Injectable aptamer-functionalized nucleic acid-collagen hydrogels as a bioactive platform for angiogenic applications

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Vascular Biology

Background:

• Nucleic acid-collagen complexes (NACCs) are self-assembled biomaterials using type I collagen and single-stranded DNA (ssDNA).
• Angiogenesis, the formation of new blood vessels, is crucial for tissue repair and regeneration.

Purpose of the Study:

• To develop injectable NACCs functionalized with a vascular endothelial growth factor receptor 2 (VEGFR-2) activating aptamer for promoting localized angiogenesis.
• To evaluate the stability, injectability, in vitro biological activity, and in vivo efficacy of these engineered NACCs.

Main Methods:

• Fabrication of NACCs via self-assembly of collagen and ssDNA, functionalized with a VEGFR-2 aptamer.
• Assessment of aptamer stability in nuclease-rich environments and hydrogel rheology for injectability.
• In vitro studies using endothelial cells in 3D culture to evaluate cell behavior and vascular structure formation.
• In vivo subcutaneous implantation in mice to assess host cell infiltration, tissue remodeling, angiogenesis, and systemic inflammation via cytokine analysis.

Main Results:

• The VEGFR-2 aptamer within NACCs remained protected from degradation and the hydrogel exhibited shear-thinning properties for 25G needle injectability.
• In vitro, NACCs supported endothelial cell attachment, spreading, proliferation, and the formation of vascular-like structures.
• In vivo, implanted mice showed significant host cell infiltration, tissue remodeling, and robust new blood vessel formation without exogenous factors.
• Minimal systemic inflammation was observed, with low or undetectable cytokine levels in plasma, confirming biocompatibility.

Conclusions:

• ssDNA aptamer-functionalized NACCs form a bioactive, injectable hydrogel platform for promoting angiogenesis.
• This platform demonstrates translational relevance for regenerative medicine by supporting pro-angiogenic remodeling and exhibiting excellent biocompatibility.