On-Demand Dissolution of Chemically Cross-Linked Hydrogels

Abstract

Conspectus The formation and subsequent on-demand dissolution of chemically cross-linked hydrogels is of keen interest to chemists, engineers, and clinicians. In this Account, we summarize our recent advances in the area of dissolvable chemically cross-linked hydrogels and provide a comparative discussion of other recent hydrogel systems. Using biocompatible macromonomers, we developed a library of cross-linked dendritic hydrogels that possess favorable properties, including biocompatibility, tissue adhesion, and swelling. Additionally, these hydrogels possess the unique ability to dissolve on-demand via application of a biocompatible aqueous solution. Each of the three hydrogel systems described employs a thiol–thioester exchange reaction as the mechanism of dissolution. These new materials successfully decrease bleeding in in vivo models of hepatic and aortic hemorrhage and dissolve on-demand, providing easy removal. In addition, we evaluated these hydrogels as dressings for second-degree burn wounds and performed proof-of-concept in vivo studies. These hydrogel wound dressings provide a means of repeatedly changing the dressing in a minimally invasive and atraumatic manner while also serving as a protective barrier against bacterial infection. Finally, we highlight the seminal work of other researchers in the field of dissolvable chemically cross-linked hydrogels using thiol–disulfide exchange, retro-Michael-type, and retro-Diels–Alder reactions. These chemistries provide a versatile synthetic toolbox to dissolve hydrogels in a controlled manner on time scales from minutes to weeks. Continued investigation of these dissolution approaches as well as the development of new chemical reactions will open doors to other avenues of on-demand dissolution and expand the application space for these materials. In summary, the management and closure of wounds after traumatic injury or surgical intervention are of significant clinical importance. Stimuli-responsive hydrogels that function as sealants, adhesives, or dressings are emerging as vital alternatives to current standards of care that rely upon conventional sutures, staples, or dressings.

Hydrogels in adipose tissue engineering—Potential application in post‐mastectomy breast regeneration

“…The rate of degradation is determined by the number of enzyme cleavage sites within the hydrogel and the availability of the particular enzyme within the tissue micro‐environment (Drury & Mooney, ). Hydrogel dissolution occurs by several different chemical reactions, which include thiol‐ester exchange, thiol‐disulfide exchange, retro‐Michael‐type addition, and retro‐Diels–Alder reactions (Konieczynska & Grinstaff, ). The by‐products of the biomaterial degradation need to be non‐toxic, cause limited inflammation, and not activate the immune response.…”

The Synthesis of a 2D Ultra‐Large Protein Supramolecular Nanofilm by Chemoselective Thiol–Disulfide Exchange and its Emergent Functions

“…Following a typical nucleophilic substitution mechanism (S N 2 type), thiol–disulfide exchange involves a thiolate attack on one sulfur atom of a disulfide bond, resulting in the breaking of the original disulfide bond with the release of a new thiolate and the formation of a new disulfide bond between the attacking thiolate and another sulfur atom . This reaction contributes a wide range of activities in nature and synthetic systems . Many cellular functions involve this reaction to regulate cell signaling and redox homeostasis by utilizing redox enzymes, namely, thioredoxin (Trx), glutaredoxin (Grx), and peroxiredoxin (Prx), with the assistance of small molecular thiols, such as cysteine (Cys) and glutathione (GSH) .…”

“…Many cellular functions involve this reaction to regulate cell signaling and redox homeostasis by utilizing redox enzymes, namely, thioredoxin (Trx), glutaredoxin (Grx), and peroxiredoxin (Prx), with the assistance of small molecular thiols, such as cysteine (Cys) and glutathione (GSH) . This reaction has also been widely explored in vitro as a versatile tool for the synthesis of functional polymers and materials . In the present work, we propose that the different redox potentials of disulfide bonds among different proteins determine the reactivity of cysteine towards specific proteins (namely, lysozyme) and inertness to other common proteins.…”

Reversible Bioadhesives Using Tannic Acid Primed Thermally‐Responsive Polymers

“…Reversible adhesives reported to date rely on reversible bond formation and cleavage between the adhesive network and the substrate, with the detachment triggered by factors including light, temperature,1a,4 pH, and chemical treatment . Bioinspired adhesives have also been developed that replicate the hierarchical structures of organisms showing reversible adhesions.…”