Controllably degradable β-sheet nanofibers and gels from self-assembling depsipeptides

Area of Science:

• Biomaterials Science
• Polymer Chemistry
• Biotechnology

Background:

• Self-assembled peptide materials are promising for 3D cell culture, tissue engineering, and drug/cell delivery.
• A key limitation is the extreme stability of beta-sheet fibrillized peptides, hindering biological turnover.
• This stability poses challenges for applications requiring material degradation and remodeling.

Purpose of the Study:

• To design and synthesize self-assembling depsipeptides with controlled degradability.
• To investigate the formation and properties of beta-sheet fibrillized nanofibers and hydrogels from these depsipeptides.
• To evaluate the degradation kinetics and biological performance of these novel peptide materials.

Main Methods:

• Design and synthesis of self-assembling depsipeptides incorporating ester bonds.
• Characterization of nanofiber formation and hydrogel properties using HPLC, TEM, and oscillating rheometry.
• Assessment of cell proliferation, spreading, and material softening in 3D cell cultures using C3H10T1/2 pluripotent stem cells.

Main Results:

• Self-assembling beta-sheet fibrillized nanofibers were formed under physiological conditions.
• Two depsipeptide candidates formed hydrogels that degraded controllably over days to weeks via ester hydrolysis.
• Degradation rates were tunable by modifying amino acid residues around the ester bond.
• Depsipeptide gels softened over time in 3D cell cultures, promoting stem cell proliferation and spreading compared to non-degradable analogs.

Conclusions:

• A novel approach using self-assembling depsipeptides offers controlled degradation of beta-sheet fibrillized peptide materials.
• This strategy enables tunable softening and clearance of biomaterials in biological environments.
• These degradable peptide materials show significant potential for advanced applications in regenerative medicine and drug delivery.