Thermoresponsive shear-thinning hydrogel (T-STH) hemostats for minimally invasive treatment of external hemorrhages

Abstract

Hemorrhage is the leading cause of death following battlefield injuries. Although several hemostats are commercially available, they do not meet all the necessary requirements to stop bleeding in combat injuries....

Biomimetic and Multifunctional Hemostatic Hydrogel with Rapid Thermoresponsive Gelation and Robust Wet Adhesion for Emergency Hemostasis: A Rational Design Based on Photo-Cross-Linking Coordinated Hydrophilic–Hydrophobic Balance Strategies

“…19 The thermoresponsive sol−gel phase transition of hemostatic hydrogel is very important for its in situ use in emergency hemostasis. 21,34 Figure 1b shows that the prepared hydrogel sample was in the sol state and could flow at room temperature. As the temperature was increased to 32 °C, the hydrogel transformed into a white and opaque solid.…”

“…In recent years, tremendous efforts have been devoted to the development of novel hemostatic adhesives, and polymeric hydrogels have emerged as promising hemostats to stop bleeding and promote wound healing due to their excellent structural and mechanical similarity to the extracellular matrix (ECM) of biological tissues . Despite a variety of hemostatic hydrogels engineered from natural ,,− and synthetic , polymers, very few of them can be used as first-aid supplies to treat the life-threatening hemorrhage in emergency situations, and achieving robust adhesion under wet and dynamic conditions remains a big challenge. ,, Therefore, advanced hydrogel-based hemostatic materials and strategies that can meet the requirements for emergency hemostasis are urgently needed.…”

“…Although numerous strategies have been proposed to construct different hemostatic hydrogels, such as superwetting, biomimetics, ,− double-network, , chemical cross-linking, , photo-cross-linking, ,,,,,, oxidative cross-linking, − and thermoresponsive design, ,, the ideal hemostat that satisfies all the above requirements for emergency hemostasis is still lacking, and the intrinsic limitations of the current state-of-the-art hemostatic hydrogel systems need to be further addressed. For example, a recent work engineered a promising thermoresponsive hemostatic hydrogel composed of poly- N -isopropylacrylamide (PNIPAM) and silicate nanodisks, which could be used as a first aid hemostat to treat external hemorrhages in emergency situations just via simple injection; however, the antibacterial and wound healing capacities of the hemostat have not been investigated, which are all crucial properties for noncompressible hemorrhage control. Thus, it is highly appealing yet challenging to simultaneously integrate all of the desired characteristics into one hemostatic hydrogel for emergency hemostasis.…”

“…These outstanding properties were mainly attributed to its two internal covalently cross-linked networks, particularly the Schiff base cross-linking network derived from the well-established UV phototriggered imine cross-linking (PIC) reaction. Although the PIC reaction is powerful in enhancing the tissue adhesion and internal strength of hydrogels with no need of a toxic photoinitiator, its direct use for in situ emergency hemostasis might not be feasible owing to the potential issues of UV irradiation such as safety risk, limited penetration, and complicated operations, especially for deep and irregularly shaped wounds. ,, Compared with the chemically or light-induced curing methods of injectable hemostatic hydrogels, the in situ gelation triggered by physiological temperature is more convenient and fascinating, and this strategy has been highly recommended for use in minimally invasive treatments including emergency hemostasis, , while it has been rarely applied to HA/G hydrogels. Due to the characteristic lower critical solution temperature (LCST) of about 32 °C, PNIPAM-based polymers can be soluble and injectable at room temperature and become insoluble and solidified at body temperature, exhibiting thermoresponsive sol–gel phase transition .…”

“…An ideal hemostatic hydrogel for prehospital hemorrhage control in emergency situations should possess the following characteristics: − ,,, (i) rapid in situ gelation, strong wet adhesion, excellent mechanical strength, and suitable swelling properties to quickly stop bleeding and withstand biological pressures (e.g., blood pressure and tissue compression); (ii) efficient antibacterial and wound healing capabilities to inhibit wound infection and promote tissue regeneration; (iii) good biocompatibility and biodegradability with no inflammatory or toxic side-effects; (iv) being injectable to flexibly fill irregularly shaped wounds, ready to use (e.g., prepackaged in a syringe, with no requirement for mixing or further preparation), and simple to use by wounded soldiers and nontrained civilians. Although numerous strategies have been proposed to construct different hemostatic hydrogels, such as superwetting, biomimetics, ,− double-network, , chemical cross-linking, , photo-cross-linking, ,,,,,, oxidative cross-linking, − and thermoresponsive design, ,, the ideal hemostat that satisfies all the above requirements for emergency hemostasis is still lacking, and the intrinsic limitations of the current state-of-the-art hemostatic hydrogel systems need to be further addressed. For example, a recent work engineered a promising thermoresponsive hemostatic hydrogel composed of poly- N -isopropylacrylamide (PNIPAM) and silicate nanodisks, which could be used as a first aid hemostat to treat external hemorrhages in emergency situations just via simple injection; however, the antibacterial and wound healing capacities of the hemostat have not been investigated, which are all crucial properties for noncompressible hemorrhage control.…”