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Über dieses Buch

This book discusses recent advances in hydrogels, including their generation and applications and presents a compendium of fundamental concepts. It highlights the most important hydrogel materials, including physical hydrogels, chemical hydrogels, and nanohydrogels and explores the development of hydrogel-based novel materials that respond to external stimuli, such as temperature, pressure, pH, light, biochemicals or magnetism, which represent a new class of intelligent materials. With their multiple cooperative functions, hydrogel-based materials exhibit different potential applications ranging from biomedical engineering to water purification systems. This book covers key topics including superabsorbent polymer hydrogel; intelligent hydrogels for drug delivery; hydrogels from catechol-conjugated materials; nanomaterials loaded hydrogel; electrospinning of hydrogels; biopolymers-based hydrogels; injectable hydrogels; interpenetrating-polymer-network hydrogels: radiation- and sonochemical synthesis of micro/nano/macroscopic hydrogels; DNA-based hydrogels; and multifunctional applications of hydrogels. It will prove a valuable resource for researchers working in industry and academia alike.



Chapter 1. Intelligent Hydrogels as Drug Delivery Systems

A drug delivery system (DDS) can be defined as a formulation or a device that facilitates the release of a therapeutic substance in the body. Key parameters of interest in DDS are safety, delivery rate, efficiency, as well as time and place of release of drugs. Lately, hydrogels have attracted significant attention for application in drug delivery. Hydrogels are three-dimensional polymer networks consisting largely of water. They are characterised by a porous structure with porosity, pore size and geometry that can be varied during the hydrogel synthesis. Importantly, due to porous structure they have the ability to incorporate biomolecules.
Katarina Novakovic, Simon Matcham, Amy Scott

Chapter 2. History, Classification, Properties and Application of Hydrogels: An Overview

The term hydrogel was coined in 1894 as it was employed to explain a colloidal gel. The first report on the application of hydrogels was given by Wichterle and Lim in 1960, which was in the biomedical field. Hydrogels generally absorb a large amount of water, and this swelling is responsible for the rubbery and soft properties of hydrogel. Hydrogels have found applications in environmental, biomedical, food, etc., fields. This chapter presents a brief review of hydrogels—basic definition, classifications, preparations and applications. This chapter highlights among others, the application of polysaccharide-based hydrogels in adsorption and dye removal in water treatment.
Sourbh Thakur, Vijay Kumar Thakur, Omotayo Ademola Arotiba

Chapter 3. Macroporous Hydrogels: Preparation, Properties, and Applications

This chapter will be focused on the latest developments in the preparation and properties of macroporous hydrogels (MHGs), and their potential for biomedical applications and separation processes. A wide variety of synthetic and natural polymers have been used for the fabrication of novel macroporous hydrogels. Their morphology could be tailored by the synthesis strategy and synthesis parameters such as initial monomer concentration, cross-linking degree, and gel preparation temperature.
Maria Valentina Dinu, Ecaterina Stela Dragan

Chapter 4. Hydrogel-Based Strategies for Stem Cell Therapy

Stem cells from different sources provide considerable expectation for applications in tissue engineering and regenerative medicine because of their ability to proliferate and differentiate into functional cells. However, poor cell engraftment and survival after transplantation are key factors limiting the current stem cell-based therapy. The utilization of engineered microenvironments with synthetic biomaterials has been progressively successful in controlling the transplanted cells fate by imitating the native stem cell niche. Recently, synthetic 3D extracellular matrices (ECMs) have been extensively explored as scaffolds for tissue regeneration by emulating the components of natural stem cell niche to minimize implanted cell death. For their tunable tissue-like properties, biodegradability, and biocompatibility in all different forms of biomaterials, hydrogels are most normally used as substrates and scaffolds, which serve as a promising cell delivery vehicle to illustrate stem cell biology. Here, we will focus on recent advances in generating hydrogel, as well as the application of hydrogel for stem cell-based therapy. Finally, hydrogel-based controlled-release strategies for improving therapeutic efficiency of stem cells will be discussed.
Shuaiqiang Zhang, Yan Nie, Hongyan Tao, Zongjin Li

Chapter 5. Protein- and Nanoparticle-Loaded Hydrogels Studied by Small-Angle Scattering and Rheology Techniques

