Stimuli‑responsive (smart) biomaterials are emerging as versatile platforms for the precision delivery of biotherapeutics. Engineered to sense internal or external cues, these materials undergo reversible physicochemical changes that trigger on‑demand payload release, thus improving efficacy while limiting off‑target toxicity. Here we synthesize the design principles that underpin materials’ selection, architecture, and functionalization and provide a systematic classification of triggering stimuli spanning physical (temperature, light, ultrasound), chemical (pH, redox potential, ionic strength), and biological (enzymes, glucose, reactive oxygen species) cues, including multi‑responsive systems that integrate signals for synergistic control. We describe mechanistic pathways of stimuli transduction and release that enable spatiotemporal dosing. We then survey recent advances in the delivery of small molecules, proteins and peptides, nucleic‑acid therapeutics (DNA, RNA, CRISPR components), vaccines and cells using these platforms, and evaluate their translational potential in targeted therapy and regenerative medicine. Finally, we discuss outstanding challenges, safety, manufacturability, and reproducibility, and outline directions for next‑generation biomaterials capable of intelligent, site‑specific delivery. Stimuli-responsive biomaterials are a versatile platform for the precision delivery of biotherapeutics. This Reviews surveys and discusses the design principles that underpin material selection, architecture, and functionalization, and classifies triggering stimuli.
Singh et al. (2026) studied this question.