Smart hydrogels for in situ tissue drug delivery

Abstract

The application of smart hydrogels has become a booming research frontier in biomedical engineering. With the development of intelligent drug delivery systems, various biomimetic and biodegradable hydrogels are employed for localized drug delivery to tissues in the preclinical applications. These advanced materials are designed to match the diverse environmental and functional requirements of various tissue types and organs. This article discusses the attractive characteristics of smart hydrogels as delivery systems and reviews the design of a range of smart hydrogels, as well as the challenges of tissue-specific drug delivery, focusing on the last 5 years of frontward research.

Keywords: Controlled release; Drug delivery; Hydrogels; Smart hydrogels.

Fig. 1

Chemistry and mechanisms for rational design of drug delivery hydrogel and biomedical applications

Fig. 2

Illustration of smart hydrogels designed for controlled drug release. A Photo-responsive and dynamic-covalent hydrogel featuring NIR-triggered drug delivery for photothermal combination therapy. [36] (Copyright 2020 American Chemical Society) B pH-responsive hydrogel loaded with insulin as a bioactive dressing to improve diabetic wound healing. [37] (Copyright 2021 Elsevier) C Thermo-responsive hydrogel induced by dual supramolecular assemblies and its controlled release property for enhanced delivery of anticancer drugs. [38] (Copyright 2020 American Chemical Society) D Glucose-sensitive hydrogels derived from covalently modified carboxylated pullulan and concanavalin A for intelligent controlled release of insulin. [39] (Copyright 2019 Elsevier) E A dual dynamic covalent bond hydrogel based on carboxymethyl chitosan with enhanced mechanical properties, high drug encapsulation efficiency, and sustained release properties. [40] (Copyright 2023 Elsevier)

Fig. 3

The schematic diagram of drug-loaded smart hydrogels applied to various tissues, organs, and systems. The blue markers indicate the hydrogel properties that are required for application to that tissue

Fig. 4

Studies of smart hydrogel systems for in situ drug delivery applications. A Self-healing and hierarchical hydrogel for asynchronous delivery targeting intracerebral hemorrhage stroke rats. [34] (Copyright 2023 Wiley) B Self-healing adhesive hydrogel shows sustained release of magnesium ions and promotes chondrogenic differentiation for fibrocartilaginous interface regeneration in the rabbit rotator cuff tear model. [48] (Copyright 2020 Elsevier) C pH- and ROS-responsive hydrogel with sympatho-immune regulation and cardiac remodeling properties for treating rat myocardial infarction. [51] (Copyright 2025 Elsevier) D Self-healed trilayer cryogel with tunable pore sizes and Y27632/dexamethasone releasing ability for rabbit osteochondral regeneration. [49] (Copyright 2024 Wiley) E Sono-responsive hydrogel enabling high tissue penetration and anti-tumor immunotherapy. [53] (Copyright 2024 Wiley)