Hydrogel – Is it a Biomaterial?

Introduction

Hydrogels, composed of natural or synthetic polymers, have gained attention for cell encapsulation and tissue engineering. They can absorb large amounts of water, from 10-20% to thousands of times their dry weight. Hydrogels vary in stability, some degrading over time. Reversible or physical hydrogels are formed through molecular entanglements and secondary forces like ionic, hydrogen bonding, or hydrophobic interactions. These physical hydrogels have inhomogeneities due to molecular clusters and transient network defects caused by free chain ends or loops.

Figure -1 Schematic of methods for formation of two types of ionic hydrogels. An example of an ‘ionotropic’ hydrogel is calcium alginate, and an example of a polyionic hydrogel is a complex of alginic acid and polylysine [2].

Hydrogel Structure

Hydrogels can be permanent or chemical gels when their networks are held together by covalent bonds. Synthetic hydrogels, like those created by Wichterle and Lim, use a process called copolymerization with a substance called ethylene glycol dimethacrylat (EGDMA). These chemical gels can also form through crosslinking water-soluble polymers or changing hydrophobic polymers into hydrophilic ones and forming a network. Sometimes, crosslinking is not needed. For instance, in the hydrolysis of polyacrylonitrile (PAN), if the nitrile groups stay close together, they can make a hydrogel through hydrophobic interactions. In their crosslinked form, chemical hydrogels swell in water to a level depending on the crosslink density, which is related to the distance between crosslinks. Just like physical hydrogels, chemical hydrogels are not uniform; they have areas with low water swelling and high crosslink density called “clusters” among areas with high swelling and low crosslink density. This could be due to crosslinking agents sticking together in some parts. Sometimes, when making chemical gels, the solvent, temperature, and concentration of solids can cause separation, creating water-filled spaces called “voids” or “macropores.” In these chemical gels, defects like free chain ends, chain loops, and entanglements exist but don’t contribute to the permanent network’s elasticity.

Figure-2 Schematic of methods for formation of hydrogels by chemical modification of hydrophobic polymers [2].

Properties of Hydrogel

There are various possible structures for both physical and chemical hydrogels, each with different macromolecular arrangements. These include networks of crosslinked or entangled linear homopolymers, linear copolymers, and block or graft copolymers. Additionally, hydrogels can involve complexes like polyion-multivalent ion, polyion-polyion, or hydrogen-bonded structures. They can also be hydrophilic networks with hydrophobic areas for stability, or they might be interpenetrating networks (IPNs) or physical blends. Hydrogels can take on different physical forms as well. For example, they can be molded into solid shapes like soft contact lenses, used as pressed powder matrices such as pills or capsules for oral ingestion, turned into microparticles for uses like wound treatments, applied as coatings on implants or catheters, transformed into membranes or sheets for drug delivery patches, encapsulated as solids in devices like osmotic pumps, or even exist as liquids that turn into gels when heated or cooled.

Figure-3 Schematic of methods for formation of crosslinked hydrogels by free radical reactions, including a variety of polymerizations and crosslinking of water-soluble polymers. Examples include crosslinked PHEMA and PEG hydrogels [2].

Future Perspectives

Hydrogels have gained prominence as promising candidates for tissue engineering applications. They can be engineered to accommodate living cells through the creation of pores or controlled degradation, facilitating cell penetration and growth. One advantage of hydrogels in tissue engineering is their ability to incorporate cell membrane receptor peptide ligands, enhancing cell adhesion and growth. However, a notable drawback is their limited mechanical strength, making handling a challenge. Sterilization also poses difficulties. While hydrogels offer significant potential, it’s clear that addressing these limitations is essential for their successful utilization in tissue engineering.

Reference

[1] https://www.medicalnewstoday.com/articles/hydrogel-patches-could-prevent-melanoma-breast-cancer-and-colon-cancer-from-recurring#Challenges-lie-ahead

[2] Hoffman, A.S., 2012. Hydrogels for biomedical applications. Advanced drug delivery reviews, 64, pp.18-23.