Preface

This book discusses hydrogels, presenting pioneering studies on their use in modern "smart" applications, multiutility delivery platforms, 3D and 4D printing, and more.

Hydrogels have demonstrated great impact in many medical and biomedical fields in diagnostics and therapeutics (aesthetic medicine, tissue engineering, drug screening, cancer therapy, etc.). This book highlights the design and engineering of hydrogels for use as efficient drug carriers. It describes stimuli-responsive hydrogels, nanogels, and therapeutic release from 3D printed hydrogels.

The beneficial characteristics of hydrogels are very well known and include biodegradability, biocompatibility, porosity, elasticity, flexibility, and biological properties similar to the extracellular matrix. This book discusses the latest advances in multifunctional hybrid hydrogels with responsiveness to electric and magnetic fields and with applications in biomedicine. In combination with certain nanomaterials, hydrogels are considered a new class of materials that offers new opportunities for living organisms, such as machine interfacing for application biomedical engineering, soft robotics, soft electronics, and environmental and energy science.

Important aspects related to the hydrogel's unique applications in tissue engineering and regenerative medicine are closely related to their self-healing power, interactive structure, low cost, non-toxicity, bio-adhesion, conductivity, elasticity, softness, swelling behavior, transparency, stimuli-responsive ability, and controlled release of various bioactive agents. As presented in the book, hydrogels represent versatile systems with desirable properties, such as viscoelasticity, degradability, biocompatibility, and stimuli-responsiveness, being explored for 4D bioprinting of organs and tissues. However, present outcomes are far from manufacturing an outstanding human-scale tissue construct.

Hydrogels have potential to be combined with mesenchymal stem or stromal cells. These composites could represent valuable alternatives in tissue engineering, as is also discussed in the book.

Three-dimensional hydrogel networks, which tend to imbibe water, have hydrophilic tendency and are excellent super-absorbent materials that still remain water insoluble.

Supramolecular hydrogels could be generated via spontaneous self-assembly with various peptides, proteins, or other biomolecules. These materials have attracted attraction as next-generation drug delivery substitutes to synthetic polymers.

To conclude, hydrogels have proven adaptability and versatility, which makes them particularly interesting for the newest and most modern applications, even artificial intelligence. This book contributes to the understanding of hydrogels and their many beneficial uses.

> **Lăcrămioara Popa, Mihaela Violeta Ghica and Cristina Elena Dinu-Pîrvu** Faculty of Pharmacy, "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania

> > **1**

**Chapter 1**

**1. Introduction**

Introductory Chapter: Hydrogels in

Comprehensive Overviews, Recent

Trends on Their Broad Applications

Initial research of hydrogels started in 1894 when the usage of inorganic salts led to a colloidal gel [1]. Once they come into contact with fluids, hydrogels proceed to incorporate and expand to create a three-dimensional (3D) structure considering the presence of hydrophilic groups (amino, hydroxyl, carboxyl, and amide) in their structure [2]. Bemmelen was the first who established the term "hydrogel" to characterize hydrophilic polymeric systems, with high efficiency to absorb huge amounts of water or other fluids (e.g., biological fluids) in their interstitial networks [3]. The first presence on the market for a 3D network is registered in 1949 when a hydrogel based on poly(vinyl alcohol) was crosslinked with formaldehyde, which was retailed with the name Ivalon, utilized as a biomedical implant [4]. The current definition of hydrogel was established on the groundbreaking work of Lim and Wichterle, who used in 1960 gels based on poly (2-hydroxymethyl methacrylate) to create soft contact lenses. This novelty represented

*Cristina Elena Dinu-Pîrvu and Elena-Emilia Tudoroiu*

the onset of hydrogel investigation for applications in the biological field [1].

The progress of these semisolid systems is characterized by three generations of hydrogels. The first one is represented by chemically crosslinked hydrogels that show excellent swelling and high mechanical stability. The second generation was influenced by Kuhn's research about the configuration of ionizable polymeric particles [5]. The last generation of hydrogels was encouraged by the stimuli-receptivity of the hydrogel second generation. Hence, smart hydrogels are stimuli-responsive with

The water aspect in a hydrogel can establish the general permeation of nutrients into and biological products out of the hydrogel. When a moistureless hydrogel starts to swallow the water, primary particles of water that penetrate the cellular matrix will hydrate the most hydrophilic groups, which conduces to "primary bound water" [7]. Consequently, the polar parts hydrate, the network absorbs the water, and lets out hydrophobic groups that likewise connect with molecules of water; therefore, the water is hydrophobically bound, which means the "secondary bound water" [8]. Primary and secondary bounds of water usually link, and the resulting combination is named

**2. Classification, source, and structure of hydrogels**

adjustable mechanical and physicochemical characteristics [6].

*Lăcrămioara Popa, Mihaela Violeta Ghica,* 
