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20 pages, 7513 KB  
Article
Combined Stromal Vascular Fraction and HGF-Functionalized Self-Assembling Peptide Hydrogel Improves Intracerebral Hemorrhage Repair in Rats
by Xuhuai Chen, Tiantian Li, Feng Yang, Yanling Chen, Yuanyi Liu, Linshu Ding, Jialin Li, Haibo Zhou, Qiuju Yuan and Wutian Wu
Gels 2026, 12(3), 257; https://doi.org/10.3390/gels12030257 - 19 Mar 2026
Abstract
Intracerebral hemorrhage (ICH) remains a devastating condition with no available therapies that can effectively mitigate secondary injury and promote neurological repair. This research presents a novel combinatorial regenerative strategy, concurrently delivering adipose-derived stromal vascular fraction (SVF) within an adhesive self-assembling peptide (HGF-RADA16-IKVAV) nanohydrogel [...] Read more.
Intracerebral hemorrhage (ICH) remains a devastating condition with no available therapies that can effectively mitigate secondary injury and promote neurological repair. This research presents a novel combinatorial regenerative strategy, concurrently delivering adipose-derived stromal vascular fraction (SVF) within an adhesive self-assembling peptide (HGF-RADA16-IKVAV) nanohydrogel (HGF). In a clinically relevant rat model of ICH with hematoma evacuation, the combined therapy of HGF and SVF demonstrated synergistic and enhanced efficacy. In the short term, the combined therapy demonstrated hemostatic benefits, and significantly reduced hematoma volume, brain edema, neuronal apoptosis and neuroinflammation indicated by pro-inflammatory markers (NLRP3, caspase-1, Iba-1, CD68, GFAP) while increasing the levels of anti-inflammatory (CD206) and angiogenic (CD31) markers. Longitudinal behavioral assessments conducted over six weeks demonstrated persistent and significant improvements in motor coordination, forelimb strength, and gait parameters within the HGF + SVF group, surpassing all monotherapies. Ultrastructural analysis also showed that myelinated axons were better preserved at the injury border, with thicker myelin sheaths. These findings demonstrate that the co-administration of SVF with an adhesive and hemostatic hydrogel collaboratively diminishes secondary injury, modulates neuroinflammation, and promotes functional and structural brain recovery following ICH, indicating a promising and translatable strategy. Full article
(This article belongs to the Section Gel Analysis and Characterization)
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32 pages, 1957 KB  
Review
Chronic Wound Healing: Research Advances from Pathological Mechanisms to Natural Herbal Active Ingredients and Material Delivery Systems
by Mengqing Yuan, Yufeng Liu, Xiaoyin Peng, Zhenjun Li and Mingsheng Lei
Molecules 2026, 31(6), 1024; https://doi.org/10.3390/molecules31061024 - 19 Mar 2026
Abstract
Chronic wound healing is a complex pathological process driven by multiple factors, presenting a significant global healthcare challenge. It not only severely compromises patients’ quality of life but also imposes a substantial socioeconomic burden. In recent years, with deepening insights into the wound [...] Read more.
Chronic wound healing is a complex pathological process driven by multiple factors, presenting a significant global healthcare challenge. It not only severely compromises patients’ quality of life but also imposes a substantial socioeconomic burden. In recent years, with deepening insights into the wound microenvironment, composite therapeutic strategies combining natural herbal medicines and their active components with modern biomaterials have offered novel approaches to overcoming refractory wounds caused by diabetic ulcers, vascular lesions, burns, and infections. This paper first outlines the biological foundations of normal wound healing, emphasizing the core mechanisms underlying chronic wound persistence—including persistent inflammatory responses, impaired tissue repair, and cellular dysfunction. Building upon this foundation, the article systematically reviews the existing therapeutic approaches (such as conventional debridement) before focusing on the classification and application of novel biomaterials. It further analyzes the synergistic therapeutic advantages of using materials as delivery systems for natural bioactive compounds. This combined approach enables targeted regulation of the chronic wound microenvironment, synergistically promoting cell proliferation and migration to accelerate healing. Deepening our understanding of the biological mechanisms underlying chronic wounds, coupled with advanced biomaterial technologies, will propel clinical treatment toward more precise and efficient outcomes. Full article
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24 pages, 2789 KB  
Article
Formulation and Characterization of Edible Bigel Inks for Structuring Fat Alternatives in 3D-Printed Foods
by Konstantina Zampouni, Theocharis Salamandrakis, Triantafyllia Biza, Thomas Moschakis and Eugenios Katsanidis
Gels 2026, 12(3), 254; https://doi.org/10.3390/gels12030254 - 18 Mar 2026
Viewed by 52
Abstract
Bigels (BGs) are promising biphasic systems for extrusion-based 3D food printing inks. In this study, BG inks were formulated by combining a 6% beeswax—4% monoglycerides oleogel (OG) with a 4% gelatin—1% guar gum hydrogel (HG). The BGs were formulated at OG:HG ratios of [...] Read more.
