Add time:08/24/2019         Source:sciencedirect.com

To strengthen the mechanical properties of a fibrin gel and improve its applicability as a scaffold for tissue engineering (TE) applications, a strategy for the in situ preparation of the interpenetrating network (IPN) of fibrin and hyaluronic acid (HA) was developed on the basis of simultaneous and orthogonal fibrinogenesis and disulfide cross-linking. The synthetic pathway included the preparation of mutually reactive HA derivatives bearing thiol and 2-dithiopyridyl groups. Combining thiol-derivatized HA with thrombin and 2-dithiopyridyl-modified HA with fibrinogen and then mixing the obtained liquid formulations afforded IPNs with fibrin-resembling fibrillar architectures at different ratios between fibrin and HA networks. The formation of two networks was confirmed by conducting reference experiments with the compositions lacking one of the four components. The composition of 2% (w/v) fibrin and 1% (w/v) HA showed the highest storage modulus (G′), as compared with the single network counterparts. The degradation of fibrin in IPN hydrogels was slower than that in pure fibrin gels both during incubation of the hydrogels in a fibrin-cleaving nattokinase solution and during the culturing of cells after their encapsulation in the hydrogels. Together with the persistence of HA network, it permitted longer cell culturing time in the IPN. Moreover, the proliferation and spreading of MG63 cells that express the hyaluronan receptor CD44 in IPN hydrogel was increased, as compared with its single network analogues. These results are promising for tunable ECM-based materials for TE and regenerative medicine.

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