Development of alginate macroporous hydrogels using sacrificial CaCO3 particles for enhanced hemostasis

Abstract

Polymeric hydrogels have increasingly garnered attention in the field of hemostasis. However, there remains a lack of targeted development and evaluation of non-dense polymeric hydrogels with physically incorporated pores to enhance hemostasis. Here, we present a facile route to macroporous alginate hydrogels using acid-induced CaCO3 dissolution to provide Ca2+ for alginate gelation and CO2 bubbles for subsequent macropore formation. The as-prepared pore structure in the hydrogels and its formation mechanisms were characterized through microscopic imaging and nitrogen adsorption/desorption tests. Functional analyses revealed that the macroporous hydrogels exhibited improved rheology, blood absorption, coagulation factor delivery, and platelet aggregation. Ultimately, the introduction of pores significantly enhanced the hemostatic effectiveness of alginate hydrogels in vivo, as demonstrated in rat tail amputation and liver injury models, leading to a reduction in blood loss of up to 77 % or a decrease in bleeding time of up to 88 %. Notably, hydrogels with higher porosity achieved with a CaCO3 to alginate ratio of 40 % outperformed those with lower porosity in the aforementioned properties. Furthermore, these improvements were found to be biocompatible and elicited minimal inflammation. Our findings underscore the potential of a simple porous hydrogel design to enhance hemostasis efficacy by physically incorporating macropores.