The main aim of this review is to assess the potential use of natural cross-linking agents, such as genipin, citric acid, tannic acid, epigallocatechin gallate, and vanillin in preparing chemically cross-linked hydrogels for the biomedical, pharmaceutical, and cosmetic industries. Chemical cross-linking is one of the most important methods that is commonly used to form mechanically strong hydrogels based on biopolymers, such as alginates, chitosan, hyaluronic acid, collagen, gelatin, and fibroin. Moreover, the properties of natural cross-linking agents and their advantages and disadvantages are compared relative to their commonly known synthetic cross-linking counterparts. Nowadays, advanced technologies can facilitate the acquisition of high-purity biomaterials from unreacted components with no additional purification steps. However, while planning and designing a chemical process, energy and water consumption should be limited in order to reduce the risks associated with global warming. However, many synthetic cross-linking agents, such as N,N′-methylenebisacrylamide, ethylene glycol dimethacrylate, poly (ethylene glycol) diacrylates, epichlorohydrin, and glutaraldehyde, are harmful to both humans and the environment. One solution to this problem could be the use of bio-cross-linking agents obtained from natural resources, which would eliminate their toxic effects and ensure the safety for humans and the environment.

1. Introduction

Hydrogels constitute hydrophilic three-dimensional networks, which are obtained through the cross-linking reactions of synthetic and/or natural polymers. They are primarily characterised by their ability to absorb water from 10–20% (an arbitrary lower limit) up to thousands of times their dry weight [1,2,3]. Polymers of a natural origin are becoming increasingly used as raw materials to prepare the hydrogels. This is due to their low cost and the lack of a negative impact on the environment, as well as the biofunctionality of the derivative products. The most frequently used groups of natural polymers are polysaccharides, e.g., alginate, chitosan, hyaluronic acid, and proteins (collagen, gelatin, fibrin). Generally, these polymers enable the production of hydrogels that offer desirable properties such as biocompatibility, biodegradability, and non-cytotoxicity. Given their various positive features, hydrogel materials have been widely used in the pharmaceutical and medical industries, e.g., in wound healing dressings, controlled drug or vaccine delivery systems, soft tissue engineering, tissue implants, hygiene products, and in the production of contact lenses