Microbiome-Responsive Hydrogels: From Biological Cues to Smart Biomaterials

Authors

• Rajesh Vadlapatla, Marshall B. Ketchum University
• Amir Nasrolahi Shirazi, Marshall B. Ketchum UniversityFollow
• Ajoy Koomer, Marshall B. Ketchum University
• Judy Weng, Marshall B. Ketchum University
• Matthew Ernest Ghilarducci, Marshall B. Ketchum University
• Alai Qudus, Marshall B. Ketchum University
• Keykavous Parang, Chapman UniversityFollow

Document Type

Article

Publication Date

2-24-2026

Abstract

Background: Stimuli-responsive hydrogels (SRHs) are smart polymeric materials that undergo reversible physicochemical changes in response to abiotic cues and externally applied fields, enabling applications in drug delivery, wound healing, and tissue engineering. However, they exhibit limited biological specificity and do not adequately reflect the dynamic, disease-relevant complexity of native tissue microenvironments. Microbe-colonized tissues display distinctive biochemical features driven, shaped by microbial metabolism, including localized pH gradients, short-chain fatty acid production, secretion of quorum-sensing molecules, biofilm formation, and expression of specialized enzymes. These endogenous, spatiotemporally regulated signals are closely linked to host physiology and pathology but remain underutilized in hydrogel design. This review aims to highlight microbiome-responsive hydrogels (MRHs) as a strategy to address this gap. Methods: This study summarizes current engineering approaches, key microbial stimuli, and emerging biomedical applications of MRHs, with emphasis on translational and regulatory challenges. Results: Microbiome-responsive hydrogels (MRHs) address this gap by leveraging microbial metabolic and biochemical cues to induce swelling, degradation, drug release, antibacterial activity, or structural transformation. By directly coupling to microbe-derived stimuli, MRHs offer improved physiological relevance, enhanced local specificity, and new opportunities for precision therapy targeting disease-associated microbial niches. Conclusions: Despite their promise, MRHs remain an early and fragmented field, lacking standardized biological triggers, material design frameworks, and performance evaluation strategies. This review summarizes current engineering approaches, key microbial stimuli, and emerging biomedical applications, with emphasis on translational and regulatory challenges, positioning MRHs as an underexplored platform for next-generation smart biomaterials.

Comments

This article was originally published in Pharmaceutics, volume 18, issue 3, in 2026. https://doi.org/10.3390/pharmaceutics18030284

Recommended Citation

Vadlapatla, R.; Shirazi, A.N.; Koomer, A.; Weng, J.; Ghilarducci, M.E.; Qudus, A.; Parang, K. Microbiome-Responsive Hydrogels: From Biological Cues to Smart Biomaterials. Pharmaceutics 2026, 18, 284. https://doi.org/10.3390/pharmaceutics18030284

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This work is licensed under a Creative Commons Attribution 4.0 License.