Heparinized collagen-based hydrogels for tissue engineering: physical, mechanical and biological properties

Area of Science:

• Biomaterials Science
• Vascular Engineering
• Biochemistry

Background:

• Collagen, a primary vascular extracellular matrix protein, possesses weak antigenicity, making it suitable for vascular graft coatings.
• Heparinization is a preferred method to impart antithrombotic properties to collagen, improving blood compatibility and enabling bioactive molecule delivery.

Purpose of the Study:

• To create heparinized collagen-based hydrogels using pH-driven self-assembly.
• To evaluate the physicochemical and biocompatibility properties of these hydrogels for vascular graft applications.
• To assess the antithrombotic efficacy and long-term heparin retention of the developed coatings.

Main Methods:

• pH-driven self-assembly to form collagen-based hydrogels with incorporated low molecular weight heparin (LMWH) or unfractionated heparin (UFH).
• Physicochemical characterization: gelation kinetics, spreading, viscoelasticity, microstructure, and heparin quantification.
• Biocompatibility assessment: cytocompatibility, albumin adsorption, and cell viability.
• Antithrombotic evaluation: heparin release, activated partial thromboplastin time (aPTT), thrombin time (TT), and thrombin generation assays.

Main Results:

• Higher loading capacity for unfractionated heparin (60-80%) compared to low molecular weight heparin (20%).
• Increased heparin concentration (6 IU/mL) resulted in softer hydrogels with enhanced spreadability and improved antithrombotic activity (delayed coagulation, abolished thrombin generation).
• Hydrogels exhibited a layered, networked architecture and maintained heparin release for at least seven days, demonstrating biocompatibility with low albumin adsorption and no impact on cell viability.

Conclusions:

• Successfully developed heparinized collagen hydrogels with tunable physicochemical properties and significant antithrombotic capabilities.
• These hydrogels demonstrate excellent biocompatibility and long-term heparin retention, suitable for advanced blood-contacting materials.
• The findings highlight the potential of these coatings for developing efficient and safe vascular grafts.