Formation and stability of interpenetrating polymer network hydrogels consisting of fibrin and hyaluronic acid for tissue engineering

Fibrin gel is widely used as a tissue engineering scaffold. However, it has poor mechanical properties, which often result in rapid contraction and degradation of the scaffold. An interpenetrating polymer network (IPN) hydrogel composed of fibrin and hyaluronic acid–tyramine (HA–Tyr) was developed to improve the mechanical properties. The fibrin network was formed by cleaving fibrinogen with thrombin, producing fibrin monomers that rapidly polymerize. The HA network was formed through the coupling of tyramine moieties using horseradish peroxidase (HRP) and hydrogen peroxide (H2O2). The degree of crosslinking of the HA–Tyr network can be tuned by varying the H2O2 concentration, producing IPN hydrogels with different storage moduli (G′). While fibrin gels were completely degraded in the presence of plasmin and contracted when embedded with cells, the shape of the IPN hydrogels was maintained due to structural support by the HA–Tyr networks. Cell proliferation and capillary formation occurred in IPN hydrogels and were found to decrease with increasing G′ of the hydrogels. The results suggest that fibrin–HA–Tyr IPN hydrogels are a potential alternative to fibrin gels as scaffolds for tissue engineering applications that require shape stability.