Bigels (BGs) are promising biphasic systems for extrusion-based 3D food printing inks. In this study, BG inks were formulated by combining a 6% beeswax—4% monoglycerides oleogel (OG) with a 4% gelatin—1% guar gum hydrogel (HG). The BGs were formulated at OG:HG ratios of 10:90 up to 50:50. The effect of the OG:HG ratio on appearance, microstructure, extrusion, rheological and thermal characteristics was investigated to assess printability and shape fidelity. All formulations showed no signs of phase separation during storage, while changes in color were observed with increasing OG content, suggesting modifications in phase distribution and light-scattering behavior. Increasing the OG content induced a transition from OG-in-HG systems to a bicontinuous structure at a 50:50 ratio. All inks showed shear-thinning behavior (G′ > G″) and viscoelastic properties suitable for 3D printing. BG with intermediate OG contents displayed moderate extrusion forces (7.27–9.00 N) and improved structural recovery (up to ≈60%), consistent with desirable printability and appropriate yield/flow points to ensure shape fidelity after deposition. Thermal analysis further confirmed the coexistence of OG and HG phases, ensuring structural integrity at printing temperature. These findings demonstrate the potential of BG as tunable, fat-reduced inks for 3D food structuring. Full article
(This article belongs to the Special Issue Food Hydrocolloids and Hydrogels: Rheology and Texture Analysis)
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26 pages, 2141 KB  
Article
Mitochondria-Targeted Hydrogen Sulphide Delivery via an Adhesive Hydrogel Modulates Inflammation and Oxidative Stress in Diabetic Wounds
by Mandeep Kaur Marwah, Hala Shokr, Yukta Sameer Hindalekar, Mohamad Anas Al Tahan, Karan Rana, Lissette Sanchez-Aranguren, Maymunah Sarr, Jacob Baxandall, Katy Mcgonigal, Bahareh Hassanzadeh, Shakil Ahmad, Sami A. Al-Ani, Jeevan Singh Lall, Harmony C. K. Cheema, Kavun Dhesi, Keqing Wang, Irundika H. K. Dias, Srikanth Bellary and Anisa Mahomed
Gels 2026, 12(3), 251; https://doi.org/10.3390/gels12030251 - 17 Mar 2026
Viewed by 138
Abstract
Chronic diabetic wounds are challenging to treat due to persistent inflammation, oxidative stress, impaired angiogenesis, and dysregulated matrix remodelling. Hydrogen sulphide (H2S) has emerged as a therapeutic mediator with antioxidant, anti-inflammatory, and pro-angiogenic properties; however, its clinical translation is limited by [...] Read more.
Chronic diabetic wounds are challenging to treat due to persistent inflammation, oxidative stress, impaired angiogenesis, and dysregulated matrix remodelling. Hydrogen sulphide (H2S) has emerged as a therapeutic mediator with antioxidant, anti-inflammatory, and pro-angiogenic properties; however, its clinical translation is limited by volatility and a short biological half-life. Controlled delivery systems, such as hydrogels, are therefore required to harness its potential. This study aimed to develop and evaluate a sodium 2-acrylamido-2-methylpropane sulfonate (Na-AMPS)-based adhesive hydrogel incorporating AP39, a mitochondria-targeted H2S donor, for sustained localised delivery and promotion of wound healing. Hydrogel formulations were characterised for rheological behaviour, adhesion, swelling, and AP39 release. Cytocompatibility was assessed in human umbilical vein endothelial cells (HUVECs); human dermal fibroblasts, adult (HDFa); and keratinocytes. Anti-inflammatory, antioxidant, and matrix-modulatory effects were evaluated via interleukin-6 and 8 (IL-6/IL-8) secretion, reactive oxygen species (ROS) levels, mitochondrial membrane potential, matrix metalloproteinase-9 (MMP-9), and transforming growth factor-beta (TGF-β). Functional wound healing activity was assessed using tube formation and scratch assays in endothelial cells. AP39-loaded hydrogels exhibited predominantly elastic, shear-thinning behaviour, strong adhesion, rapid hydration, and sustained release of AP39 (11.63 ± 1.20% over 24 h). Across all cell types, 500 nM concentrations of AP39 were well tolerated. In diabetic-like stress conditions, AP39 significantly decreased ROS in HUVECs (50122 ± 5999 to 33,087 ± 1865 AU; p < 0.0001) and HDFa cells (41,367 ± 4225 to 29,813 ± 2406 AU; p < 0.0001). AP39 improved mitochondrial membrane potential in both cell types (p < 0.01–0.001) and decreased pro-inflammatory cytokines. IL-6 decreased in HUVECs (96.05 ± 4.22 pg/mL to 60.99 ± 4.21 pg/mL; p < 0.0001) and HDFa cells (77.54 ± 8.94 pg/mL to 52.25 ± 6.78 pg/mL; p < 0.001), whilst in HDFa cells, MMP-9 was reduced (419.4 ± 25.51 pg/mL to 174 ± 15.1 pg/mL; p < 0.0001). Finally, wound closure was enhanced in HUVECs. The AP39-loaded Na-AMPS hydrogel represents a multifunctional wound dressing capable of controlled H2S delivery, mechanical stability, and biological activity to support tissue repair in diabetic wound environments. These results highlight this gel’s therapeutic potential for diabetic wound treatment. Full article
