A Choline Phosphoryl-Conjugated Chitosan/Oxidized Dextran Injectable Self-Healing Hydrogel for Improved Hemostatic Efficacy

Abstract

The development of injectable hydrogels with good biocompatibility, self-healing, and superior hemostatic properties is highly desirable in emergency and clinical applications. Herein, we report an in situ injectable and self-healing hemostatic hydrogel based on choline phosphoryl functionalized chitosan (CS-g-CP) and oxidized dextran (ODex). The CP groups were hypothesized to accelerate hemostasis by facilitating erythrocyte adhesion and aggregation. Our results reveal that the CS-g-CP/ODex hydrogels exhibit enhanced blood clotting and erythrocyte adhesion/aggregation capacities compared to those of the CS/ODex hydrogels. The CS-g-CP50/ODex75 hydrogel presents rapid gelation time, good mechanical strength and tissue adhesiveness, satisfactory bursting pressure, and favorable biocompatibility. The hemostatic ability of the CS-g-CP50/ODex75 hydrogel was significantly improved compared to that of the CS/ODex hydrogel and commercial fibrin sealant in the rat tail amputation and liver/spleen injury models. Our study highlights the positive and synergistic effects of CP groups on hemostasis and strongly supports the CS-g-CP50/ODex75 hydrogel as a promising adhesive for hemorrhage control.

In situ Injectable Tetra‐PEG Hydrogel Bioadhesive for Sutureless Repair of Gastrointestinal Perforation†

“…The burst pressure test was conducted using a homemade experimental setup described previously. [ 49‐51 ] A piece of fresh and cleaned porcine GI tissue was fixed onto the device. A hole of 4 mm in diameter was made with a scalpel and then sealed by Tetra‐PEG hydrogel generated in situ by a dual syringe.…”

Antibacterial, Fatigue-Resistant, and Self-Healing Dressing from Natural-Based Composite Hydrogels for Infected Wound Healing

“…Oxidized dextran is often used to obtain self-healing ability via the Schiff base reaction with dynamic covalent bonds for wound repair. 36,37 On the other hand, owing to insufficient antimicrobial properties of natural-based hydrogels, N-halamine, 38 quaternary ammonium, 39 and phenols 40 have been introduced to settle the bacterial infection, but the synthetic process is complicated and is mainly valid for contact antimicrobial resistance. Despite much progress for naturalbased hydrogel dressings, it remains uncertificated to effectively coordinate the physical, mechanical, biocompatible, antibacterial, and motion-related performance to facilitate infected wound healing.…”

“…Large efforts have thus been made to improve the mechanical properties via chemical cross-linking, physical cross-linking, and mixing with other synthetic/semisynthetic polymers. , Dynamic Schiff base bonds are considered as a desired candidate to improve the mechanical properties of natural-based hydrogels while preserving their recoverability. Oxidized dextran is often used to obtain self-healing ability via the Schiff base reaction with dynamic covalent bonds for wound repair. , On the other hand, owing to insufficient antimicrobial properties of natural-based hydrogels, N-halamine, quaternary ammonium, and phenols have been introduced to settle the bacterial infection, but the synthetic process is complicated and is mainly valid for contact antimicrobial resistance. Despite much progress for natural-based hydrogel dressings, it remains uncertificated to effectively coordinate the physical, mechanical, biocompatible, antibacterial, and motion-related performance to facilitate infected wound healing.…”

Naturally Derived Injectable Dual-Cross-Linked Adhesive Hydrogel for Acute Hemorrhage Control and Wound Healing

“…Uncontrolled hemorrhage caused by severe injuries during surgery procedures and emergencies often leads to a high risk of morbidity, accounting for more than 30% of global trauma-related deaths each year. − Utilizing topical hemostatic agents for quick and effective bleeding control is crucial in improving survival and subsequent wound recovery. − Over the past decades, tremendous research efforts have been made and hemostatic agents come in many flavors, such as gauze/bandage, , granule/powder, − sponge/foam, , hydrogel, − paste, and cryogel, , etc. Among these materials, hydrogel-based bioadhesives that block the bleeding sites through adhesive sealing have risen as promising alternatives or adjuncts to the invasive suturing and stapling techniques for trauma management, owing to their easy-to-use, hydrated three-dimensional (3D) networks and structurally similar to extracellular matrix (ECM), tunable physicochemical properties, and permeability to oxygen and nutrient for wound healing. , In particular, the in situ forming injectable hydrogel adhesives are highly beneficial for conforming and filling the deep, narrow, and irregularly shaped defects in a minimally invasive fashion. − However, the clinically available injectable adhesives (such as fibrin glue, cyanoacrylate, and albumin-glutaraldehyde BioGlues) generally display several limitations, including slow adhesion formation, weak wet adhesion strength, unsatisfied mechanical performance, and even poor biocompatibility and biodegradability, which may result in a substantially compromised hemostatic outcome and delayed wound healing. , Given the magnitude of these problems, developing an injectable hydrogel capable of integrating high mechanical strength, fast tough tissue adhesion, and facilitating tissue repair is highly desirable clinically and remains an ongoing challenge.…”