Search Results (29)

Diabetic wounds remain a major clinical challenge due to impaired angiogenesis, chronic inflammation, oxidative stress, and persistent infection, all of which delay tissue repair. Conventional dressings provide only passive protection and fail to modulate the wound microenvironment effectively. Chitosan (CS) is a naturally derived polysaccharide inspired by biological structures in crustaceans and fungi. It has emerged as a multifunctional biomimetic polymer with excellent biocompatibility, antimicrobial activity, and hemostatic properties. Recent advances in biomimetic materials science have enabled the development of stimuli-responsive CS hydrogels. These systems can sense physiological cues such as pH, temperature, glucose level, light, and reactive oxygen species (ROS). These smart systems emulate natural wound healing mechanisms and adapt to environmental changes. They release bioactive agents on demand and promote tissue homeostasis through controlled angiogenesis and collagen remodeling. This review discusses the biomimetic design rationale, crosslinking mechanism, and emerging strategies underlying single and dual-responsive hydrogel systems. It further emphasizes how nature-inspired structural and functional designs accelerate diabetic wound repair and outlines the current challenges and future prospects for translating these bioinspired intelligent hydrogels into clinical wound care applications. Full article

In this study, succinoglycan (SG), an anionic exopolysaccharide derived from Sinorhizobium meliloti Rm1021, was chemically modified to introduce boronic acid groups, creating a boronic-acid-functionalized polysaccharide (SG-APBA). The degree of substitution varied from 4.24% to 24.3%, depending on APBA concentration, with SG-APBA 2 identified as the optimal formulation. The properties of SG-APBA were characterized using ¹H NMR, FTIR, TGA, and XRD, along with rheological analysis to assess changes in the polymer’s behavior. The hydrogel, referred to as SAT, was formed through dynamic boronate-ester bonds and hydrogen bonds between SG-APBA and tannic acid (TA). This hydrogel demonstrated excellent injectability, self-healing capacity, and biocompatibility. Incorporation of boronic acid groups allowed the hydrogel to respond to variations in glucose levels and pH, enabling controlled TA release and enhancing its stimulus-responsive antioxidant and antibacterial activities. Antioxidant performance was confirmed through DPPH and ABTS radical scavenging assays, achieving respective activities of 89.8% and 96.4%. Antibacterial effectiveness was validated via inhibition zone tests. Additionally, the SAT hydrogel exhibited dual responsiveness to pH and glucose, with TA release percentages of 55.4% at pH 9.0, 62.7% at pH 7.4, and 69.9% at pH 5.0; and 62.7% at 0 mM glucose, 68.9% at 5 mM, and 72.5% at 25 mM glucose after 120 h. Moreover, combined alterations in pH and glucose triggered a synergistic double-shock effect, markedly accelerating TA release relative to individual stimuli. Overall, these results indicate that the SG-APBA/TA hydrogel has strong potential as a stimuli-responsive platform for drug delivery and biomedical applications. Full article

Conductive hydrogels (CHs) have attracted significant attention in the fields of flexible electronics, human–machine interaction, and electronic skin (e-skin) due to their self-adhesiveness, environmental stability, and multi-stimuli responsiveness. However, integrating these diverse functionalities into a single conductive hydrogel system remains a challenge. In this study, polyvinyl alcohol (PVA) and polyacrylamide (PAM) were used as the dual-network matrix, lithium chloride and MXene were added, and a simple immersion strategy was adopted to synthesize a multifunctional MXene-based conductive hydrogel in a glycerol/water (1:1) binary solvent system. A subsequent investigation was then conducted on the hydrogel. The prepared PVA/PAM/LiCl/MXene hydrogel exhibits excellent tensile properties (~1700%), high electrical conductivity (1.6 S/m), and good self-healing ability. Furthermore, it possesses multimodal sensing performance, including humidity sensitivity (sensitivity of −1.09/% RH), temperature responsiveness (heating sensitivity of 2.2 and cooling sensitivity of 1.5), and fast pressure response/recovery times (220 ms/230 ms). In addition, the hydrogel has successfully achieved real-time monitoring of human joint movements (elbow and knee bending) and physiological signals (pulse, breathing), as well as enabled monitoring of spatial pressure distribution via a 3 × 3 sensor array. The performance and versatility of this hydrogel make it a promising candidate for next-generation flexible sensors, which can be applied in the fields of human health monitoring, electronic skin, and human–machine interaction. Full article

