An interpenetrating network-strengthened and toughened hydrogel that supports cell-based nucleus pulposus regeneration.

Hydrogel is a suitable scaffold for the nucleus pulposus (NP) regeneration. However, its unmatched mechanical properties lead to implant failure in late-stage disc degeneration because of structural failure and implant extrusion after long-term compression. In this study, we evaluated an interpenetrating network (IPN)-strengthened and toughened hydrogel for NP regeneration, using dextran and gelatin as the primary network while poly (ethylene glycol) as the secondary network. The aim of this study was to realize the NP regeneration using the hydrogel. To achieve this, we optimized its properties by adjusting the mass ratios of the secondary/primary networks and determining the best preparation conditions for NP regeneration in a series of biomechanical, cytocompatibility, tissue engineering, and in vivo study. We found the optimal formulation of the IPN hydrogel, at a secondary/primary network ratio of 1:4, exhibited high toughness (the compressive strain reached 86%). The encapsulated NP cells showed increasing proliferation, cell clustering and matrix deposition. Furthermore, the hydrogel could support long-term cell retention and survival in the rat IVDs. It facilitated rehydration and regeneration of porcine degenerative NPs. In conclusion, this study demonstrates the tough IPN hydrogel could be a promising candidate for functional disc regeneration in future.

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