins (e.g., Hydrogel-formingcollagen and gelatin) natural and polysaccharides biopolymers include (e.g., starch, proteins cellulose (e.g., collagenand chitosan). and gelatin)In the case and of polysaccharides synthetic hydrogels, (e.g., starch,variou celluloses polymer and materials chitosan). including In the casepHEMA, of synthetic poly(N- hydrogels,isopropyl acrylamide) various polymer (PNIPAM), materials polyacrylamide including pHEMA, (PAA), poly(N-isopropylpolyvinyl alcohol acrylamide)(PVA), poly- (PNIPAM),ethylene glycol polyacrylamide (PEG) and their (PAA), derivatives polyvinyl are alcohol well known (PVA), [7]. polyethylene Synthetic polymer glycol (PEG)hydro- andgels their possess derivatives high water are well sorption/retention known [7]. Synthetic capacity, polymer longer hydrogels shelf-life possess and enhanced high water gel sorption/retentionstrength [20]. By contrast, capacity, bio-based longer shelf-life hydrogels and offer enhanced added gel advantages strength [20 due]. By to contrast,their en- bio-basedhanced biocompatibility hydrogels offer and added biodegradability, advantages due as to well their as enhanced good mechanical biocompatibility strength and and biodegradability,porous structure asimparted well as goodby their mechanical hierarchic strengthal structure and [21]. porous With structure the advances imparted in ma- by theirterials hierarchical science, the structure fabrication [21 of]. composite With the advances hydrogel in materials materials offer science, advanced the fabrication hybrid sys- oftems composite with unique hydrogel physico-mechanical materials offer properti advancedes. hybridIn particular, systems the with synthesis unique and physico- modifi- mechanicalcation of such properties. systems In can particular, be achieved the synthesis via physical and modificationand/or chemical of such means, systems where can pro- be achievedcesses such via as physical crosslinking, and/or grafting, chemical impregna means, wheretion, incorporation, processes such blending, as crosslinking, interpenetra- graft- ing,tion, impregnation, and imprinting incorporation, methods are blending, involved interpenetration, [8]. The feasibility and of imprinting applying bio-based methods are hy- involveddrogels and [8]. Thetheir feasibility modified offorms applying for biomedica bio-basedl hydrogelspurposes (e.g., and theirtissue modified engineering, forms drug for biomedicaldelivery systems, purposes and (e.g., contact tissue lenses), engineering, the envi drugronment delivery (e.g., systems, flocculants and and contact sorbents lenses), for the