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The physiological milieu of healthy skin is slightly acidic, with a pH value between 4 and 6, whereas for skin with chronic or infected wounds, the pH value is above 7.3. As testing pH value is an effective way to monitor the status of wounds, a novel smart hydrogel wound patch incorporating modified pH indicator dyes was developed in this study. Phenol red (PR), the dye molecule, was successfully modified with methacrylate (MA) to allow a copolymerization with the alginate/polyacrylamide (PAAm) hydrogel matrix. This covalent attachment prevented the dye from leaching out of the matrix. The prepared pH-responsive hydrogel patch exhibited a porous internal structure, excellent mechanical property, and high swelling ratio, as well as an appropriate water vapour transmission rate. Mechanical responses of alginate/P(AAm-MAPR) hydrogel patches under different calcium and water contents were also investigated to consider the case of exudate accumulation into hydrogels. Results showed that increased calcium amount and reduced water content significantly improved the Young’s modulus and elongation at break of the hydrogels. These characteristics indicated the suitability of hydrogels as wound dressing materials. When pH increased, the color of the hydrogel patches underwent a transition from yellow (pH 5, 6 and 7) to orange (7.4 and 8), and finally to red (pH 9). This range of color change matches the clinically-meaningful pH range of chronic or infected wounds. Therefore, our developed hydrogels could be applied as promising wound dressing materials to monitor the wound healing process by a simple colorimetric display, thus providing a desirable substrate for printed electronics for smart wound dressing.

Since the last few decades, the development of smart hydrogels, which can respond to stimuli and adapt their responses based on external cues from their environments, has become a thriving research frontier in the biomedical engineering field. Nowadays, drug delivery systems have received great attention and smart hydrogels can be potentially used in these systems due to their high stability, physicochemical properties, and biocompatibility. Smart hydrogels can change their hydrophilicity, swelling ability, physical properties, and molecules permeability, influenced by external stimuli such as pH, temperature, electrical and magnetic fields, light, and the biomolecules’ concentration, thus resulting in the controlled release of the loaded drugs. Herein, this review encompasses the latest investigations in the field of stimuli-responsive drug-loaded hydrogels and our contribution to this matter.

Hydrogels are attractive biomaterials with favorable characteristics due to their water uptake capacity. However, hydrogel properties are determined by the cross-linking degree and nature, the tacticity, and the crystallinity of the polymer. These biomaterials can be sorted out according to the internal structure and by their response to external factors. In this case, the internal interaction can be reversible when the internal chains are led by physicochemical interactions. These physical hydrogels can be synthesized through several techniques such as crystallization, amphiphilic copolymers, charge interactions, hydrogen bonds, stereo-complexing, and protein interactions. In contrast, the internal interaction can be irreversible through covalent cross-linking. Synthesized hydrogels by chemical interactions present a high cross-linking density and are employed using graft copolymerization, reactive functional groups, and enzymatic methods. Moreover, specific smart hydrogels have also been denoted by their external response, pH, temperature, electric, light, and enzyme. This review deeply details the type of hydrogel, either the internal structure or the external response. Furthermore, we detail some of the main applications of these hydrogels in the biomedicine field, such as drug delivery systems, scaffolds for tissue engineering, actuators, biosensors, and many other applications.

In recent years, significant advancements in the field of advanced materials and hydrogel engineering have enabled the design and fabrication of smart hydrogels and nanogels that exhibit sensitivity to specific signals or pathological conditions, leading to a wide range of applications in drug delivery and disease treatment. This comprehensive review aims to provide an in-depth analysis of the stimuli-responsive principles exhibited by smart hydrogels in response to various triggers, such as pH levels, temperature fluctuations, light exposure, redox conditions, or the presence of specific biomolecules. The functionality and performance characteristics of these hydrogels are highly influenced by both their constituent components and fabrication processes. Key design principles, their applications in disease treatments, challenges, and future prospects were also discussed. Overall, this review aims to contribute to the current understanding of gel-based drug delivery systems and stimulate further research in this rapidly evolving field.

