ATP-responsive DNA hydrogel enables on-demand FGF21 release, enhancing muscle cell proliferation and differentiation

Effective regeneration of injured skeletal muscle remains a significant clinical challenge, often hampered by the lack of precise spatiotemporal control over therapeutic delivery. Current strategies struggle with premature drug release and off-target distribution, limiting efficacy and safety. This necessitates innovative approaches capable of localized, controlled release of regenerative factors. Cytokines like fibroblast growth factor 21 (FGF21) are crucial for tissue repair, but their systemic administration can lead to rapid clearance and adverse effects, highlighting the need for targeted delivery systems.

Researchers developed an ATP-responsive injectable DNA hybrid hydrogel through rational DNA sequence design and optimized cross-linking methodologies. This three-dimensional network was engineered to efficiently encapsulate various cytokines, including FGF21. The hydrogel's design allows it to specifically respond to characteristic increases in ATP concentration fluctuations within the local tissue microenvironment. This responsiveness enables the precise, "on-demand release" of encapsulated cytokines, aiming to promote localized therapeutic effects and enhance muscle regeneration.

The designed DNA hybrid hydrogel demonstrated the ability to efficiently encapsulate a diverse range of cytokines, crucial for tissue repair. Its core finding is the ATP-responsive release mechanism, allowing for precise control over cytokine delivery in response to local ATP concentration fluctuations. This targeted release was shown to promote the proliferation and differentiation of muscle cells, indicating its potential for regenerative applications. Furthermore, the hydrogel exhibited excellent biocompatibility, suggesting a favorable safety profile for in vivo use. The "on-demand release" capability is critical for enhancing therapeutic efficacy by preventing premature drug release and minimizing off-target distribution. This system creates a more favorable and functionally optimized microenvironment for muscle regeneration.

The ATP-responsive injectable DNA hybrid hydrogel enables precise, on-demand cytokine release, directly promoting muscle cell proliferation and differentiation.