Tuning hydrogel properties with sequence-defined, non-natural peptoid crosslinkers

• Published in: Journal of materials chemistry. B, Materials for biology and medicine Vol. 8; no. 31; pp. 6925 - 6933
• Main Authors: Morton, Logan D, Hillsley, Alexander, Austin, Mariah J, Rosales, Adrianne M
• Format: Journal Article
• Language: English
• Published: England Royal Society of Chemistry 21.08.2020
• Subjects: Amino Acid Sequence; Biological activity; Biopolymers; Bulk modulus; Cell culture; Cell Survival - drug effects; Chains; Crosslinking; Extracellular matrix; Fibroblasts; Fibroblasts - cytology; Fibroblasts - drug effects; Humans; Hydrogels; Hydrogels - chemistry; Microenvironments; Peptides; Peptides - chemistry; Peptides - pharmacology; Polyethylene glycol; Polyethylene Glycols - chemistry; Protein Conformation, alpha-Helical; Storage modulus; Structural hierarchy; Substitutes; Tissue engineering
• ISSN: 2050-750X; 2050-7518
• DOI: 10.1039/d0tb00683a

The native extracellular matrix (ECM) is composed of hierarchically structured biopolymers containing precise monomer sequences and chain shapes to yield bioactivity. Recapitulating this structure in synthetic hydrogels is of particular interest for tissue engineering and in vitro disease models to accurately mimic biological microenvironments. However, despite extensive research on hydrogels, it remains a challenge to recapitulate the hierarchical structure of native ECM with completely synthetic hydrogel platforms. Toward this end, this work presents a synthetic hydrogel system using commercially available poly(ethylene glycol) macromers with sequence-defined poly( N -substituted glycines) (peptoids) as crosslinkers. We demonstrate that bulk hydrogel mechanics, specifically as shear storage modulus, can be controlled by altering peptoid sequence and structure. Notably, the helical peptoid sequence investigated here increases the storage modulus of the resulting hydrogels with increasing helical content and chain length, in a fashion similar to helical peptide-crosslinked hydrogels. In addition, the resulting hydrogels are shown to be hydrolytically and enzymatically stable due to the N -substituted peptidomimetic backbone of the crosslinkers. We further demonstrate the potential utility of these peptoid-crosslinked hydrogels as a viable cell culture platform using seeded human dermal fibroblasts in comparison to peptide-crosslinked hydrogels as a control. Taken together, our system offers a strategy toward ECM mimics that replicate the hierarchy of biological matrices with completely synthetic, sequence-defined molecules. Helical peptoid crosslinkers confer tunable mechanical properties and enzymatic stability to hydrogels for cell culture.