Genetically Encoded XTEN-based Hydrogels with Tunable Viscoelasticity and Biodegradability for Injectable Cell...

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Protein Engineering

Background:

• Cell transplantation faces challenges with poor cell survival and engraftment.
• Current injectable biomaterials often use immunogenic or ill-defined polymers.
• There is a need for advanced biomaterials that support cell viability and therapeutic efficacy.

Purpose of the Study:

• To develop a novel, injectable, shear-thinning, and self-healing hydrogel for cell transplantation.
• To utilize XTEN, a non-immunogenic polypeptide, for creating advanced biomaterials.
• To engineer a single-component protein-based hydrogel with tunable properties.

Main Methods:

• Engineered a telechelic recombinant protein hydrogel based on XTEN flanked by cartilage oligomeric matrix protein-derived coil domains.
• Utilized homopentameric coiled-coil bundling for physical crosslinking, enabling shear thinning and self-healing.
• Introduced point mutations to genetically program material viscoelasticity and biodegradability.

Main Results:

• Developed a single-component, injectable hydrogel with rapid shear-thinning and self-healing properties.
• Demonstrated that mutations allow for tunable material properties like viscoelasticity and biodegradability.
• Showcased protection and sustained viability of encapsulated human fibroblasts, hepatocytes, HEK cells, and hESC-CMs through in vitro culture and in vivo implantation in mice.

Conclusions:

• The developed XTEN-based hydrogels are promising injectable biomaterials for cell transplantation.
• These materials enhance cell viability and engraftment, addressing key limitations in cell therapy.
• The tunable and non-immunogenic nature of these hydrogels offers significant potential for both in vitro and in vivo applications.