Dynamic hydrogels are revolutionizing tumor microenvironment (TME) engineering through their stimuli-responsive adaptability, mechanical tunability, and capacity for multifunctional integration. In addition, they are excellent biomaterials for cancer treatments, including their biomimetic properties and controlled cargo release capability. This review introduces the rational design and principles of dynamic hydrogels for recreating the tumor microenvironment and cancer therapy, including natural/synthetic hydrogels, multi-stimuli responsive hydrogels, and multi-drug loading hydrogels. These designs emphasize their unique roles in overcoming drug resistance, enhancing immunotherapy, and enabling patient-specific models. We highlight breakthroughs such as dual-responsive nanocomposites and microfluidic-integrated 3D platforms while addressing translational hurdles like cytotoxicity and regulatory delays. By proposing strategies to bridge material science with clinical needs, this work positions dynamic hydrogels as pivotal tools for next-generation precision oncology. Full article

Click chemistry has become a powerful and flexible approach for designing hydrogels used in tissue engineering thanks to its high specificity, fast reaction rates, and compatibility with biological systems. In this review, we introduce the core principles of click chemistry, including efficiency, orthogonality, and modularity, and highlight the main types of reactions commonly used in hydrogel formation, such as azide-alkyne c-cloadditions, thiol-ene/yne reactions, Diels–Alder cycloadditions, and tetrazine–norbornene couplings. These chemistries allow researchers to create covalently crosslinked hydrogels that are injectable, responsive to environmental stimuli, biodegradable, or multifunctional. We also explore strategies to enhance bioactivity, such as incorporating peptides, growth factors, or extracellular matrix components, and enabling precise spatial and temporal control over biological cues. Click-based hydrogels have shown promise across a wide range of tissue engineering applications, from cartilage and skin repair to neural regeneration, corneal healing, and cardiovascular scaffolds, as well as in 3D bioprinting technologies. Despite the many advantages of click chemistry such as mild reaction conditions and customizable material properties, some challenges remain, including concerns around copper toxicity, the cost of specialized reagents, and scalability. Finally, we discuss the status of clinical translation, regulatory considerations, and future directions, including integration with advanced bio fabrication methods, the design of dual-click systems, and the emerging role of in vivo click chemistry in creating next-generation biomaterials. Full article

Janus hydrogels have attracted significant attention in materials science and biomedicine owing to their anisotropic dual-faced architecture. Unlike conventional homogeneous hydrogels, these heterogeneous systems exhibit structural and functional asymmetry, endowing them with remarkable adaptability to dynamic environmental stimuli. Their inherent biocompatibility, biodegradability, and unique “adhesion–antiadhesion” duality have demonstrated exceptional potential in biomedical applications ranging from advanced wound healing and internal tissue adhesion prevention to cardiac tissue regeneration. Furthermore, “hydrophilic–hydrophobic” Janus configurations, synergistically integrated with tunable conductivity and stimuli-responsiveness, showcase the great potential in emerging domains, including wearable biosensing, high-efficiency desalination, and humidity regulation systems. This review systematically examines contemporary synthesis strategies for Janus hydrogels using various technologies, including layer-by-layer, self-assembly, and one-pot methods. We elucidate the properties and applications of Janus hydrogels in biomedicine, environmental engineering, and soft robotics, and we emphasize recent developments in this field while projecting future trajectories and challenges. Full article

