Bidirectional Enzyme Inhibition and Activation for In Situ Formation of Injectable Hydrogel Using a Bispecific...

Area of Science:

• Biomaterials Science
• Biotechnology
• Biomedical Engineering

Background:

• Injectable hydrogels are promising for regenerative medicine and drug delivery.
• Controlling the gelation speed of in situ injectable hydrogels is crucial for successful clinical application but remains a significant challenge.
• Enzyme-mediated hydrogel formation offers a pathway for in situ gelation.

Purpose of the Study:

• To investigate the use of bispecific aptamers and complementary sequences as a bidirectional control system.
• To demonstrate the modulation of enzyme-mediated hydrogel formation kinetics using this aptamer-based system.
• To control the gelation rate of fibrin hydrogels for improved injectable applications.

Main Methods:

• Design and synthesis of a bispecific thrombin-binding aptamer.
• Evaluation of the aptamer's inhibitory effect on thrombin activity.
• Assessment of the effect of the complementary sequence on reversing aptamer inhibition and modulating fibrin gelation kinetics.

Main Results:

• The bispecific aptamer effectively inhibited thrombin activity, significantly slowing fibrin hydrogel formation.
• Addition of the complementary sequence reversed the aptamer's inhibition, leading to thrombin activation.
• This dynamic system allowed for accelerated fibrin formation kinetics, demonstrating bidirectional control.

Conclusions:

• Bispecific aptamers and complementary sequences provide an effective dynamic control system for enzyme-catalyzed hydrogel formation.
• This approach offers precise temporal control over injectable hydrogel gelation kinetics.
• The developed system has significant potential for advancing applications in regenerative medicine and drug delivery.