Programming angiogenesis with tunable assemblies of multifunctional peptides

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Molecular Engineering

Background:

• Therapeutic angiogenesis is limited by challenges in controlling vascular signaling.
• Existing methods struggle with localization, sustained release, and precise tuning of angiogenic factors.

Purpose of the Study:

• To engineer a supramolecular peptide system for precise angiogenic programming.
• To decouple mechanical properties from bioactivity for enhanced control over vascular signaling.

Main Methods:

• Integration of a VEGF-mimetic amphiphile (SLan) with a robust beta-sheet peptide (K1).
• Creation of injectable nanofiber hydrogels with tunable stiffness (100-1000 Pa).
• Utilized molecular dynamics simulations and solid-state NMR to analyze coassembly and receptor interactions.

Main Results:

• The SLan-K1 hydrogels exhibited tunable stiffness while maintaining VEGFR2 affinity.
• Coassembly mitigated steric hindrance, allowing dense packing and optimal receptor accessibility.
• The formulation activated the VEGFR2-MEK-ERK pathway, inducing endothelial proliferation in vitro and neovascularization in vivo.

Conclusions:

• The peptide system enables precise control over angiogenic programming by decoupling mechanics and bioactivity.
• This modular platform facilitates the engineering of instructive microenvironments for tissue regeneration.
• The study provides a molecular framework for developing tunable angiogenic materials bridging molecular design and tissue function.