Heparin-based delivery platforms have gained increasing attention in regenerative medicine due to their exceptional affinity for growth factors and versatility in structural and functional design. This review first introduces the molecular biosynthesis and physicochemical diversity of heparin, which underpin its binding selectivity and degradability. It then categorizes the delivery platforms into microspheres, nanofibers, and hydrogels, with detailed discussions on their fabrication techniques, biofunctional integration of heparin, and release kinetics. Special focus is given to stimuli-responsive systems—including pH-, enzyme-, redox-, thermal-, and ultrasound-sensitive designs—which allow spatiotemporal control over growth factor release. The platform applications are organized by tissue types, encompassing soft tissue regeneration, bone and cartilage repair, neuroregeneration, cardiovascular regeneration, wound healing, anti-fibrotic therapies, and cancer microenvironment modulation. Each section provides recent case studies demonstrating how heparin enhances the bioactivity, localization, and therapeutic efficacy of pro-regenerative or anti-pathologic growth factors. Collectively, these insights highlight heparin’s dual role as both a carrier and modulator, positioning it as a pivotal component in next-generation, precision-targeted delivery systems. Full article

The development of multifunctional conductive hydrogels with rapid self-healing capabilities and powerful sensing functions is crucial for advancing wearable electronics. This study designed and prepared a polyvinyl alcohol (PVA)–borax hydrogel incorporating carbon nanotubes (CNTs) and biomass carbon nanospheres (CNPs) as dual-carbon fillers. This hydrogel exhibits excellent conductivity, mechanical flexibility, and self-recovery properties. Serving as a highly sensitive piezoresistive sensor, it efficiently converts mechanical stimuli into reliable electrical signals. Sensing tests demonstrate that the CNT/CNP/PVA–borax hydrogel sensor possesses an extremely fast response time (88 ms) and rapid recovery time (88 ms), enabling the detection of subtle and rapid human motions. Furthermore, the hydrogel sensor also exhibits outstanding cyclic stability, maintaining stable signal output throughout continuous loading–unloading cycles exceeding 3200 repetitions. The hydrogel sensor’s characteristics, including rapid self-healing, fast-sensing response/recovery, and high fatigue resistance, make the CNT/CNP/PVA–borax conductive hydrogel an ideal choice for multifunctional wearable sensors. It successfully monitored various human motions. This study provides a promising strategy for high-performance self-healing sensing devices, suitable for next-generation wearable health monitoring and human–machine interaction systems. Full article

Conventional drug delivery approaches, including tablets and capsules, often suffer from reduced therapeutic effectiveness, largely attributed to inadequate bioavailability and difficulties in ensuring patient adherence. These challenges have driven the development of advanced drug delivery systems (DDS), with hydrogels and especially nanogels emerging as promising materials to overcome these limitations. Hydrogels, with their biocompatibility, high water content, and stimuli-responsive properties, provide controlled and targeted drug release. This review explores the evolution, properties, and classifications of hydrogels versus nanogels and their applications in drug delivery, detailing synthesis methods, including chemical crosslinking, physical self-assembly, and advanced techniques such as microfluidics and 3D printing. It also examines drug-loading mechanisms (e.g., physical encapsulation and electrostatic interactions) and release strategies (e.g., diffusion, stimuli-responsive, and enzyme-triggered). These gels demonstrate significant advantages in addressing the limitations of traditional DDS, offering improved drug stability, sustained release, and high specificity. Their adaptability extends to various routes of administration, including topical, oral, and injectable forms, while emerging nanogels further enhance therapeutic targeting through nanoscale precision and stimuli responsiveness. Although hydrogels and nanogels have transformative potential in personalized medicine, challenges remain in scalable manufacturing, regulatory approval, and targeted delivery. Future strategies include integrating biosensors for real-time monitoring, developing dual-stimuli-responsive systems, and optimizing surface functionalization for specificity. These advancements aim to establish hydrogels and nanogels as cornerstones of next-generation therapeutic solutions, revolutionizing drug delivery, and paving the way for innovative, patient-centered treatments. Full article

