DNA-Based Daisy Chain Rotaxane Nanocomposite Hydrogels as Dual-Programmable Dynamic Scaffolds for Stem Cell Adhesion.

Area of Science:

• Biomaterials Science
• Nanotechnology
• Synthetic Biology

Background:

• Interlocked DNA nanostructures enable nanoscale movements like sliding and contraction.
• Regulating larger matrices with nanoscale movements and developing applications remains challenging.

Purpose of the Study:

• To assemble DNA-based daisy chain rotaxane nanostructures (DNA-DCRs).
• To integrate DNA-DCRs into hydrogels for tunable mechanical properties and dynamic biointerfaces.
• To investigate the effect of DNA-DCRs on human mesenchymal stem cell (hMSC) adhesion.

Main Methods:

• Assembly of DNA-DCRs with tunable mechanical states (fixed extended state, sliding state, fixed contracted state) using toehold-mediated strand displacement reaction (SDR).
• Incorporation of DNA-DCRs into hydrogel matrices to create interlocked hydrogels with modulable stiffness via hybridization chain reaction (HCR).
• Functionalization of DNA-DCRs with cell adhesion ligands (RGD) and evaluation of hMSC adhesion on modified hydrogels.

Main Results:

• Interlocked hydrogels exhibited modulable stiffness, regulated by DNA-DCR elongation and HCR treatment.
• hMSCs showed lower adhesion on hydrogels with decreased stiffness (swollen state).
• RGD-modified DNA-DCR hydrogels demonstrated enhanced hMSC adhesion when RGD ligands were mobile (sliding state) compared to fixed states.

Conclusions:

• DNA-DCR nanocomposite hydrogels offer dual-programmable functions: swelling adjustment and ligand mobility.
• These dynamic scaffolds can regulate stem cell adhesion through cross-scale regulation from DNA nanostructures to the hydrogel matrix.
• This work presents a novel pathway for DNA-based materials with tunable properties for biomedical applications.