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Tuning hydrogel properties with sequence-defined, non-natural peptoid crosslinkers
Logan D Morton1, Alexander Hillsley, Mariah J Austin
1McKetta Department of Chemical Engineering, University of Texas at Austin, Austin, TX, USA. arosales@che.utexas.edu.
Journal of Materials Chemistry. B
|May 22, 2020
Summary
This study introduces synthetic hydrogels using sequence-defined peptoids to mimic the extracellular matrix (ECM). These peptoid-crosslinked hydrogels offer tunable mechanics and stability for tissue engineering applications.
Area of Science:
- Biomaterials Science
- Tissue Engineering
- Polymer Chemistry
Background:
- The native extracellular matrix (ECM) possesses hierarchical structures crucial for biological functions.
- Mimicking native ECM in synthetic hydrogels is vital for advanced tissue engineering and in vitro models.
- Current synthetic hydrogels struggle to replicate the complex hierarchical structure of native ECM.
Purpose of the Study:
- To develop a completely synthetic hydrogel system capable of recapitulating ECM hierarchy.
- To utilize sequence-defined peptoids as crosslinkers for precise control over hydrogel properties.
- To investigate the mechanical properties, stability, and cell culture potential of these novel hydrogels.
Main Methods:
- Synthesized hydrogels using poly(ethylene glycol) macromers and sequence-defined peptoids as crosslinkers.
- Characterized bulk hydrogel mechanics (shear storage modulus) by varying peptoid sequence and structure.
- Assessed hydrogel stability (hydrolytic and enzymatic) and evaluated cell culture performance with human dermal fibroblasts.
Main Results:
- Hydrogel mechanics, specifically shear storage modulus, were effectively controlled by altering peptoid sequence and structure.
- Helical peptoid sequences increased storage modulus with higher helical content and chain length, mirroring peptide behavior.
- The resulting peptoid-crosslinked hydrogels exhibited significant hydrolytic and enzymatic stability.
- Peptoid-crosslinked hydrogels demonstrated viability as a cell culture platform, comparable to peptide controls.
Conclusions:
- Developed a synthetic hydrogel system using sequence-defined peptoids that successfully mimics native ECM hierarchy.
- Demonstrated tunable mechanical properties and enhanced stability in these novel biomaterials.
- Presented a promising strategy for creating advanced ECM mimics for tissue engineering and disease modeling.