An imbalance in the body’s pH or temperature may modify the immune response and result in ailments such as autoimmune disorders, infectious diseases, cancer, or diabetes. Dual pH- and thermo-responsive carriers are being evaluated as advanced drug delivery microdevices designed to release pharmaceuticals in response to external or internal stimuli. A novel drug delivery system formulated as hydrogel was developed by combining a pH-sensitive polymer (the “biosensor”) with a thermosensitive polymer (the delivery component). Thus, the hydrogel was created by cross-linking, using a solvent-free thermal approach, of poly(N-isopropylacrylamide-co-N-hydroyethyl acrylamide), P(NIPAAm-co-HEAAm), and poly(methylvinylether-alt-maleic acid), P(MVE/MA). The chemical structure of the polymers and hydrogels was analyzed using Fourier-transform infrared (FTIR) and proton nuclear magnetic resonance (¹H NMR) spectroscopies. The pH/thermosensitive hydrogel loses its thermosensitivity under physiological conditions but, remarkably, can recover the thermosensitive capabilities when certain physiologically active biomolecules, acting as triggering agents, electrostatically interact with pH-sensitive units. Our research aimed to develop a drug delivery system that could identify the disturbance of normal physiological parameters and instantaneously send a signal to thermosensitive units, which would collapse and modulate the release profiles of the drug. Full article

Smart materials for drug delivery are designed to offer a precise and controlled release of therapeutic agents. By responding to specific physiological stimuli, such as changes in temperature and pH, these materials improve treatment efficacy and minimize side effects, paving the way for personalized therapeutic solutions. In this study, we present the fabrication of dual-responsive alginate/poly(N-isopropylacrylamide) (PNIPAM) microspheres, having the ability to respond to both pH and temperature variations and embedding the lipophilic bioactive compound Ozoile. Ozoile^® Stable Ozonides is obtained from extra virgin olive oil and acts as an inducer, interacting with major biological pathways by means of modulating the systemic redox balance. The dual-responsive microspheres are prepared by electrospray technique without the use of organic solvents. PNIPAM is synthesized by radical polymerization using the APS/TEMED redox initiators. The microspheres are further optimized with a chitosan coating to enhance their stability and modulate the degradation kinetics of the gel matrix. A comprehensive morphological analysis, Fourier transform infrared (FTIR) spectroscopy, and degradation assays are conducted to confirm the structural stability and pH-responsive behavior of the hydrogel microspheres. A study of the volume phase transition temperature (VPTT) by differential scanning calorimetry (DSC) is used to assess the microsphere thermal response. This research introduces a promising methodology for the development of targeted drug delivery systems, which are particularly useful in the context of oxidative stress modulation and inflammation management. Full article

Despite advancements in early detection and treatment in developed countries, colorectal cancer (CRC) remains the third most common malignancy and the second-leading cause of cancer-related deaths worldwide. Conventional chemotherapy, a key option for CRC treatment, has several drawbacks, including poor selectivity and the development of multiple drug resistance, which often lead to severe side effects. In recent years, the use of polysaccharides as drug delivery systems (DDSs) to enhance drug efficacy has gained significant attention. Among these polysaccharides, chitosan (CS), a linear, mucoadhesive polymer, has shown promise in cancer treatment. This review summarizes current research on the potential applications of CS-based hydrogels as DDSs for CRC treatment, with a particular focus on smart hydrogels. These smart CS-based hydrogel systems are categorized into two main types: stimuli-responsive injectable hydrogels that undergo sol-gel transitions in situ, and single-, dual-, and multi-stimuli-responsive CS-based hydrogels capable of releasing drugs in response to various triggers. The review also discusses the structural characteristics of CS, the methods for preparing CS-based hydrogels, and recent scientific advances in smart CS-based hydrogels for CRC treatment. Full article

Cancer is a highly heterogeneous disease and remains a global health challenge affecting millions of human lives worldwide. Despite advancements in conventional treatments like surgery, chemotherapy, and immunotherapy, the rise of multidrug resistance, tumor recurrence, and their severe side effects and the complex nature of the tumor microenvironment (TME) necessitates innovative therapeutic approaches. Recently, stimulus-responsive nanomedicines designed to target TME characteristics (e.g., pH alterations, redox conditions, enzyme secretion) have gained attention for their potential to enhance anticancer efficacy while minimizing the adverse effects of chemotherapeutics/bioactive compounds. Among the various nanocarriers, hydrogels are intriguing due to their high-water content, adjustable mechanical characteristics, and responsiveness to external and internal stimuli, making them promising candidates for cancer therapy. These properties make hydrogels an ideal nanocarrier for controlled drug release within the TME. This review comprehensively surveys the latest advancements in the area of stimulus-responsive hydrogels for cancer therapy, exploring various stimuli-responsive mechanisms, including biological (e.g., pH, redox), chemical (e.g., enzymes, glucose), and physical (e.g., temperature, light), as well as dual- or multi-stimuli responsiveness. Furthermore, this review addresses the current developments and challenges in hydrogels in cancer treatment. Our aim is to provide readers with a comprehensive understanding of stimulus-responsive hydrogels for cancer treatment, offering novel perspectives on their development for cancer therapy and other medical applications. Full article

