Controlled Cryogelation and Catalytic Cross-Linking Yields Highly Elastic and Robust Silk Fibroin Scaffolds.

Silk biomaterials with tunable mechanical properties and biological properties are of special importance for tissue engineering. Here, we fabricated silk fibroin (SF, from silk) scaffolds from cryogelation under controlled temperature and catalytic cross-linking conditions. Structurally, the cryogelled scaffolds demonstrated a greater β-sheet content but significantly smaller β-sheet domains compared to that without chemical cross-linking and catalyst. Mechanically, the cryogelled scaffolds were softer and highly elastic under tension and compression. The 120% tensile elongation and >85% recoverable compressive strain were among the best properties reported for SF scaffolds. Cyclic compression tests proved the robustness of such scaffolds to resist fatigue. The mechanical properties, as well as the degradation rate of the scaffolds, can be fine-tuned by varying the concentrations of the catalyst and the cross-linker. For biological responses, rat bone mesenchymal stem cell (rBMSC) culture studies demonstrated that cryogelled SF scaffolds supported better cell attachment and proliferation than the routine freeze-thawed scaffolds. The subcutaneous implantation results showed excellent histocompatibility and tissue ingrowth for the cryogelled SF scaffolds. This straightforward approach of enhanced elasticity of SF scaffolds and fine-tunability in mechanical performances, suggests a promising strategy to develop novel SF biomaterials for soft tissue engineering and regenerative medicine.