In the last decades, hydrogels have been used for controlled loading and release in pharmaceutical applications. In tissue engineering, protein–hydrogel hybrid systems play a critical role in wound healing and tissue growth (Vermonden et al. in Chem Rev 112:2853–2888, 2012). At the same time, the mechanical and morphological properties of hydrogels have been modified and tuned by addition of nanoparticles (Haraguchi et al. in Macromolecules 36:5732–5741, 2003). The mechanical properties of hydrogels are one of their key characteristics. For example in injectable hydrogels, shear-thinning behavior is a defining factor (Guvendiren et al. in Soft Matter 8:260–272, 2012). Furthermore, the rheological behavior of a protein- or nanoparticle-loaded hydrogels may be influenced by the presence of the added compound, especially when the last acts as a cross-linking agent. The multi-scale hierarchical structures produced by hydrogel nanocomposites can be resolved by small-angle neutron scattering and X-ray scattering (SANS and SAXS) in the relevant length scales from 1 to 1000 nm (combined with ultra-small-angle X-ray and neutron scattering: USAXS and USANS). The study of such systems under deformation (e.g., Rheo-SANS) gives invaluable insight into the structural details that define mechanical properties (Shibayama in Polym J 43:18–34, 2011). In this chapter, the recent developments in the field of hydrogels and nanoparticle-loaded-hydrogel systems, based mainly on SANS/SAXS and rheological techniques, are presented. A wide range of experimental realizations and examples of promising hydrogel–protein combinations is covered, and the analyses used to connect the structure–rheology properties are demonstrated in a unifying way.
Aristeidis Papagiannopoulos, Stergios Pispas

Chapter 6. Preparation, Properties and Application of Hydrogels: A Review

Hydrogels are primarily synthesized to retain large amounts of aqueous solution. Depending upon modes of synthesis, the hydrogel materials develop various types of network structure. Recently, popular techniques have been developed for synthesis of hydrogels in the presence of crosslinking agents or multifunctional co-monomer which acts as a crosslinker. It can be categorized according to synthesis techniques, bio-degradability, response to environment and their intended applications. These applications may vary from water retention, conditioner to different aspects of biomedical applications and tissue engineering. Hydrogels contain a number of functional groups which may be utilized as such or modified and used to suit our requirements. In this review article, we have focused on the available synthesis techniques of hydrogels along with their inevitable properties and applications.
Sumit Mishra, Priti Rani, Gautam Sen, Kartick Prasad Dey

Chapter 7. Hydrogel-Based Stimuli-Responsive Functionalized Graft Copolymers for the Controlled Delivery of 5-Fluorouracil, an Anticancer Drug

5-Fluorouracil (5-FU) is a widely used anticancer drug. To minimize the toxic side effects of 5-FU, a suitable drug delivery system (DDS) is needed for its controlled release. In the present chapter, we conducted a study that compared two different controlled-release systems into which 5-FU had been incorporated. The two delivery systems compared were 3-methacryloxy propyl trimethoxy silane-coated magnetic nanoparticles polymerized with glycidyl methacrylate-grafted-maleated cyclodextrin [MPTMS-MNP-poly-(GMA-g-MACD)] and aminated-glycidyl methacrylate-grafted cellulose-grafted polymethacrylic acid-succinyl cyclodextrin [Cell-g-(GMA/en)-PMA-SCD]. The successful formation of DDS and 5-FU loaded DDS was confirmed from FT-IR, XRD, and SEM analyses. Studies including swelling, in vitro release kinetics, drug loading efficiency, encapsulation efficiency, and cytotoxicity were performed to compare the efficiency of the drug carriers. The results suggest that both MPTMS-MNP-poly-(GMA-g-MACD) and Cell-g-(GMA/en)-PMA-SCD may be useful delivery vehicle for the controlled release of 5-FU.
T. S. Anirudhan, P. L. Divya, J. Nima

Chapter 8. Emerging Technology in Medical Applications of Hydrogel

The term hydrogel used to describe the cross-linking long-chain polymer with high content water in the polymer matrix. The water-soluble and swollen property hydrogels were used in medical applications which include targeted delivery of drug, cell carriers, wound healing, and tissue engineering. Owing to different structures and cross-linking methods, the hydrogel has been utilized in biomedical and pharmacy industry. Hence, the preparation methods were important to prepare different types of hydrogels and it is useful in medical application based on their structural properties. The pursuit of this chapter is to concisely describe the recent development of hydrogel preparation, properties, and medical application. Furthermore, biomedical application and current clinical trial studies of hydrogel are summarized briefly.
G. Madhumitha, J. Fowsiya, Selvaraj Mohana Roopan

