Dynamically Cross-Linked Granular Hydrogels for 3D Printing and Therapeutic Delivery

Area of Science:

• Biomaterials Science
• Tissue Engineering
• Polymer Chemistry

Background:

• Granular hydrogels offer advantages over bulk hydrogels for tissue engineering and 3D printing, including injectability and porosity.
• Improving the structural stability of granular hydrogels post-injection is crucial for their therapeutic applications.
• Reversible and dynamic covalent cross-linking presents a novel strategy to enhance hydrogel properties.

Purpose of the Study:

• To develop granular hydrogels with enhanced structural stability via interparticle cross-linking using reversible dynamic covalent bonds.
• To investigate the injectability, self-healing, and mechanical properties of these novel granular hydrogels.
• To evaluate the potential of these hydrogels as scaffolds for cell recruitment and therapeutic delivery.

Main Methods:

• Fragmenting photo-cross-linked bulk hydrogels into aldehyde or hydrazide-functionalized microgels derived from chondroitin sulfate.
• Inducing interparticle cross-linking through reversible hydrazone bonds by mixing functionalized microgels.
• Characterizing the resulting granular hydrogels for mechanical stability, shear-thinning, self-healing, porosity, and growth factor release.

Main Results:

• The developed granular hydrogels exhibited shear-thinning and self-healing properties, enabling effective injectability and 3D printing.
• High mechanical stability was achieved without the need for secondary cross-linking steps.
• Enhanced porosity and sustained release of growth factors from the hydrogels promoted synergistic cell recruitment.

Conclusions:

• Reversible interparticle cross-linking is a viable strategy for improving the structural stability of granular hydrogels.
• These engineered granular hydrogels are promising injectable and 3D printable scaffolds for tissue engineering and therapeutic delivery.
• The study underscores the potential of dynamic covalent chemistry in designing advanced biomaterials for regenerative medicine.