Engineering Smart Hydrogels Through Dynamic Polymer Networks for Controlled Drug Delivery.
5 affiliations
- 1Department of Chemistry and Bioscience, Kumoh National Institute of Technology, 61 Daehak-ro, Gumi 39177, Republic of Korea.
- 2Center for Bio-Healthcare Materials, Bio-Convergence Materials R&D Division, Korea Institute of Ceramic Engineering and Technology, 202 Osongsaengmyeong 1-ro, Osong-eup, Heungdeok-gu, Cheongju 28160, Republic of Korea.
- 3Department of Applied Bioengineering, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 08826, Republic of Korea.
- 4Department of Chemical and Biomolecular Engineering, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea.
- 5Department of Biomedical Engineering, Northwestern University, Evanston, IL 60208, USA.
Abstract
Smart hydrogels are increasingly explored as adaptive platforms for controlled drug delivery because their polymer networks can respond dynamically to chemical, biological, and physical cues. Among these systems, dynamic polymer networks formed through reversible covalent and noncovalent interactions provide a unique means of coupling molecular-scale bond exchange with time-dependent changes in hydrogel structure, mechanics, degradation, and therapeutic transport. This review presents an integrated framework linking dynamic crosslink chemistry, exchange kinetics, network properties, and drug-release behavior. Dynamic covalent, supramolecular, metal-ligand, and hybrid network strategies are compared with particular emphasis on how crosslink lifetime, mesh accessibility, swelling, viscoelasticity, stress relaxation, and degradation govern therapeutic cargo loading, retention, diffusion, and release. Representative release mechanisms and kinetic models are discussed together with cargo-specific design considerations for small molecules, proteins and peptides, nucleic acids, and nanoparticle-based therapeutics. Biomedical applications are further considered according to therapeutic requirements and administration routes, including injectable local depots, topical and transdermal delivery, and regenerative systems. Finally, key translational challenges involving physiological complexity, biocompatibility, reproducibility, scale-up, sterilization, and storage stability are critically assessed. By connecting molecular interaction dynamics with network-level behavior and therapeutic performance, this review provides design principles for developing more predictable, programmable, and clinically translatable dynamic hydrogel drug-delivery systems.
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BibTeX
@article{choi2026engineering,
title = {{Engineering Smart Hydrogels Through Dynamic Polymer Networks for Controlled Drug Delivery.}},
author = {Chanju Choi and Dongseong Seo and Taeho Kim and Jonghyun Park and Dongmin Yu and Sohyeon Yu and Jeongmin Shin and Simseok A Yuk and Daekyung Sung and Hyungjun Kim},
journal = {Gels (Basel, Switzerland)},
year = {2026},
month = sep,
doi = {10.3390/gels12100884},
url = {https://europepmc.org/article/MED/42929917},
note = {CC BY},
}
RIS
TY - JOUR
TI - Engineering Smart Hydrogels Through Dynamic Polymer Networks for Controlled Drug Delivery.
AU - Chanju Choi
AU - Dongseong Seo
AU - Taeho Kim
AU - Jonghyun Park
AU - Dongmin Yu
AU - Sohyeon Yu
AU - Jeongmin Shin
AU - Simseok A Yuk
AU - Daekyung Sung
AU - Hyungjun Kim
PY - 2026
DA - 2026/09/30
JO - Gels (Basel, Switzerland)
DO - 10.3390/gels12100884
UR - https://europepmc.org/article/MED/42929917
AB - Smart hydrogels are increasingly explored as adaptive platforms for controlled drug delivery because their polymer networks can respond dynamically to chemical, biological, and physical cues. Among these systems, dynamic polymer networks formed through reversible covalent and noncovalent interactions provide a unique means of coupling molecular-scale bond exchange with time-dependent changes in hydrogel structure, mechanics, degradation, and therapeutic transport. This review presents an integrated framework linking dynamic crosslink chemistry, exchange kinetics, network properties, and drug-release behavior. Dynamic covalent, supramolecular, metal-ligand, and hybrid network strategies are compared with particular emphasis on how crosslink lifetime, mesh accessibility, swelling, viscoelasticity, stress relaxation, and degradation govern therapeutic cargo loading, retention, diffusion, and release. Representative release mechanisms and kinetic models are discussed together with cargo-specific design considerations for small molecules, proteins and peptides, nucleic acids, and nanoparticle-based therapeutics. Biomedical applications are further considered according to therapeutic requirements and administration routes, including injectable local depots, topical and transdermal delivery, and regenerative systems. Finally, key translational challenges involving physiological complexity, biocompatibility, reproducibility, scale-up, sterilization, and storage stability are critically assessed. By connecting molecular interaction dynamics with network-level behavior and therapeutic performance, this review provides design principles for developing more predictable, programmable, and clinically translatable dynamic hydrogel drug-delivery systems.
SN - 2310-2861
ER -