Chapter 9. Electrospinning of Hydrogels for Biomedical Applications

The field of biomedical applications for hydrogels requires the development of nanostructures with specific controlled diameter and mechanical properties. Nanofibers are ideal candidates for these advanced requirements, and one of the easiest techniques that can produce one-dimensional nanostructured materials in fibrous form is the electrospinning process. This technique provides extremely thin fibers with controlled diameter and highly porous microstructure with interconnected pores. Electrospinning demonstrates extreme versatility allowing the use of different polymers for tailoring properties and applications. It is a simple cost-effective method for the preparation of scaffolds. In this section, we will discuss recent and specific applications with a focus on their mechanisms. As such, we conclude this section with a discussion on perspectives and future possibilities on this field.
Gabriel Goetten de Lima, Sean Lyons, Declan M. Devine, Michael J. D. Nugent

Chapter 10. Self-assembling Hydrogels from pH-Responsive Ionic Block Copolymers

Hydrogels are three-dimensional (3D) soft materials that consist of a solid matrix (usually a three-dimensional network) entrapping high content of water (more than 90 wt%). This remarkable feature makes them suitable for many applications especially in medicine as drug carriers and tissue engineering scaffolds. As far as polymeric matrices are concerned, two main strategies for achieving 3D network structures can be distinguished. The first one relies on the covalent bonding of hydrophilic polymer chains, leading to hydrogels referred as chemical networks. The second approach deals with the self-assembly of tailor-made segmented macromolecules via reversible weak interactions, namely hydrophobic, ionic, π–π staking, and so on, that leads to the so-called self-assembling hydrogels. The use of reversible (physical) cross-links allows the design of “smart” soft materials that can response to their environment (e.g., pH, ionic strength, temperature, shear). This chapter is devoted to the self-assembling hydrogels arising from associative block copolymers bearing ionic or ionogenic blocks, namely polyelectrolytes or polyampholytes. This specific feature endows the hydrogels with responsiveness to pH and ionic strength which make them attractive soft materials for potential biomedical applications.
Constantinos Tsitsilianis

Chapter 11. Cellulose Hydrogels; Fabrication, Properties, and Their Application to Biocompatible and Tissue Engineering

Cellulose hydrogels made of agro-industrial bagasses of sugarcane and other are introduced in this chapter for the fabrication, properties, and their the biocompatible materials with cytocompatibility for tissue engineering. To obtain the cellulose hydrogels, firstly cellulose was regenerated from bagasse wastes by chemical pretreatments and bleaching. The renewable cellulose was converted to hydrogels by phase inversion process under ethanol vapor. To evaluate the biocompatibility, the hydrogel was implanted in the intraperitoneal of mice. The results were shown as small influence of the implanted hydrogel on the growth of mice. The implanted hydrogel was somewhat decreased in the molecular weight in 3–4 weeks, meaning biodegradable materials. However, the hydrogels kept enough mechanical strength in the living body. This indicated that the cellulose hydrogel regenerated waste bagasse showed acceptable biocompatibility and durability in the body. In addition, hydrogels are excellent in regeneration of cytocompatible property for tissue regeneration.
Takaomi Kobayashi

Chapter 12. Injectable Hydrogels for Cartilage Regeneration

Articular cartilage injuries have a limited potential to heal, which over time, may lead to osteoarthritis, an inflammatory and degenerative joint disease associated with activity-related pain, swelling, and impaired mobility. Regeneration and restoration of joint tissue and function remain unmet challenges. Intra-articular injections of therapeutic agents are effective to some extent, but often require multiple injections. In the past decade, injectable hydrogels have emerged as promising biomaterials, due largely to their biocompatibility, tissue extracellular matrix (ECM) mimicry, excellent permeability, and easy adaptation for minimal-invasive procedures. Moreover, hydrogels can be designed as carriers for sustained release of therapeutic agents and protective matrices for cell delivery. This chapter provides an overview of the injectable hydrogel systems currently being applied together with therapeutic drug delivery and/or cell therapy for treatment of cartilage lesions and osteoarthritis.
Cenk Celik, Vishal T. Mogal, James Hoi Po Hui, Xian Jun Loh, Wei Seong Toh

