Structure- or size-transformable peptide-based antibacterial biomaterials: Design strategies, functions, and applications.

Chen, Zhenduo; Zhao, Guanghui; Qu, Yuankai; Tang, Qi; Yang, Shuaikang; Zhou, Chenlong; Li, Mingtan; Kang, Yunlu et al. · Acta Biomater · 2025

review · Level V

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Abstract

Bacterial infections have emerged as a significant challenge to global public health. However, traditional antibiotics often fall short in meeting the clinical demands for infection treatment due to their considerable side effects, poor targeting ability, limited antibacterial spectrum, and unfavorable pharmacokinetics. This situation underscores the urgent need for alternative strategies in the field of infection research. Structure- or size-transformable peptide-based antibacterial biomaterials (SSTPABs) can be designed to flexibly respond to endogenous pathological features within the bacterial infection microenvironment (pH, enzymes, reactive oxygen species , etc.), as well as external stimuli (light, ultrasound, etc.). These biomaterials exhibit varied properties through size transformations, enabling them to meet diverse application requirements. This review begins with an overview of various types of SSTPABs, detailing their transformation from monomers to nanostructures (nanoparticles, nanofibers, etc.), from nanostructures back to monomers, between identical nanostructures, and between different nanostructures (nanosheets, nanorods, etc.). Additionally, the design strategies employed for SSTPABs are summarized. Subsequently, within the context of bacterial infection treatment, we elaborate on four key functions of SSTPABs: enhancing biofilm penetration efficiency, improving accumulation and retention at the infection site, controlling drug release, and achieving bacteria-specific capture. Finally, we outline the primary challenges faced by SSTPABs in clinical translation and provide references for future research directions aimed at fostering the innovation and application of peptide-based antibacterial biomaterials in the fields of animal husbandry, materials science, and biomedicine. STATEMENT OF SIGNIFICANCE: Structure- or size-transformable peptide-based antibacterial biomaterials (SSTPABs) can be flexibly designed to respond to endogenous pathological features within the bacterial infection microenvironment as well as external stimuli. They exhibit varied properties through size transformations to meet diverse application requirements. This review emphasizes the design strategies of various types of STPABs, with a particular focus on their four key functions: biofilm penetration, accumulation and retention at the infection site, controlled drug release, and bacteria-specific capture. Furthermore, this review provides a comprehensive overview of the structure-function relationship of STPABs, thereby fostering innovation and application of peptide-based antibacterial biomaterials across animal husbandry, nanotechnology, and biomedical fields. The studies covered span from 2020 to the present.

Medical subject headings