Among modern drug formulations, stimuli-responsive hydrogels also called \"smart hydrogels\" deserve a special attention. The basic feature of this system is the ability to change their mechanical properties, swelling ability, hydrophilicity, bioactive molecules permeability, etc., influenced by various stimuli, such as temperature, pH, electromagnetic radiation, magnetic field and biological factors. Therefore, stimuli-responsive matrices can be potentially used in tissue engineering, cell cultures and technology of innovative drug delivery systems (DDSs), releasing the active substances under the control of internal or external stimuli. Moreover, smart hydrogels can be used as injectable DDSs, due to gel-sol transition connected with in situ cross-linking process. Innovative smart hydrogel DDSs can be utilized as matrices for targeted therapy, which enhances the effectiveness of tumor chemotherapy and subsequently limits systemic toxicity. External stimulus sensitivity allows remote control over the drug release profile and gel formation. On the other hand, internal factors provide drg accumulation in tumor tissue and reduce the concentration of active drug form in healthy tissue. In this report, we summarise the basic knowledge and chemical strategies for the synthetic smart hydrogel DDSs applied in antitumor therapy.

Skin is the largest organ of the human body, protecting it against the external environment. Despite high self-regeneration potential, severe skin defects will not heal spontaneously and need to be covered by skin substitutes. Tremendous progress has been made in the field of skin tissue engineering, in recent years, to develop new skin substitutes. Among them, hydrogels are one of the candidates with most potential to mimic the native skin microenvironment, due to their porous and hydrated molecular structure. They can be applied as a permanent or temporary dressing for different wounds to support the regeneration and healing of the injured epidermis, dermis, or both. Based on the material used for their fabrication, hydrogels can be subdivided into two main groups—natural and synthetic. Moreover, hydrogels can be reinforced by incorporating nanoparticles to obtain “in situ” hybrid hydrogels, showing superior properties and tailored functionality. In addition, different sensors can be embedded in hydrogel wound dressings to provide real-time information about the wound environment. This review focuses on the most recent developments in the field of hydrogel-based skin substitutes for skin replacement. In particular, we discuss the synthesis, fabrication, and biomedical application of novel “smart” hydrogels.

The field of regenerative medicine has tremendous potential for improved treatment outcomes and has been stimulated by advances made in bioengineering over the last few decades. The strategies of engineering tissues and assembling functional constructs that are capable of restoring, retaining, and revitalizing lost tissues and organs have impacted the whole spectrum of medicine and health care. Techniques to combine biomimetic materials, cells, and bioactive molecules play a decisive role in promoting the regeneration of damaged tissues or as therapeutic systems. Hydrogels have been used as one of the most common tissue engineering scaffolds over the past two decades due to their ability to maintain a distinct 3D structure, to provide mechanical support for the cells in the engineered tissues, and to simulate the native extracellular matrix. The high water content of hydrogels can provide an ideal environment for cell survival, and structure which mimics the native tissues. Hydrogel systems have been serving as a supportive matrix for cell immobilization and growth factor delivery. This review outlines a brief description of the properties, structure, synthesis and fabrication methods, applications, and future perspectives of smart hydrogels in tissue engineering.

The rapid development of biomedical materials and tissue engineering technology has played an increasingly important role in the process of tissue repair in recent years. Smart‐responsive hydrogels are three‐dimensional network structures formed by cross‐linking of hydrophilic polymers. In addition to having conventional hydrogels that approximate the natural extracellular matrix structure and serve as delivery vehicles for functional molecules (drugs and proteins). More importantly, smart‐responsive hydrogels can achieve relevant changes in material morphology or properties under the conditions of changes in physical, chemical, and biological factors, thereby achieving controlled functional molecules release. It is more urgent to design and build smart‐responsive hydrogels to achieve precise tissue repair with the introduction of the concept of precision medicine and drug delivery. In this review, we highlight different types of smart‐responsive hydrogels and their mechanisms of response to different stimuli and discuss their potential for application in different types of tissue repair, such as chronic wound repair, damaged heart tissue repair, brain nerve tissue repair, and other fields. Finally, we present the prospects of smart‐responsive hydrogels in tissue repair. In general, the current progress in the application of smart‐responsive hydrogels in tissue repair lays the foundation for future applications in other diseases. Smart‐responsive hydrogels can sense the small changes in the surrounding microenvironment and enable precise and controllable release of functional molecules. Smart‐responsive hydrogels with various response mechanisms have attracted extensive attention in the field of tissue repair. We believe that they can be applied in a wider range of fields including but not limited to tissue repair in the future.

