Injectable Thermo-Responsive Peptide Hydrogels and Its Enzyme Triggered Dynamic Self-Assembly.

Area of Science:

• Biomaterials Science
• Polymer Chemistry
• Drug Delivery Systems

Background:

• Injectable hydrogels are crucial for controlled drug delivery.
• Stimuli-responsive hydrogels offer spatiotemporal control over drug release.
• Polypeptide-based hydrogels are attractive for biomedical applications.

Purpose of the Study:

• To develop novel in situ forming polypeptide hydrogels with thermal responsiveness.
• To engineer enzyme-triggered dynamic self-assembly for drug delivery.
• To investigate the biocompatibility of these hydrogels.

Main Methods:

• Synthesis of diblock random copolymers mPEG-b-P(Glu-co-Tyr) with varying L-glutamic acid (Glu) side chains.
• Characterization of hydrogel formation, thermal responsiveness, and sol-gel transition.
• Investigating enzyme-triggered self-assembly and structural transformation using alkaline phosphatase (ALP).
• Assessing cell viability of copolymers with MC3T3-E1 and Hela cells.

Main Results:

• Successfully synthesized polypeptide hydrogels exhibiting thermal responsiveness.
• Demonstrated enzyme-triggered dynamic self-assembly and structural transformation (spheres to sheets) upon dephosphorylation by ALP.
• Confirmed good biocompatibility with MC3T3-E1 and Hela cells (viability >80% at 1000 μg/mL).
• The copolymers showed tunable properties based on Glu side chain modifications.

Conclusions:

• Developed a facile strategy for creating in situ forming, thermally responsive polypeptide hydrogels.
• Achieved enzyme-triggered dynamic self-assembly, enabling tunable drug delivery.
• The hydrogels and their self-assemblies exhibit significant potential for biomedical applications, particularly in drug delivery.