Design and Synthesys of Highly Stretchable and Tough Adhesive Hydrogels for Dry and Wet Biomedical Applications

Review Article

Austin Chem Eng. 2022; 9(1): 1089.

Design and Synthesys of Highly Stretchable and Tough Adhesive Hydrogels for Dry and Wet Biomedical Applications

Neves D, Oechsler BF and Machado RAF*

Chemical Engineering Program, Federal University of Santa Catarina, Florianopolis, Santa Catarina State, Brazil

*Corresponding author: Ricardo AF Machado, Chemical Engineering Program, Federal University of Santa Catarina, PO Box 476, Zip Code 88040900, Florianopolis, Santa Catarina State, Brazil

Received: March 22, 2022; Accepted: April 26, 2022; Published: May 03, 2022


The development of less invasive procedures and devices in the biomedical applications of wound closure and healing is an important and essential task. The healing process is facilitated by proper closure of the surgical wound; traditionally a particularly invasive practice. Tissue adhesives design should incorporate simplicity, safety, and painless removal from the skin. Moreover, these materials should have adequate adhesive strength, be tough enough to incorporate the mechanical skin behaviors, and must also show compatibility with body fluids as well as cells and tissues. The design of tough adhesives (TAs) can potentially enable many applications, including the gluing of tissues and attaching devices in vivo, tissue repair, and can be used as a hemostatic dressing because of their compatibility with blood exposure. This work reviews many strategies to design tough hydrogels with the introduction of non-covalent bonds and the construction of stretchable polymer networks and interpenetrated networks, such as a double-network hydrogel. To overcome such difficulties, some synthetic wet adhesives emulating natural adhesive materials of marine organisms have been investigated.

Keywords: Tough Adhesive Hydrogels; Highly Stretchable Adhesives; Dry and Wet Biomedical Applications


Tissue adhesives are used as an alternative to stitches or staples and can be less damaging to the healthy tissues, for example in sutureless in wound closure and wound dressings [1,2]. However, these materials can suffer from low biocompatibility and poor matching of the mechanical properties with the tissues. Therefore, compatibility with body fluids, cells, and tissues is a desirable property [3]. This family of adhesives may be useful in several biomedical applications, including tissue adhesives, wound dressings, and tissue repair.

Adhesion to wet surfaces, including biological tissues, is important in many fields but it has proven to be extremely challenging. Existing adhesives are cytotoxic, adhere weakly to tissues, or cannot be used in wet environments. Firstly the adhesive should form a strong bond with the substrate and, second, the material inside either the adhesive or the substrate should dissipate energy by hysteresis [4].

Commercial strong cyanoacrylate adhesives are incompatible with wet surfaces as they solidify immediately in contact with water, forming a rigid structure that cannot be flexible to the tissue movements, and they exhibit cellular toxicity [5,6]. Biohybrid polymers can be an advanced way that combines properties of adhesiveness, biodegradability, absorbency, and stretching force [7]. Hydrogels have immense potential as reversible wet adhesives when they are integrated with biomimetic microstructures, in which some factors can be considered. Firstly, the hydrophilic nature of the hydrogels is beneficial to induce strong capillary adhesion under wet conditions. Second, they can absorb a large quantity of water at the contact interface, which would allow closer contact with the target substrate [8,9].

While several promising properties and multiple functionalities, such as biocompatibility and environmental friendliness, responsiveness to external stimuli, adhesion, anti-biofouling behavior, and biodegradability have been integrated into hydrogels, the relatively poor mechanical behavior of hydrogels remains a challenge, impeding their use in real-world applications that require mechanical integrity. Particularly, they can be designed to achieve better physical, chemical, electrical and biological properties [10,11]. Furthermore, they are biocompatible and therefore can be used for diverse biomedical applications such as tissue adhesives, tissue repair, scaffolds for cell growth, and wound dressings. Indeed, in recent years, hydrogels have been actively explored as materials for efficient wet adhesives [3,12].

Hydrogels with a single component have a poor mechanical property [13], however, several recent reports related below have shown an improvement in the toughness from the selection of hybrid or composite hydrogels with non-covalent bonds (e.g., hydrogen bonds and ionic interactions), highly stretchable networks and double-network.

In 2003, Gong et al. [11] discovered a double-network highly stretchable hydrogel, and San et al. [14] synthesized a highly stretchable and tough hydrogel, prepared from a network of polyacrylamide and alginate. Ballance et al. [15] demonstrated that linking cyclodextrin chemically in a stretchable polyacrylamide hydrogel increases mechanical strength. Stretching these hydrogels loaded with quinine significantly enhanced the antibacterial activity of the gels due to the increased amount and release rate of quinine, demonstrating antibacterial behavior.

Tough Hydrogels - Dissipative Matrices

Hydrogels are materials that consist of crosslinked polymer networks dispersed in water [16]. Most common hydrogels used for wound dressings or drug delivery systems are brittle, not exhibiting high stretching resistance due to their mechanical behavior. In recent years, intense efforts have been directed toward designing synthetic hydrogels possessing high strength and toughness by engineering energy- dissipative pathways into the gel structure [17,18].

In order to expand the scope of functional hydrogel materials, there is a need to develop new mechanically strong and tough supramolecular hydrogels that could not only be easily accessed from simple and commercially available starting materials, but that also exhibit a combination of desired mechanical properties such as high strength, stretchability, self-recovery, self-healing, fatigue-resistance, and thermoplasticity [19].

Hydrogels with a double or more network of two or more polymer chains, crosslinked separately, in which one of them having short chains and the other having long chains can enable mechanisms to dissipate energy and became tougher [14,20-22].

These double network hydrogels have been demonstrated synergistically combine the stiffness of a tightly cross-linked network with the dissipative ability of an independently formed, loosely crosslinked network. However, the exceptional toughness of a double network gel compromises the material’s fatigue resistance when stretched, as it depends entirely upon the permanent rupture of the short-chain as an energy dissipation mechanism, while the long chains assist in broadening the fracture zone to maximize dissipation. Once the first network has been damaged, the mechanical response is dominated by the much softer second network, and the high stiffness and toughness are lost [14,20]. One way to replace this situation for recoverable energy dissipation is to change the covalent bonds to noncovalent bonds [20].

Li et al. [4] created a bioinspired design for an adhesive consisting of two layers: an adhesive surface with a flexible dissipative matrix, inspired by defensive mucus secreted by slugs that strongly adheres to wet surfaces. The adhesive layer adheres to the substrate by electrostatic interactions, covalent bonds, and physical interpenetration. The second layer is composed of a matrix of hydrogel that can amplify energy dissipation through hysteresis. The two layers lead to higher adhesion energies on wet surfaces when compared with existing adhesives. This bioinspired adhesive has an ideal level of the stick and moves along with the living tissue.

Sun et al. [14] developed the first highly stretchable and tough hydrogels with better deformation and energy dissipation with enhanced mechanical properties, mixing two types of crosslinked polymers: ionic crosslink alginate and a covalently cross-linked polyacrylamide. Alginates chains consist of mannuronic acids (M block) and guluronic acids (G blocks), isolated in their chains or alternated blocks. In water solution, the G blocks on different chains form ionic crosslinks through divalent cations (Ca2+), resulting in a network in water, an alginate hydrogel. The polyacrylamide chains in hydrogel form a network by covalent crosslinks (Figure 1).