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.