Blood loss in traumatic injuries is a critical threat, necessitating the development of hemostatic technologies and biomaterials that suit a diverse range of emergency scenarios for both civilian and military settings. There is an increasing interest in the development of absorbable hemostatic dressings that can be left in the injury site and degrade, eliminating the necessity for later carrier removal, and that reduce the duration of interventional procedures. In the current study, a macrocyclic oligosaccharide, β-cyclodextrin, was allowed to undergo reaction with dianhydride linkers to form hydrogels with large void spaces within the resulting hyperbranched cyclodextrin-based polyester (CDPE) framework. The hydrogel served as a sacrificial macroporous carrier, capable of degradation under physiological conditions, as demonstrated by its gradual hydrolysis into water-soluble, small molecule byproducts over the course of 2 d, when placed in phosphate-buffered saline at 37 °C, as monitored by 1H NMR spectroscopy. The CDPE template enabled the assembly of honeycomb-like monolithic mats of chitosan, containing highly entangled nanofibers with diameters of ca. 9.2 ± 3.7 nm, as measured by scanning electron microscopy, thereby achieving a desired increase in the surface area of chitosan to improve hemostatic efficiency. In vivo, chitosan-loaded cyclodextrin (CDPE-Cs) hydrogels resulted in significantly lower amounts of blood loss and shorter times to hemostasis as compared to Surgicel® and Curaspon®, commercially available absorbable hemostatic dressings, in acute liver punch models of rats, rabbits and pigs. CDPE-Cs hydrogels also exhibited rapid in vivo degradation within 7 d, and high biocompatibility, as demonstrated by histopathological examination of the surrounding liver tissues. The designed absorbable hemostatic hydrogels demonstrated auspicious in vivo hemostatic efficiency, signifying their potential as a physiologically benign approach to mitigating blood loss in tissue-injury scenarios.

Absorbable hemostatic hydrogels comprising sacrificial templates for the assembly of honeycomb-like nanofibrous mats of chitosan

2019 Spring National Meeting

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