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

Yichen Yuan; Yejiao Shi; Jayati Banerjee; Amin Sadeghpour; Helena S Azevedo

doi:10.1016/j.mtbio.2023.100598

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

Mater Today Bio. 2023 Mar 2:19:100598. doi: 10.1016/j.mtbio.2023.100598. eCollection 2023 Apr.

Authors

Yichen Yuan^{1

2}, Yejiao Shi^{1

3}, Jayati Banerjee¹, Amin Sadeghpour⁴, Helena S Azevedo^{1

5

6}

Affiliations

¹ School of Engineering and Materials Science & Institute of Bioengineering, Queen Mary University of London, London, E1 4NS, UK.
² Zhejiang Lab, Hangzhou, 311121, Zhejiang, PR China.
³ Institute of Translational Medicine, Shanghai University, Shanghai, 200444, PR China.
⁴ School of Food Science and Nutrition, University of Leeds, Leeds, LS2 9JT, UK.
⁵ i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal.
⁶ INEB - Instituto de Engenharia Biomédica, Universidade do Porto, Rua Alfredo Allen 208, 4200-180, Porto, Portugal.

Abstract

The use of synthetic extracellular matrices (ECMs) in fundamental in vitro cell culture studies has been instrumental for investigating the interplay between cells and matrix components. To provide cells with a more native environment in vitro, it is desirable to design matrices that are biomimetic and emulate compositional and structural features of natural ECMs. Here, the supramolecular fabrication of peptide-hyaluronan (HA) hydrogels is presented as potential ECM surrogates, combining native HA and rationally designed cationic amphipatic peptides [(KI)_nK, lysine (K), isoleucine (I), n = 2-6] whose mechanical properties and microstructure are tunable by the peptide sequence. (KI)_nK peptides adopt β-sheet configuration and self-assemble into filamentous nanostructures triggered by pH or ionic strength. The self-assembly propensity of (KI)_nK peptides increases with the sequence length, forming single phase hydrogels (shorter peptides) or with phase separation (longer peptides) in presence of the anionic polyelectrolyte HA through electrostatic complexations. The gel phase formed in (KI)_nK-HA complexes exhibits viscoelastic behavior and triggers the formation of human mesenchymal stem cell (MSC) spheroids which disassemble over the time. It is anticipated that these (KI)_nK-HA hydrogels with tunable physical and biochemical properties offer a promising platform for in vitro applications and in stem cell therapy.

Keywords: Amphipathic peptides; ECM, extracellular matrix; HA, hyaluronan; Hyaluronan; MSC, mesenchymal stem cell; Self-assembly; Stem cell spheroids; Supramolecular structured hydrogels.