The regulated and targeted administration of hydrophobic and hydrophilic drugs is both promising and challenging in the field of drug delivery. Developing a hydrogel which is responsive to dual stimuli is considered a promising and exciting research area of study. In this work, melamine functionalized poly-N-isopropyl acrylamide-co-glycidyl methacrylate copolymer has been developed by copolymerizing glycidyl methacrylate (GMA) monomer with N-isopropyl acrylamide (NIPAm) and further functionalized with melamine units (pNIPAm-co-pGMA-Mela). The prepared pNIPAm-co-pGMA-Mela copolymer hydrogel was characterized using various characterization techniques, including ¹H NMR, FTIR, SEM, zeta potential, and particle size analysis. A hydrophobic drug (ibuprofen, Ibu) and hydrophilic drug (5-fluorouracil, 5-Fu) were selected as model drugs. Dual pH and temperature stimuli-responsive drug release behavior of the pNIPAm-co-pGMA-Mela hydrogel was evaluated under different pH (pH 7.4 and 4.0) and temperature (25 °C, 37 °C, and 45 °C) conditions. Furthermore, the in vitro biocompatibility of the developed pNIPAm-co-pGMA-Mela copolymer hydrogel was determined on MDA-MB-231 cells. The pH and temperature-responsive drug delivery study results reveal that the pNIPAm-co-pGMA-Mela hydrogel system is responsive to both pH and temperature stimuli and exhibits about ~100% of Ibu and 5-Fu, respectively, released at pH 4.0/45 °C. Moreover, the MTT assay and hemocompatibility analysis results proved that the pNIPAm-co-pGMA-Mela hydrogel system is biocompatible and hemocompatible, suggesting that that it could be used for drug delivery applications. The experimental results suggest that the proposed pNIPAm-co-pGMA-Mela hydrogel system is responsive to dual pH and temperature stimuli, and could be a promising drug carrier system for both hydrophilic and hydrophobic drug delivery applications. Full article

The development of dual-stimuli-responsive hydrogels attracts much research interest owing to its unique stimuli-responsive characteristics. In this study, a poly-N-isopropyl acrylamide-co-glycidyl methacrylate-based copolymer was synthesized by incorporating N-isopropyl acrylamide (NIPAm) and a glycidyl methacrylate (GMA) monomer. The synthesized copolymer, pNIPAm-co-GMA was further modified with L-lysine (Lys) functional units and further conjugated with fluorescent isothiocyanate (FITC) to produce a fluorescent copolymer pNIPAAm-co-GMA-Lys hydrogel (HG). The in vitro drug loading and dual pH- and temperature-stimuli-responsive drug release behavior of the pNIPAAm-co-GMA-Lys HG was investigated at different pH (pH 7.4, 6.2, and 4.0) and temperature (25 °C, 37 °C, and 45 °C) conditions, respectively, using curcumin (Cur) as a model anticancer drug. The Cur drug-loaded pNIPAAm-co-GMA-Lys/Cur HG showed a relatively slow drug release behavior at a physiological pH (pH 7.4) and low temperature (25 °C) condition, whereas enhanced drug release was achieved at acidic pH (pH 6.2 and 4.0) and higher temperature (37 °C and 45 °C) conditions. Furthermore, the in vitro biocompatibility and intracellular fluorescence imaging were examined using the MDA-MB-231 cell line. Therefore, we demonstrate that the synthesized pNIPAAm-co-GMA-Lys HG system with temperature- and pH-stimuli-responsive features could be promising for various applications in biomedical fields, including drug delivery, gene delivery, tissue engineering, diagnosis, antibacterial/antifouling material, and implantable devices. Full article