Facile preparation of injectable, thermosensitive, and physically cross-linked hemostatic hydrogel with rapid gelation and a robust network

Abstract

Biomimetic and thermoresponsive hemostatic hydrogels based on gelatin (G), hyaluronic acid (HA), and poly-N-isopropylacrylamide (PNIPAM) have emerged as promising hemostats, but their performances are currently limited by the drawbacks of conventional grafting strategies, and the complicated operation and safety risk associated with photo-cross-linking or chemical cross-linking. It is highly appealing yet challenging to develop a facile strategy to prepare a physically cross-linked hemostatic hydrogel with rapid gelation and a robust network. Herein, an injectable, thermosensitive, and physically cross-linked double-network hemostatic hydrogel was prepared through simply blending G/HA with the linear PNIPAM (L-P) synthesized by reversible addition–fragmentation chain transfer (RAFT) polymerization. The G/HA/L-P hydrogel could be conveniently injected via a syringe and cured in situ at body temperature. Its comprehensive performance could be tuned and optimized by adjusting the molecular weight of L-P and the proportions of components. Due to the non-covalent interactions including hydrogen bonding, hydrophobic interactions, and chain entanglements within the hydrogel network, the optimal performance of the G/HA/L-P hydrogel was achieved, i.e., gelation time 7–10 s, storage modulus 89 ± 3.5 kPa, adhesion strength 19.3 ± 2.5 kPa, and burst pressure 256 ± 27 mmHg. Meanwhile, the hydrogel exhibited significant coagulation effects in vitro and effective hemostatic properties in vivo. This work offers a simple and efficient strategy to fabricate high-performance smart hemostatic hydrogels.