(This article belongs to the Section Gel Applications)
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23 pages, 614 KB  
Review
Bioactive Hydrogels and Scaffolds for Oral Mucosal Regeneration After Oral Squamous Cell Carcinoma Therapy: A Comprehensive Review
by Alina Ormenisan, Andreea Bors, Liana Beresescu, Despina Luciana Bereczki-Temistocle and Gabriela Felicia Beresescu
Medicina 2026, 62(3), 558; https://doi.org/10.3390/medicina62030558 - 17 Mar 2026
Viewed by 167
Abstract
Oral squamous cell carcinoma (OSCC) therapy frequently produces acute and chronic injury to the oral mucosa, including surgical lining defects and radiochemotherapy-associated oral mucositis (OM). Beyond pain and ulceration, these injuries compromise nutrition, speech, oral hygiene, and feasibility of dental/implant rehabilitation, and may [...] Read more.
Oral squamous cell carcinoma (OSCC) therapy frequently produces acute and chronic injury to the oral mucosa, including surgical lining defects and radiochemotherapy-associated oral mucositis (OM). Beyond pain and ulceration, these injuries compromise nutrition, speech, oral hygiene, and feasibility of dental/implant rehabilitation, and may disrupt oncologic treatment delivery. The oral cavity imposes stringent constraints on regenerative biomaterials—continuous salivary flow, high microbial load, and repeated mechanical shear—such that clinical success depends on reliable mucoadhesion/wet adhesion, barrier function, mechanical compliance, and safe, spatially confined bioactivity. This PRISMA-informed evidence-mapped structured narrative review provides an evidence map and structured qualitative synthesis of hydrogel and scaffold platforms relevant to post-OSCC care, spanning clinically used mucoadhesive barrier formulations through emerging wet-adhesive multifunctional patches, acellular matrices, and tissue-engineered oral mucosa (TEOM) constructs. Clinically, the strongest evidence base remains barrier-forming gels and liquids that reduce OM pain and improve oral function during active therapy, establishing performance benchmarks for intraoral retention and patient-reported benefit. Preclinical studies are rapidly expanding toward multifunctional designs that integrate antimicrobial, anti-inflammatory, pro-epithelialization, and pro-angiogenic cues. However, a pervasive limitation is the inconsistent use of OSCC-relevant models (e.g., irradiated/xerostomic tissue beds), standardized functional endpoints (e.g., oral intake, durability under mastication, and neurosensory outcomes), and explicit oncologic safety evaluation, which severely compromises translational validity. For reconstructive applications, dermal matrices and early TEOM reports suggest feasibility for selected defects, but controlled comparative trials and scalable manufacturing pathways remain limited. Translational priorities include oncologic-by-design bioactivity (time-limited, locally confined cues), clinically anchored outcome reporting, and quality-by-design manufacturing aligned with device/combination/advanced-therapy regulatory requirements. Full article
(This article belongs to the Special Issue Regenerative Dentistry: A New Paradigm in Oral Health Care)
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23 pages, 11154 KB  
Article
Oxidized Dextran/Carboxymethyl Chitosan Dynamic Schiff-Base Hydrogel for Sustained Hydrogen Sulfide Delivery and Burn Wound Microenvironment Remodeling
by Zhishan Liu, Ying Zhu, Zhuoya Ma, Xuyang Ning, Ziqiang Zhou, Jinchang Liu, Youfu Xie, Gang Li and Ping Hu
Pharmaceutics 2026, 18(3), 370; https://doi.org/10.3390/pharmaceutics18030370 - 17 Mar 2026
Viewed by 129
Abstract
Background: Polysaccharide-based dynamic hydrogels are promising for wound management due to their biocompatibility, injectability, and tunable biofunctionality. The integration of therapeutic gasotransmitter donors offers a strategy to modulate the wound microenvironment. Objectives: This study aimed to develop an injectable, self-healing carbohydrate [...] Read more.
