Recent advances of on-demand dissolution of hydrogel dressings

Abstract

Wound management is a major global challenge and a big financial burden to the healthcare system due to the rapid growth of chronic diseases including the diabetes, obesity, and aging population. Modern solutions to wound management include hydrogels that dissolve on demand, and the development of such hydrogels is of keen research interest. The formation and subsequent on-demand dissolution of hydrogels is of keen interest to scientists and clinicians. These hydrogels have excellent properties such as tissue adhesion, swelling, and water absorption. In addition, these hydrogels have a distinctive capacity to form in situ and dissolve on-demand via physical or chemical reactions. Some of these hydrogels have been successfully used as a dressing to reduce bleeding in hepatic and aortal models, and the hydrogels remove easily afterwards. However, there is an extremely wide array of different ways to synthesize these hydrogels. Therefore, we summarize here the recent advances of hydrogels that dissolve on demand, covering both chemical cross-linking cases and physical cross-linking cases. We believe that continuous exploration of dissolution strategies will uncover new mechanisms of dissolution and extend the range of applications for hydrogel dressings.

Keywords: Hydrogel; On-demand dissolution; Wound dressing; Wound management.

Fig. 1

Schematic illustration of hydrogels fabricated through chemically cross-linked or physically cross-linked

Fig. 2

Formation of poly(ethylene glycol) lysine sulfhydryl (PEG-lysSH) and subsequent dissolution. a Thiol-thioester exchange reaction [37]. b The example of a hydrophilic PEG-lysSH hydrogel dissolution based on thiol-thioester exchange. Figures are adapted with permission from the original articles of Ghobril et al. [37] (Copyright 2013 by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim). CME cysteine methyl eater

Fig. 3

Thiol-disulfide exchange reaction based hydrogels formation and theirs dissolution. a Thiol-disulfide exchange reaction. Figure is adapted with permission from the original articles of Houk and Whitesides [43] (Copyright 1987 by Amerian Chemical Society). b Reaction scheme for hydrogel preparation and its reliquefaction. Figure is adapted with permission from the original articles of Hisano et al. [45] (Copyright 1988 by John Wiley & Sons, Inc.). c Schematic representation of thiopyridyl terminations appended on the 8-arm-poly(ethylene glycol) (PEG)-SH to form 8-arm-PEG-S-TP. Thiopyridine is a good leaving group and the 8-arm-PEG-S-TP forms disulfide bridges with the 8-arm-PEG-SH in phosphate buffer (PB) (pH 8) resulting in S-TP hydrogels [47]. d Schematic of the reversible nature of hydrogels. Glutathione (GSH) acts as a thiolate moiety and attacks the disulfide bonds resulting in the breakdown of the hydrogel network (gel to sol transition). The possible products are 8-arm-PEG-SH, 8-arm-PEG-(SH)-S-SG, 8-arm-PEG-S-SG and GS-SG. Figures are adapted with permission from the original articles of Anumolu et al. [47].(Copyright 2010 by Elsevier Ltd.)

Fig. 4

Formation and dissolution of hydrogel based on retro-Michael addition reaction. a Michael addition and retro-Michael reaction. Figure is adapted with permission from the original articles of Konieczynska and Grinstaff [36] (Copyright 2017 by American Chemical Society). b Hydrogel formation using maleimide-functionalized low-molecular weight heparin (MAL-LMWH) and poly(ethylene glycol) (PEG)-thiols; degradation mechanisms for ester and succinimide thioether groups. Figure is adapted with permission from the original articles of Baldwin and Kiick [48] (Copyright 2013 by Royal Society of Chemistry). GSH glutathione, PBS phosphate buffer saline

Fig. 5

Retro-Diels-Alder reaction based hydrogels formation and their dissolution. a Michael addition and Diels-Alder (DA) reaction. Figure is adapted with permission from the original articles of Koehler et al. [51] (Copyright 2013 by American Chemical Society). b Formation and degradation of poly(ethylene glycaol)-oxanorbornadiene (PEG-OND) hydrogels. Figure is adapted with permission from the original articles of Higginson et al. [53] (Copyright 2015 by American Chemical Society). c The DA reaction was investigated as a cross-linking mechanism for PEG-based hydrogels. Figure is adapted with permission from the original articles of Kirchhof et al. [54] (Copyright 2013 by Royal Society of Chemistry)

Fig. 6

Schematic illustration of the dissolution or swelling behavior of stimuli sensitive physically cross-linked hydrogels

Fig. 7

Schematic depiction of a supramolecular hydrogel fabrication from supramonomers and its dissolution process upon memantine irrigation [96] and b its application as wound dressing materials. Figures are adapted with permission from the original articles of Xu et al. [96] (Copyright 2017 by American Chemical Society). CB cucurbit, FGG-EA Phe-Gly-Gly ester derivative