Injectable hydrogel based on short-peptide RG5 combined with halloysite nanotubes for rapid hemostasis

Rapid and effective hemostasis and high infection rates in trauma care of emergency patients are still a challenge. Herein, we demonstrated a physical–chemical interaction strategy of alginate, gelatin, and hemostatic powder that can produce an injectable hydrogel. RG5 as a hemostatic short peptide was introduced to the lumen of halloysite nanotubes (HNTs), a novel hemostatic powder was prepared by HNTs loading of RG5 with freeze vacuum drying. The morphology of the powder had shown that the internal surface of the hemostatic powder became indistinct and rough observed by transmission electron microscopy (TEM). This result should be attributed to the filling of the peptide RG5 into the lumen of the HNTs. The whole-blood clotting time was observed in vitro that with an increase of the doses of HNTs and hemostatic powder from 15 to 35 mg, the clotting time was a gradually decrease (p < 0.01), while the clotting time of HNTs loading RG5 is the shorter than that of HNTs. The hydrogel was characterized by SEM, FTIR, and rheological analysis in vitro. There was no crossover point where G′ becomes larger than G′′, the rheological behavior result illustrated the AGHR hydrogel remains injectable in extremely hot and cold regions, and was suitable for many types of first aid and battlefield rescue. The in vivo application potential of AGHR hydrogel was evaluated using a liver bleeding model. The hemostatic activity of AGHR hydrogel was comparable with that of commercial hemostatic material such as Celox. In conclusion, the HNTs/RG5 and AGHR hydrogel obtained in this work were biocompatible and hemostatic, and will be a promising hemostatic drug for clinical application. A novel hemostatic powder HNTs/RG5 was developed by introducing short-peptide RG5 to the lumen of halloysite nanotubes (HNTs) with freeze vacuum drying. Herein, we demonstrated a physical–chemical interaction strategy to produce an injectable hydrogel (named as AGHR, corresponding to the initial letter of each raw materials such as alginate, gelatin, and HNTs/RG5 hemostatic powder). The obtained AGHR hydrogels have excellent biocompatibility and rapid hemostatic properties in vivo.