Chapter 13. DNA-Based Hydrogels: An Approach for Multifunctional Bioapplications

DNA-based networks have attracted significant interest in the last decades, due to its hydrophilicity, biocompatibility and stimuli responsiveness. These characteristics make them very suitable for a variety of applications in the biomedical field. In this context, relevant advances on the design and formulation of DNA-based systems as technological devices to be used in clinical applications have been accomplished. In the last few years, particular attention has been focused on the plasmid DNA (pDNA) hydrogels. Biocompatible pDNA gel networks were synthesized by a cross-linking reaction. In order to enhance transfection efficiency and targeting of the systems, transferrin has been included in the protocol of hydrogels preparation. All developed carriers are photodegradable which opens the possibility for the sustained and controlled delivery of different plasmids and anticancer drugs. The cancer treatment approach based on the combination of chemotherapy and specific gene delivery demonstrated to possess stronger ability to weaken the growth and proliferation of tumour cells. The effect is enhanced when transferrin is present in the pDNA hydrogels. This finding is a great achievement and instigates further research focused on the generation of new vectors for the delivery of biopharmaceuticals contributing for the evolution of cancer therapy.
Diana Costa, Artur J. M. Valente, João Queiroz

Chapter 14. Stem Cell Culture on Polymer Hydrogels

The fate of stem cell differentiation is guided by several different factors of the stem cell microenvironment, such as cell culture biomaterial elasticity (physical cues) and cell–biomaterial interactions (biological cues). Mimicking the stem cell microenvironment using polymer hydrogels with optimal elasticities is an excellent strategy for stem cell expansion and differentiation. This chapter describes poly(vinyl alcohol) (PVA) hydrogels grafted with several nanosegments that are designed for the culture and differentiation of human hematopoietic and progenitor cells (hHSPCs), human amniotic fluid stem cells (hAFSCs), and human pluripotent stem cells (hPSCs). The elasticity of the cell culture hydrogels can regulate stem cell adhesion overall, as well as cell phenotype, focal adhesions, and morphology, especially in 2-D culture conditions. The mechano-sensing of cell culture biomaterials by stem cells is typically regulated by integrin-mediated focal adhesion signaling. PVA hydrogels having a storage modulus (E′) of 12–30 kPa were found to be efficient materials for ex vivo hHSPC expansion. We also developed PVA hydrogels grafted with oligopeptides derived from vitronectin (PVA-oligoVN hydrogels), which can be produced to have a variety of stiffnesses, for the xeno-free culture of hPSCs. The ideal stiffness of the PVA-oligoVN hydrogels for hPSC culture was found to be 25.3 kPa. A high concentration of oligoVN (500–1500 µg/mL) should be used to prepare the PVA-oligoVN hydrogels to achieve a sufficient oligoVN surface density to maintain hPSC pluripotency. Optimized stiffness (physical cues) and cell-binding moiety surface density (biological cues) are the key factors for designing hydrogel-based cell culture materials for supporting hPSC pluripotency in xeno-free culture conditions.
Akon Higuchi, Hsing-Fen Li, S. Suresh Kumar, Abdullah A. Alarfaj, Murugan A. Munusamy

Chapter 15. Various Functional and Stimuli-Responsive Hydrogel Based on Polyaspartamides

Polyaspartamides are amide derivatives of biodegradable poly(aspartic acid), the thermal polycondensate of aspartic acid, which have been investigated as carriers for macromolecular prodrugs, platforms for many functional polymers and gels, and macromolecular nano-assemblies for drug delivery system. In this chapter, various different stimuli-responsive (temperature, pH, ion, redox, CO2, etc.), physical and chemical, hydrogel systems based on polyaspartamides will be reviewed with interests for the development of various smart biomaterials and industrial polymeric gels.
Bo Wang, Ji-Heung Kim

Chapter 16. Hydrogels from Catechol-Conjugated Polymeric Materials

Digging into in vivo phenomena is not always a vain task. Its merits will lighten sooner or later. Indeed, in the last two decades, Nature has unveiled to scientists the adhesiveness of proteins secreted within the mussel feet, to a large spectrum of substrata, and, unexpectedly, in aqueous environment. The secret behind this bio-adhesiveness lies on the synergetic adhesive action of 3, 4-dihydroxyphenyl-l-alanine (l-DOPA) and lysine, two amino acid residues in protein skeleton. Mimicking the mussel feet protein (mfp), a plethora of synthetic and natural polymers functionalized with catechol-containing molecules such as l-DOPA were considered as platforms for hydrogel making. Hydrogels tackled in this chapter include those based on poly(alkene oxide)s including poly(ethylene glycol) (PEG) and Pluronics (PEO/PPO/PEO), polyacrylics, alginate, chitosan, gelatin, hyaluronic acid, polypeptides, polyamides, polyesters, polyurethane, poly(vinyl alcohol), and polyallylamine. The applications thereof, in tune with the properties of polymer–catechol conjugates, are propitiously highlighted.
Saad Moulay
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