A Regenerative Cardiac Patch Based on a Pressure-Compacted and Spider Silk Reinforced Fibrin Matrix

Background: Numerous operations in congenital cardiac surgery require the use of patch materials. However, currently available synthetic or xenogeneic cardiac patches are prone to inflammation, biofilm formation, and calcification due to insufficient biocompatibility. On the other hand, patches excised from autologous pericardium are highly variable in quality and can only be obtained in limited quantities in selected patients. Thus, there is an ongoing need for innovative patch materials with immediate availability and superior hemo- and biocompatibility, especially for early repairs of congenital heart defects. For this purpose, fibrin is a promising biomaterial with unique biological and regenerative properties. However, unprocessed fibrin matrices exhibit insufficient mechanical stability to facilitate suturing and to withstand the mechanical forces in the heart.

Method: Two methods were combined to increase the mechanical stability of fibrin matrices in bioartificial cardiac patches. First, Nephila edulis spider silk-cocoons were fixated in a custom-built circular mold (diameter: 3 cm) and a solution containing human fibrinogen, thrombin, and Factor XIII was molded around the reinforcing spider silk framework. Second, vertical pressure of 2 kg was applied on top of the patch for 60 minutes after initial polymerization to achieve compaction of the fibrin matrix. Following thorough biomechanical characterization in vitro, pressure-compacted spider silk reinforced patches were implanted into the right ventricular outflow tract of sheep (n = 3) as a pilot in vivo experiment.

Results: Pressure compaction reduced the wall thickness of fibrin matrices to less than 1 mm. The resulting spider-silk reinforced fibrin patches resisted supraphysiological pressures of well over 2,000 mm Hg. Embedding of spider silk increased the tensile force 1.8-fold and tensile strength 1.45-fold (p < 0.001), resulting in a final strength of 1.07 MPa. Furthermore, in vitro long-term load testing, storage testing, and sewing tests showed satisfactory results. The patches proofed suitable for surgical implantation in sheep and remained stable during the study period of 3 months.

Conclusion: Combining a spider-silk framework with a highly compacted fibrin matrix is a suitable technique to generate biologically active cardiac patches with sufficient biomechanical stability to allow surgical handling and to withstand physiological and supraphysiological mechanical forces. Due to their regenerative potential, the fibrin based patches may become a valuable therapeutic option, especially for early repairs of congenital heart defects.

Publication History

Article published online:
12 February 2022