A Visible Light-Cross-Linkable, Fibrin-Gelatin-Based Bioprinted Construct with Human Cardiomyocytes and Fibroblasts

Area of Science:

• Biomaterials Science
• Tissue Engineering
• Cardiovascular Research

Background:

• Fibrin is widely used in regenerative medicine and shares properties with surgical glues.
• Developing advanced bioinks is crucial for creating functional cardiac tissue constructs.
• Patient-specific materials like fibrin offer unique advantages in biomedical applications.

Purpose of the Study:

• To create a stable, printable bioink incorporating fibrin for cardiac cell encapsulation.
• To evaluate the viability, proliferation, and cardiac marker expression of cardiomyocytes within the bioink.
• To explore the potential of the bioink for co-culturing cardiomyocytes and cardiac fibroblasts.

Main Methods:

• Fabrication of a photo-polymerizable gelatin-based bioink with added fibrin.
• Bioprinting of cardiac cell-laden constructs using human induced pluripotent stem cell-derived cardiomyocytes (iPS-CM) or CM cell lines and cardiac fibroblasts (CF).
• Two-step cross-linking procedure involving visible light for furfuryl-gelatin and chemical cross-linking for fibrinogen using thrombin and calcium chloride.

Main Results:

• The resulting fibrin-gelatin constructs exhibited a highly porous, networked structure with long-term in vitro stability.
• Cardiomyocytes demonstrated excellent viability, proliferation, and expression of the cardiac troponin I marker.
• The bioink successfully supported the co-culture and coupling of cardiomyocytes and cardiac fibroblasts.

Conclusions:

• The developed fibrin-gelatin bioink is suitable for fabricating stable, cell-laden cardiac constructs.
• This enhanced cardiac construct provides a valuable platform for in vitro drug cytotoxicity screening.
• The bioink facilitates the study of cardiomyocyte-fibroblast interactions, crucial for understanding cardiac physiology and disease.