Artificial Extracellular Matrix Composed of Heparin-Mimicking Polymers for Efficient Anticoagulation and Promotion of Endothelial Cell Proliferation

Heparin-mimicking polymers have emerged as an alternative to heparin to construct effective and safe anticoagulant surfaces. However, the present heparin-mimicking polymers are usually limited to the combinations of glucose and sulfonic acid units, and the structure origin of their anticoagulant properties remains vague. Inspired by the structure of natural heparin, we synthesized a series of novel heparin-mimicking polymers (named GSAs) composed of three units, glucose, sulfonic acid, and carboxylic acid. Then, we constructed artificial extracellular matrices composed of GSAs and two typical cationic polymers, polyethyleneimine and chitosan, to investigate the anticoagulation and endothelialization of GSAs. By changing the ratio of the three units, their functions in the matrices were studied systematically. We found that an increase in the sulfonic acid content enhanced surface anticoagulant activity, an increase in glucose and sulfonic acid content promoted the proliferation of human umbilical vein vascular endothelial cells, and an increase in the carboxylic acid content inhibited the adherence of human umbilical vein vascular smooth muscle cells. This work uncovers the important role of the GSAs structure to the anticoagulation properties, which sheds new light on the design and preparation of heparin-mimicking polymers for practical engineering applications.