Designing Viscoelastic Gelatin-PEG Macroporous Hybrid Hydrogel with Anisotropic Morphology and Mechanical Properties for Tissue Engineering Application

The mechanical properties of scaffolds play a vital role in regulating key cellular processes in tissue development and regeneration in the field of tissue engineering. Recently, scaffolding material design strategies leverage viscoelasticity to guide stem cells toward specific tissue regeneration. Herein, we designed and developed a viscoelastic Gel-PEG hybrid hydrogel with anisotropic morphology and mechanical properties using a gelatin and functionalized PEG (as a crosslinker) under a benign condition for tissue engineering application. The chemical crosslinking/grafting reaction was mainly involved between epoxide groups of PEG and available functional groups of gelatin. FTIR spectra revealed the hybrid nature of Gel-PEG hydrogel. The hybrid hydrogel showed good swelling behavior (water content > 600%), high porosity and pore interconnectivity suitable for tissue engineering application. Simple unidirectional freezing followed by a freeze-drying technique allowed the creation of structurally stable 3D anisotropic macroporous architecture that showed tissue-like elasticity and was capable of withstanding high deformation (50% strain) without being damaged. The tensile and compressive modulus of Gel-PEG hybrid hydrogel were found to be 0.863 MPa and 0.330 MPa, respectively, which are within the range of normal human articular cartilage. In-depth mechanical characterizations showed that the Gel-PEG hybrid hydrogel possessed natural-tissue-like mechanics such as non-linear and J-shaped stress-strain curves, stress softening effect, high fatigue resistance and stress relaxation response. A month-long hydrolytic degradation test revealed that the hydrogel gradually degraded in a homogeneous manner over time but maintained its structural stability and anisotropic mechanics. Overall, all these interesting features provide a potential opportunity for Gel-PEG hybrid hydrogel as a scaffold in a wide range of tissue engineering applications.