Tuning chitosan properties to enhance blood coagulation

The search for new hemostatic materials remains a priority for researchers, as the problem of uncontrolled hemorrhage during surgical interventions or traumatic injuries represents a significant challenge. The objective of the study was to identify novel polysaccharide structures with enhanced hemostatic properties based on chitosan. The number of chitosan derivatives with two substituents was synthesized and characterized by ¹H NMR, FTIR. One of these was a structural analogue of L-DOPA - N-(3,4-dihydroxybenzyl), while the other comprised fragments of different nature, including hydrophobic N-(4-(tetradecyloxy)benzyl), negatively charged groups N-(4-carboxybenzyl) and aminocaproic acid residue. The hemostatic potential of the novel compounds was evaluated in vitro/in vivo on human blood and in mouse model of tail bleeding. Solutions of chitosan derivatives showed the ability to aggregate with blood about 3-5 times higher than chitosan in a neutral saline medium (0.9 % NaCl) and slightly acidic conditions both when (Ca²⁺) was added and in the case of citrated blood. Chitosan derivatives demonstrated low toxicity (3T3, HepG2 and Huh7) and did not induce plasma coagulation or platelet aggregation at low concentrations. The novel compounds can be used to modify the surface of biomaterials in order to improve their hemostatic properties.