Preliminary in vitro hemocompatibility assessment of biopolymeric hydrogels for versatile biomedical applications

Biomaterials utilized for various medical applications are expected to be hemocompatible, i.e., they don’t cause any adverse effect on red blood cells in contact with them. Presently, hydrogels prepared from biopolymers with three-dimensional porous networks are considered as prime candidates for biomedical applications. The present study conducted preliminary in vitro assessment of hemocompatibility of different biopolymers, various chemical reagents including cross-linkers, grafting monomers and free radical initiator required for the synthesis of hydrogels of biomedical importance and finally of the synthesized hydrogels. The synthesized hydrogels were characterized using swelling studies, FTIR and mechanical strength. Herein, in vitro hemolytic analysis was utilized as a preliminary indicator to assess the hemocompatibility of a biomaterial. Out of the biopolymers studied (starch, carboxymethyl cellulose, sodium alginate, karaya gum, chitosan, xanthan gum, β-cyclodextrin, gelatin and dextrin), the degree of hemolysis was found to be minimum for chitosan (0.08%) and maximum for β-cyclodextrin (44.57%). The presence of higher charge density seems to be negative for hemocompatibility. Further, the cross-linkers including N , N ′-methylenebisacrylamide, glutaraldehyde, maleic acid, fumaric acid, DL-malic acid and citric acid were studied for their hemocompatibility. The maleic acid and fumaric acid were found to possess better compatibilities in the range of 3.25% and 4.43%, respectively. The natural or synthetic origin of a cross-linker does not seem to be a consideration for hemocompatibility. Further, most of the synthesized biopolymer based hydrogels displayed better hemocompatibility in comparison to the starting precursor materials owing to their unique surface chemistry and distribution of the hydrophilic groups. The acrylamide grafted hydrogels displayed hemolytic activity (2.23%) in safer range in comparison to the acrylic acid grafted hydrogels (68.15%). The presence of certain functional groups containing oxygen and nitrogen and moderate negative charge improved hemocompatibility in comparison to carbon containing functional groups and high negative charge density. The hemolytic activity of hydrogels was observed to be increased manifold in the presence of nanoparticles incorporated into hydrogels to improve their physical characteristics. The results indicate that the careful selection of biopolymers, cross-linkers, grafting monomers and further tuning of surface chemistry by controlling functional groups and their charge density over a biomaterial is prerequisite to prevent protein adsorption, inflammatory response and lysis of RBCs in the living host. Undoubtedly, in vitro hemocompatibility analysis is not a satisfactory indicator for measuring hemolytic activity of biomaterials, but can definitely help in preliminary assessment as indicated by the results of the present study. These bio-based hydrogels within safer limits of hemocompatibility can be prime materials for many biomedical applications including scaffolds in tissue engineering, implants, prosthetic devices, antibacterial and dental materials, drug delivery carriers, biosensors and bio adhesives. Graphical abstract