Immobilization of fluorescein on hemostatic starch particles for tracking degradation and distribution in vivo

Abstract

Starch based particles have been developed as hemostatic products; however, their detailed in vivo degradation and metabolization were rarely reported. This paper aims to develop an absorbable starch-based hemostatic material with optimal hemostatic efficacy and to investigate its degradation and distribution pathways using fluorescein labeling techniques. Starch is etherified to yield carboxymethyl starch (CMS), which is subsequently cross-linked with sodium trimetaphosphate (STMP) to form cross-linked carboxymethyl starch microspheres (CCMS). The water absorption swelling ratio of the cross-linked starch powder can reach 12.44 ± 0.13. The cross-linked starch powder demonstrates superior hemostatic performance and in vitro degradability compared to the commercially available absorbable starch-based hemostatic powder Surgiclean®. Subcutaneous implantation experiments revealed that CCMS implantation induced no chronic inflammation or foreign body reactions (with the absence of fibrous capsule formation), indicating excellent biocompatibility. 5-(4,6-Dichlorotriazinyl) aminofluorescein (5-DTAF) was immobilized on the crosslinked starch powders. The fluorescence-labeled starch hemostatic powders were applied in the abdominal and back wound models to study the metabolism and degradation in vivo. The results showed that the degradation started from 3 days after implantation, and the degraded products were transported via blood, metabolized via kidneys and excreted via urine. After 7 days, the residual amounts of the degraded and metabolized products were very low, and no systemic immune response and wound infection were observed during the in vivo experiments.