Random sequence-guided crosslinking for on-demand injectable HA-DNA hydrogels supporting neural progenitor cells.

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Nanotechnology

Background:

• Hyaluronic acid (HA) hydrogels crosslinked with DNA (HA-DNA hydrogels) are promising for regenerative medicine.
• Premature network formation due to nonspecific DNA hybridization limits their practical application.

Purpose of the Study:

• To develop an on-demand injectable HA-DNA hydrogel with controlled gelation kinetics.
• To engineer a system that minimizes nonspecific crosslinking while maintaining functional hybridization.

Main Methods:

• A dual-tube hybrid-bridge design was employed.
• Sequence-level randomization (N=8) was introduced into the DNA crosslinker overlap domain.
• In silico analysis, rheological testing, and cell encapsulation studies were performed.

Main Results:

• Sequence randomization significantly reduced nonspecific self-dimerization.
• The optimized hydrogel demonstrated suppressed pre-gelation and rapid, homogeneous gelation upon mixing.
• Uniform neural progenitor cell encapsulation maintained high viability and neural stemness marker expression.

Conclusions:

• The sequence-optimized dual-tube HA-DNA hydrogel offers controlled gelation for injectable applications.
• This platform supports neural progenitor cell survival and differentiation.
• The developed hydrogel is suitable for minimally invasive neural tissue engineering.