Injectable Hemostat Composed of a Polyphosphate-Conjugated Hyaluronan Hydrogel

Biomacromolecules. 2018 Aug 13;19(8):3280-3290. doi: 10.1021/acs.biomac.8b00588. Epub 2018 Jul 23.

Abstract

We have developed a new hydrogel hemostat composed of hyaluronan (HA) conjugated with inorganic polyphosphate (PolyP). A hemostatic hydrogel, HAX-PolyP, was formed rapidly by mixing aldehyde-modified HA and hydrazide-modified HA conjugated with PolyP (HA-PolyP). Although the gelation rate decreased with increasing PolyP content, the gelation time was below 5 min. In addition, the hydrogel swelling volume decreased with increasing PolyP content, but the degradation rate did not depend on PolyP content and the hydrogel underwent complete degradation through hydrolysis over 3 weeks in phosphate buffered saline. HAX-PolyP showed similar biocompatibility with the HA hydrogel without PolyP conjugation in vitro and in vivo. Intraperitoneal administration of HAX-PolyP did not induce any adhesion in the peritoneum and clot formation in the lungs. Finally, HA-PolyP accelerated the coagulation rate of human plasma ex vivo, and HAX-PolyP showed as strong a hemostatic effect as fibrin glue in a mouse liver bleeding model in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Animals
  • Hemostatics / administration & dosage
  • Hemostatics / chemistry*
  • Humans
  • Hyaluronic Acid / chemistry*
  • Hydrogels / chemistry*
  • Injections
  • Male
  • Mice
  • Mice, Inbred ICR
  • Polyphosphates / chemistry*
  • RAW 264.7 Cells

Substances

  • Hemostatics
  • Hydrogels
  • Polyphosphates
  • Hyaluronic Acid