Aptamer-functionalized stiff hydrogel for enhanced BMSC enrichment and osteogenesis

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Tissue Engineering

Background:

• Bone tissue engineering requires strategies to recruit endogenous stem cells and promote their osteogenic differentiation.
• Current cell-free approaches often struggle with efficient stem cell sourcing and controlled lineage induction.
• Developing integrated systems that address both challenges is critical for effective bone regeneration.

Purpose of the Study:

• To develop a combined "enrich-and-differentiate" system for bone regeneration.
• To create a stiffness-gradient hydrogel functionalized with a cell-enriching aptamer for enhanced osteogenesis.
• To evaluate the synergistic effects of cell enrichment and mechanical cues on bone marrow-derived mesenchymal stem cells (BMSCs) differentiation.

Main Methods:

• Fabrication of a stiffness-gradient hydrogel (4.5-33 kPa) incorporating a cell-enriching aptamer (Apt19s).
• Assessment of endogenous BMSC recruitment to the hydrogel scaffold.
• Evaluation of osteogenic differentiation markers, including alkaline phosphatase (ALP) activity, RUNX2/osteocalcin (OCN) gene expression, and mineralization.

Main Results:

• The Apt19s-functionalized hydrogel successfully enriched endogenous BMSCs at the scaffold site.
• The high-stiffness niche (~33 kPa) promoted osteogenic differentiation.
• Combined "enrich-and-differentiate" cues resulted in significantly enhanced osteogenic outcomes (>2-fold ALP activity, 186.5% RUNX2/OCN upregulation) exceeding additive effects.

Conclusions:

• The integrated platform effectively addresses the dual challenges of endogenous cell sourcing and osteogenic induction in a cell-free manner.
• This stiffness-gradient hydrogel system offers a promising strategy for advancing bone tissue engineering and regeneration.
• The synergistic approach demonstrates superior osteogenic potential compared to individual cues, paving the way for practical biomaterials.