# β-Hairpin-Based Peptide Hydrogels: The Case of MAX1

## TL;DR

This review discusses β-hairpin peptide hydrogels, focusing on MAX1 and its variants, and their potential for tissue engineering and drug delivery.

## Contribution

The paper provides a comprehensive review of β-hairpin-based hydrogels, emphasizing MAX1 and its engineered analogues for tunable biomaterials.

## Key findings

- MAX1 forms a self-supporting gel under physiological conditions, suitable for injectable therapies.
- Engineered MAX1 analogues show varied gelation kinetics and mechanical properties.
- β-hairpin hydrogels are categorized into five groups for tailored biomedical applications.

## Abstract

This review explores the advancements and applications of β-hairpin peptide hydrogels, starting from the paradigmatic case of MAX1 and its highly versatile analogue MAX8. MAX1 (H-VKVKVKVKVDPPTKVKVKVKV-NH2) has been identified as the first synthetic β-hairpin peptide for the preparation of stimuli-responsive peptide-based hydrogels. At low ionic strength or neutral pH, MAX1 remains unfolded and soluble. However, under physiological conditions, it folds into a β-hairpin structure, then producing a self-supporting matrix within minutes. The formed gel is shear-thinning and self-healing, making it suitable for injectable therapies. To explore MAX1 molecular space and enhance its practical clinical use, the primary sequence was engineered via chemical modification, with specific single amino acid substitution and relative net charge alteration. This approach generates MAX1 analogues, differing in gelation kinetics, mechanical response and biological performances. The β-hairpin peptide hydrogels are categorized into five different groups: MAX1, MAX1 analogues, MAX8, MAX8 analogues and non-MAX peptides sequences. Collectively, the review outcomes demonstrate the use of β-hairpin peptide matrices as tunable platforms for the development of predictable and stable biomaterials for advanced tissue engineering and drug delivery applications.