Multifunctional two-component in-situ hydrogel for esophageal submucosal dissection for mucosa uplift,postoperative wound closure and rapid healing

Endoscopic submucosal dissection (ESD) for gastrointestinal tumors and premalignant lesions needs submucosal fluid cushion (SFC) for mucosal uplift before dissection, and wound care including wound closure and rapid healing postoperatively. Current SFC materials as well as materials and/or methods for post-ESD wound care have single treatment effect and hold corresponding drawbacks, such as easy dispersion, short duration, weak hemostasis and insufficient repair function. Thus, designing materials that can serve as both SFC materials and wound care is highly desired, and remains a challenge. Herein, we report a two-component in-situ hydrogel prepared from maleimide-based oxidized sodium alginate and sulfhydryl carboxymethyl-chitosan, which gelated mainly based on "click" chemistry and Schiff base reaction. The hydrogels showed short gelation time, outstanding tissue adhesion, favorable hemostatic properties, and good biocompatibility. A rat subcutaneous ultrasound model confirmed the ability of suitable mucosal uplift height and durable maintenance time of AM solution. The in vivo/in vitro rabbit liver hemorrhage model demonstrated the effects of hydrogel in rapid hemostasis and prevention of delayed bleeding. The canine esophageal ESD model corroborated that the in-situ hydrogel provided good mucosal uplift and wound closure effects, and significantly accelerated wound healing with accelerating re-epithelization and ECM remodeling post-ESD. The two-component in-situ hydrogels exhibited great potential in gastrointestinal tract ESD.

A self-fused hydrogel for the treatment of glottic insufficiency through outstanding durability,extracellular matrix-inducing bioactivity and function preservation

Injection laryngoplasty with biomaterials is an effective technique to treat glottic insufficiency.However,the inadequate durability,deficient pro-secretion of extracellular matrix(ECM)and poor functional preservation of current biomaterials have yielded an unsatisfactory therapeutic effect.Herein,a self-fusing bioactive hydrogel comprising modified carboxymethyl chitosan and sodium alginate is developed through a dual-crosslinking mechanism(photo-triggered and dynamic covalent bonds).Owing to its characteristic networks,the synergistic effect of the hydrogel for vocal folds(VFs)vibration and phonation is adequately demonstrated.Notably,owing to its inherent bioactivity of polysaccharides,the hydrogel could significantly enhance the secretion of major components(type I/III collagen and elastin)in the lamina propria of the VFs both in vivo and in vitro.In a rabbit model for glottic insufficiency,the optimized hydrogel(C1A1)has demonstrated a durability far superior to that of the commercially made hyaluronic acid(HA)Gel.More importantly,owing to the ECM-inducing bioactivity,the physiological functions of the VFs treated with the C1A1 hydrogel also outperformed that of the HA Gel,and were similar to those of the normal VFs.Taken together,through a simple-yet-effective strategy,the novel hydrogel has demonstrated outstanding durability,ECM-inducing bioactivity and physiological function preservation,therefore has an appealing clinical value for treating glottic insufficiency.

Multi-crosslinking hydrogels with robust bio-adhesion and pro-coagulant activity for first-aid hemostasis and infected wound healing

Bio-adhesive polysaccharide-based hydrogels have attracted much attention in first-aid hemostasis and wound healing for excellent biocompatibility,antibacterial property and pro-healing bioactivity.Yet,the inadequate mechanical properties and bio-adhesion limit their applications.Herein,based on dynamic covalent bonds,photo-triggered covalent bonds and hydrogen bonds,multifunctional bio-adhesive hydrogels comprising modified carboxymethyl chitosan,modified sodium alginate and tannic acid are developed.Multi-crosslinking strategy endows hydrogels with improved strength and flexibility simultaneously.Owing to cohesion enhancement strategy and self-healing ability,considerable bio-adhesion is presented by the hydrogel with a maximal adhesion strength of 162.6 kPa,12.3-fold that of commercial fibrin glue.Based on bio-adhesion and pro-coagulant activity(e.g.,the stimulative aggregation and adhesion of erythrocytes and platelets),the hydrogel reveals superior hemostatic performance in rabbit liver injury model with blood loss of 0.32 g,only 54.2%of that in fibrin glue.The healing efficiency of hydrogel for infected wounds is markedly better than commercial EGF Gel and Ag+Gel due to the enhanced antibacterial and antioxidant properties.Through the multi-crosslinking strategy,the hydrogels show enhanced mechanical properties,fabulous bio-adhesion,superior hemostatic performance and promoting healing ability,thereby have an appealing application value for the first-aid hemostasis and infected wound healing.