De novo design of alpha-helical peptide amphiphiles repairing fragmented collagen type I via supramolecular co-assembly

TL;DR

This study introduces a minimal alpha-helical peptide amphiphile that self-assembles to recognize and repair fragmented collagen, enabling improved tissue regeneration through supramolecular co-assembly.

Contribution

A novel de novo-designed peptide amphiphile that selectively restores collagen structure and guides tissue repair via supramolecular assembly.

Findings

Restores collagen triple-helix conformation

Enables spatial control in 3D printing of biomaterials

Enhances tissue regeneration in a porcine model

Abstract

The hierarchical triple-helix structure of collagen type I, Col I, is essential for extracellular matrix support and integrity. However, current reconstruction strategies face challenges such as chain mismatch, preventing proper fibril formation. Here, we report a supramolecular co-assembly strategy using a de novo-designed alpha-helical peptide amphiphile (APA) of just seven amino acids. The APA features a hydrophobic palmitic acid tail, which stabilizes the helical structure and promotes co-assembly upon interaction with complementary molecular structures. This minimal design enables selective recognition of fragmented collagen (FC), restoring triple-helix conformation and guiding fibre formation. We applied this mechanism to engineer FC-rich nanofat (NF) into a mechanically reinforced biomaterial. Integration of APA-NF with coaxial 3D printing enabled spatial control of structure and function. In a porcine model, this platform enhanced in situ vascularized adipose tissue regeneration. Our results demonstrate that hierarchical reconstruction of collagen via peptide-guided supramolecular assembly offers a promising strategy for soft tissue repair.