Thermoreversible and Injectable ABC Polypeptoid Hydrogels: Controlling the Hydrogel Properties through Molecular...

Area of Science:

• Polymer Chemistry
• Materials Science
• Biotechnology

Background:

• Development of advanced biomaterials for tissue engineering and drug delivery is crucial.
• Tunable hydrogels with controlled properties are highly sought after for various biomedical applications.
• Polypeptoids offer a versatile platform for creating functional polymeric materials.

Purpose of the Study:

• To synthesize and characterize novel ABC triblock copolypeptoids.
• To investigate the thermoresponsive sol-to-gel transition properties of these copolypeptoids in aqueous media.
• To evaluate the potential of the resulting hydrogels for tissue engineering and enzyme encapsulation applications.

Main Methods:

• Sequential primary amine-initiated ring-opening polymerization of N-substituted N-carboxyanhydride monomers.
• Rheological measurements to characterize sol-gel transitions and mechanical properties.
• In vitro cytotoxicity assays (alamarBlue, PicoGreen) and gene expression analysis (quantitative PCR) using human adipose derived stem cells (hASCs).
• Enzyme encapsulation studies with horseradish peroxidase (HRP).

Main Results:

• Well-defined ABC triblock copolypeptoids (poly(N-allyl glycine)-b-poly(N-methyl glycine)-b-poly(N-decyl glycine)) were synthesized.
• The copolypeptoids exhibited rapid, reversible, and tunable sol-to-gel transitions with increasing temperature at low concentrations (2.5-10 wt %).
• Tunable gelation temperatures (26.2-60.0 °C) and mechanical moduli (G' 0.2-780 Pa, E 0.5-2346 Pa at 37 °C) were achieved by controlling composition and concentration.
• Injectable hydrogels showed minimal cytotoxicity to hASCs, induced chondrogenesis (up-regulated Col2a1, down-regulated ANGPT1), and successfully encapsulated HRP with retained activity.

Conclusions:

• The synthesized ABC block copolypeptoids form injectable, thermoresponsive hydrogels with tunable properties.
• These hydrogels demonstrate biocompatibility, chondrogenic potential, and utility for enzyme encapsulation.
• The polypeptoid hydrogel platform shows significant promise for tissue engineering and protein storage applications.