AAPS PharmSciTechAug 21, 2025

Hydrogels that respond to signals for targeted antibiotic delivery in bone repair

Regenerative Health Weekly Brief ↗PubMed ↗DOI ↗

Updated Feb 8, 2026

Abstract

Stimuli-responsive hydrogels may enable effective localized antibiotic delivery in bone tissue engineering.

Conventional antibiotic therapies often struggle to provide effective localized concentrations without causing systemic toxicity.
Hydrogels can release antibiotics in response to environmental conditions like pH, temperature, and enzymatic activity.
These smart hydrogels may support bone cell differentiation and improve blood vessel formation.
Different antibiotic delivery mechanisms, including enzyme-sensitive and dual-stimuli systems, have distinct pharmacokinetic advantages and limitations.
Current challenges include ensuring mechanical stability, biocompatibility, and navigating regulatory requirements.

Simplified

Bone tissue engineering (BTE) faces critical challenges in managing infections such as osteomyelitis, which complicate healing and compromise implant success. Conventional antibiotic therapies often fail to achieve effective localized drug concentrations without systemic toxicity. Stimuli-responsive hydrogels have emerged as a transformative solution, offering spatiotemporally controlled, on-demand antibiotic release triggered by environmental cues such as pH, temperature, enzymatic activity, and redox conditions. This review comprehensively analyzes hydrogel classification, design strategies, and their integration within BTE scaffolds. It highlights the synergistic benefits of smart hydrogels in supporting osteogenic differentiation, enhancing vascularization, and combating infection. Key antibiotic delivery mechanisms-from enzyme-sensitive nanocomposites to dual-stimuli systems-are critically examined alongside their pharmacokinetic advantages and limitations. The article also discusses current translational barriers, including mechanical stability, biocompatibility, and regulatory hurdles, while presenting future directions such as biosensing-enabled, 3D-bioprinted, and AI-assisted platforms. Overall, stimuli-responsive hydrogels represent a promising paradigm in precision antibiotic delivery and regenerative bone therapy.

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Declarations: The authors declare that they used AI language tools (ChatGPT and Grammarly Premium) to enhance this manuscript's linguistic clarity and readability. They carefully reviewed and edited all generated text to ensure accuracy and alignment with the research's intended meaning. Conflict of interest: The writers state that they have no known conflicting financial or personal interests that may have impacted the work published in this publication.

PubMed

Hydrogels that respond to signals for targeted antibiotic delivery in bone repair

Abstract

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Funding

Competing interests

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