Diabetes significantly impairs the body's wound‐healing capabilities, leading to chronic, infection‐prone wounds. These wounds are characterized by hyperglycemia, inflammation, hypoxia, variable pH levels, increased matrix metalloproteinase activity, oxidative stress, and bacterial colonization. These complex conditions complicate effective wound management, prompting the development of advanced diabetic wound care strategies that exploit specific wound characteristics such as acidic pH, high glucose levels, and oxidative stress to trigger controlled drug release, thereby enhancing the therapeutic effects of the dressings. Among the solutions, hydrogels emerge as promising due to their stimuli‐responsive nature, making them highly effective for managing these wounds. The latest advancements in mono/multi‐stimuli‐responsive smart hydrogels showcase their superiority and potential as healthcare materials, as highlighted by relevant case studies. However, traditional wound dressings fall short of meeting the nuanced needs of these wounds, such as adjustable adhesion, easy removal, real‐time wound status monitoring, and dynamic drug release adjustment according to the wound's specific conditions. Responsive hydrogels represent a significant leap forward as advanced dressings proficient in sensing and responding to the wound environment, offering a more targeted approach to diabetic wound treatment. This review highlights recent advancements in smart hydrogels for wound dressing, monitoring, and drug delivery, emphasizing their role in improving diabetic wound healing. It addresses ongoing challenges and future directions, aiming to guide their clinical adoption. This figure illustrates smart hydrogels, persuaded to respond to various stimuli such as temperature, pH, and glucose levels. These smart hydrogels find extensive applications in drug delivery, tissue engineering, and diabetic wound healing due to adapting dynamically to environmental changes.

Hydrogels, as three‐dimensional hydrophilic polymer networks, have been widely utilized in biomedical applications due to their excellent biocompatibility, high water content, and tunable physicochemical properties. However, traditional bulk hydrogels often suffer from limitations such as inadequate mechanical strength, slow response to external stimuli, and restricted diffusion efficiency, which hinder their performance in dynamic biological environments. To overcome these challenges, hydrogel microspheres (HMs) have emerged as a promising alternative, which offers advantages such as injectability, high surface‐area‐to‐volume ratio, and tunable functionality. By integrating natural and synthetic materials with advanced fabrication techniques, including microfluidics and emulsification, researchers have achieved precise control over the morphology, size, and bioactivity of HMs. In recent years, stimuli‐responsive HMs have attracted significant attention for their ability to respond intelligently to environmental cues such as pH, reactive oxygen species (ROS), enzymes, and temperature. This enables controlled drug release, enhanced therapeutic precision, and spatiotemporal regulation in biomedical applications. This review systematically summarizes the materials, fabrication strategies, and functional mechanisms of stimuli‐responsive HMs, highlighting their applications in drug delivery, disease treatment, and tissue engineering. Furthermore, key challenges and future perspectives are discussed, which provides insights into how these intelligent HMs can advance personalized medicine and clinical translation. Hydrogel microspheres (HMs) enhance the properties of traditional hydrogels, offering better injectability and functionality. Advanced fabrication techniques enable precise control over their size and properties. Stimuli‐responsive HMs, which react to pH, ROS, and enzymes, allow targeted drug release and tissue repair. This review discusses their materials, fabrication, and applications, with insights into future clinical potential.