Structuring supramolecular hyaluronan hydrogels via peptide self-assembly for modulating the cell microenvironment.

Area of Science:

• Biomaterials Science
• Tissue Engineering
• Cell Biology

Background:

• Synthetic extracellular matrices (ECMs) are crucial for in vitro cell culture, but achieving biomimicry remains a challenge.
• Designing synthetic matrices that emulate natural ECM composition and structure is essential for native-like cellular environments.
• Current in vitro models often lack the complexity to fully recapitulate cell-matrix interactions.

Purpose of the Study:

• To develop novel biomimetic hydrogels as extracellular matrix (ECM) surrogates using supramolecular fabrication.
• To investigate the self-assembly and tunable properties of peptide-hyaluronan (HA) hydrogels.
• To evaluate the potential of these hydrogels for in vitro cell culture and stem cell applications.

Main Methods:

• Supramolecular fabrication of hydrogels by combining native hyaluronan (HA) with rationally designed cationic amphipathic peptides [(KI)nK].
• Tuning of mechanical properties and microstructure by altering peptide sequence length (n=2-6).
• Characterization of peptide self-assembly into β-sheet nanostructures and hydrogel formation via electrostatic complexation with HA.

Main Results:

• Peptide sequence length dictates hydrogel phase behavior: shorter peptides form single-phase hydrogels, while longer peptides induce phase separation with HA.
• The resulting (KI)nK-HA hydrogels exhibit tunable viscoelastic properties.
• These hydrogels promote the formation of human mesenchymal stem cell (MSC) spheroids, which subsequently disassemble over time.

Conclusions:

• Peptide-hyaluronan hydrogels fabricated via supramolecular assembly serve as promising biomimetic ECM surrogates.
• Tunable physical and biochemical properties make these hydrogels versatile for in vitro cell culture.
• The developed hydrogels show potential as a platform for stem cell therapy applications.