Development of novel aspartic acid-based calcium bio-MOF designed for the management of severe bleeding

Haemostatic agents must play a key role in managing severe bleeding conditions during trauma or battlefield. Using natural ligands and bioactive metals, we can design materials that can enhance innate haemostatic capability. This study entails the synthesis of amino acid-based MOF using l-aspartic acid as an organic ligand and calcium as a metal node, where the parametric optimization is made using a Box-Behnken experimental design. Out of the total experimental runs obtained, the one with the highest reaction yield was evaluated. It was observed that despite low porosity and surface area, the impact of the synthesised Ca-MOF on the haemostatic property was very high. A haemolysis ratio <1.55%, which induces erythrocyte absorption and aggregation, activated the intrinsic coagulation pathway and accelerated blood coagulation as assessed using TEG. The evaluated Ca-MOF shows the shortest clotting time (39 & PLUSMN; 0.2 s) and lowest blood loss (0.14 & PLUSMN; 0.2 g) in the rat-tail amputation model compared to the control and commercially available haemostatic drug tranexamic acid. With the enhanced coagulation capacity and associated biocompatibility, the developed calcium-aspartate bio-MOF could act as a safe and effective haemostatic agent and provide a unique concept for using synthetic porous materials for the management of excessive bleeding.

Automated summary

This study synthesizes amino acid-based MOF using l-aspartic acid and calcium, and optimizes the reaction conditions. Despite low porosity and surface area, the Ca-MOF shows high impact on haemostatic property. It has the shortest clotting time and lowest blood loss in a rat-tail amputation model, suggesting its potential as a safe and effective haemostatic agent.