Low-Swelling Adhesive Hydrogel with Rapid Hemostasis and Potent Anti-Inflammatory Capability for Full-Thickness Oral Mucosal Defect Repair

Abstract

Full-thickness oral mucosal defects are accompanied by significant blood loss and frequent infections. Instead of conventional therapies that separate hemostasis and anti-inflammation in steps, emerging hydrogels can integrate multiple functions for the successive process after defect including hemostasis/inflammatory phase, proliferative phase, and remodeling phase. However, these functions can be easily compromised by rapid swelling and degradation of hydrogels in wet oral environment. Herein, a low-swelling adhesive hydrogel with rapid hemostasis and potent anti-inflammatory capability was developed using a dual cross-linking strategy as well as a safe and facile fabrication method. It was double cross-linked hydrogel consisting of gelatin methacrylate (GelMA), nanoclay, and tannic acid (TA) (referred to as GNT). GNT hydrogel exhibited low-swelling (one-eighth of that of GelMA), excellent stretchability (211.86%), and good adhesive properties (5 times the adhesive strength of GelMA). Physicochemical characterization illuminated the close interactions among the three components. A systematic investigation of the therapeutic effects of GNT hydrogels was performed. In vitro and in vivo experimental results demonstrated the potent hemostatic property and excellent antibacterial and anti-inflammatory effects of GNT hydrogels. The RNA sequencing analysis results for rat full-thickness oral mucosal samples showed that GNT reduced inflammation levels by down-regulating the expression of multiple inflammation-related pathways, including TNF and IL-17 pathways. It also enhanced the expression levels of tissue regeneration-related genes and thus accelerated defective mucosal repair. More importantly, the therapeutic effects of GNT were superior to those of a commercial oral tissue repair membrane when applied for full-thickness oral mucosal defect repair in rabbits. In summary, the prepared low-swelling adhesive GNT hydrogel with rapid hemostasis and potent anti-inflammatory is a promising therapy for full-thickness mucosal defect in the moist and dynamic oral environment.

Fabrication and Characterization of π–π Stacking Peptide-Contained Double Network Hydrogels

“…The swelling ratios of FFK/PEGDA hydrogels showed the consistence with the degradation ratios and mechanical properties. Therefore, the FFK/PEGDA hydrogels have the excellent potential to be applied in specific moist in vivo environment due to the swelling properties …”

“…Therefore, the FFK/PEGDA hydrogels have the excellent potential to be applied in specific moist in vivo environment due to the swelling properties. 34 3.7. Biocompatibility of FFK/PEGDA Hydrogel.…”

Recent advances in adhesive materials used in the biomedical field: adhesive properties, mechanism, and applications

“…Traditional adhesives are usually based on natural biological components or organic solvents, which can only be used in dry or low-humidity environments. 96 However, adhesives often need to be able to bond effectively in an aqueous environment for tissue adhesion in biomedical applications. However, conventional commercially available polymer adhesives are often weakened or destroyed in an aqueous environment.…”

Advances of Mussel-Inspired Nanocomposite Hydrogels in Biomedical Applications

“…The 1D nanomaterials are nanowires, nanorods, or nanotubes, with a large length-to-diameter ratio, such as carbon nanotubes (CNTs) [ 23 ], gold nanorods (Au NRs) [ 24 ], and cellulose nanofibers (CNFs) [ 25 ]. The 2D nanomaterials are nanosheets with monolayer or multilayer structures and relatively large diameter-to-thickness ratios, such as graphene oxide (GO) [ 26 ], clay [ 27 ], talc, phosphate-based nanosheets, and metal carbides and nitrides [ 28 ]. However, it is generally difficult to achieve a uniform distribution of nanomaterials in hydrogels due to their weak interactions with the polymer chains.…”