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.