Marine-inspired molecular mimicry generates a drug-free, but immunogenic hydrogel adhesive protecting surgical anastomosis

Abstract

Herein, we report the synthesis of a biomimic hydrogel adhesive that addresses the poor healing of surgical anastomosis. Dopamine-conjugated xanthan gum (Da-g-Xan) is fabricated using deep insights into the molecular similarity between mussels' adhesive and dopamine as well as the structural similarity between barnacle cement proteins and xanthan gum. The hydrogel mimics marine animals’ adherence to wet tissue surfaces. Upon applying this adhesive to colonic anastomosis in a rat model, protective effects were shown by significantly improving the bursting pressure. Mechanistically, the architecture of Da-g-Xan hydrogel is maintained by dynamic intermolecular hydrogen bonds that allow the quick release of Da-g-Xan. The free Da-g-Xan can regulate the inflammatory status and induce type 2 macrophage polarization (M2) by specifically interacting with mannose receptors (CD206) revealed by RNA-sequencing and molecular binding assays. Consequently, an appropriate microenvironment for tissue healing is created by the secretion of chemokines and growth factors from M2 macrophages, strengthening the fibroblast migration and proliferation, collagen synthesis and epithelial vascularization. Overall, this study demonstrates an unprecedented strategy for generating an adhesive by synergistic mimicry inspired by two marine animals, and the results show that the Da-g-Xan adhesive augments native tissue regenerative responses, thus enabling enhanced recovery following surgical anastomosis.

Mussel-Inspired Catechol Functionalisation as a Strategy to Enhance Biomaterial Adhesion: A Systematic Review

“…Aiming at addressing the poor healing of postoperative anastomotic leakage (PAL), a severe complication of gastrointestinal surgery, Huang et al [ 41 ] developed a novel hydrogel formulation composed of xanthan gum (Xan) modified with DA via EDC/NHS coupling (DS = 4% to 16%), to obtain a functionalised Xan hydrogel (DA-g-Xan) with improved adhesive properties. The combination of moderately adhesive Xan with DA was found to be sufficient for the induction of hydrogel crosslinking, due to the abundant intermolecular hydrogen bond interactions.…”

Review of Colonic Anastomotic Leakage and Prevention Methods

“…Preoperative and intraoperative therapies such as Figure 6. Background on the marine-inspired immunogenic hydrogel adhesive [100], reprinted with permission from science direct under CC BY-NC-ND 4.0.…”

“…The hydrogel adheres to wet tissue surfaces, like that of marine animals, thus improving bursting pressure. Additionally, intermolecular bonds allow the quick release of Da-g-Xan which can regulate inflammatory status and induce type 2 macrophage polarization [ 100 ]. However, this technique has only been tested on rats.…”

Application of Nanomaterial in Hydrogels Related to Wound Healing

“…Improving Mechanical Performance. Hydrogel is a threedimensional hydrophilic network, insoluble in water or aqueous solutions, and capable of absorbing water or other biological fluids [25,26]. It can promote the healing process, rehydrate necrotic tissue and increase the healing of debridement, and cool the wound surface, and it is suitable for cleaning dry, loose, or necrotic wounds [21,27].…”