Background: Polysaccharide-based dynamic hydrogels are promising for wound management due to their biocompatibility, injectability, and tunable biofunctionality. The integration of therapeutic gasotransmitter donors offers a strategy to modulate the wound microenvironment. Objectives: This study aimed to develop an injectable, self-healing carbohydrate hydrogel capable of sustained hydrogen sulfide (H2S) release for burn wound therapy, and to evaluate its physicochemical properties, in vivo efficacy, and mechanism of action. Methods: A dynamic hydrogel (ACMOD) was fabricated via Schiff-base crosslinking between oxidized dextran (OD) and carboxymethyl chitosan (CMCS), incorporating the H2S donor 5-(4-hydroxyphenyl)-3H-1,2-dithiole-3-thione (ADT-OH). Rheological and recovery tests characterized its mechanical and self-healing properties. Efficacy and mechanisms were assessed in a rat full-thickness burn model, analyzing wound closure, histology, oxidative stress, macrophage polarization, angiogenesis, and collagen deposition. Results: ACMOD exhibited shear-thinning, rapid self-healing, and strong tissue adherence. Sustained H2S release from ACMOD significantly accelerated wound closure and improved tissue regeneration compared to controls. Mechanistically, H2S attenuated oxidative stress, promoted a pro-regenerative M2 macrophage phenotype, enhanced angiogenesis via VEGF upregulation, and fostered organized collagen deposition and extracellular matrix remodeling. Conclusions: This work demonstrates a versatile, carbohydrate-based dynamic hydrogel platform that synergizes polymer network dynamics with bioactive H2S delivery to effectively promote burn wound healing. The findings underscore the potential of polysaccharide hydrogels with integrated gasotransmitter release for regenerative therapy and biomaterials applications. Full article
(This article belongs to the Section Drug Delivery and Controlled Release)
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23 pages, 3404 KB  
Review
Alginate-Based Biomaterials: From Fundamental “Egg-Box” Chemistry to Diverse Biomedical and Metabolic Management of Obesity and Diabetes
by Adnan Alsaei, Ahmad Zarwi, Ayah Binrajab, Fatema Rahimi, Renad AlAnsari, Manyam Praveen Kumar, Alexandra E. Butler, Stephen L. Atkin and G. Roshan Deen
Gels 2026, 12(3), 250; https://doi.org/10.3390/gels12030250 - 17 Mar 2026
Viewed by 227
Abstract
Alginate, a naturally occurring polysaccharide derived from brown algae, has emerged as a versatile cornerstone in the field of biomedical materials. Its widespread adoption is driven by its exceptional biocompatibility and the unique cation-dependent gelation defined by the “egg-box” model. This review examines [...] Read more.
Alginate, a naturally occurring polysaccharide derived from brown algae, has emerged as a versatile cornerstone in the field of biomedical materials. Its widespread adoption is driven by its exceptional biocompatibility and the unique cation-dependent gelation defined by the “egg-box” model. This review examines the fundamental chemistry of alginate, detailing how its crosslinking mechanisms dictate the physicochemical properties essential for clinical performance. The discussion bridges the gap between polymer structure and diverse biomedical applications, including drug delivery, tissue engineering, and the clinical management of gastrointestinal reflux and wound care. Furthermore, the article evaluates the role of alginate-based systems in the biomedical and metabolic management of obesity and diabetes. By analyzing how alginate influences satiety, glycemic index modulation, and lipid absorption through biophysical mechanisms, this review highlights the transition from fundamental chemical architecture to practical clinical utility. By integrating structural chemistry with physiological impact, this work underscores the evolving potential of alginate-based materials as supportive and functional strategies in modern clinical care. Full article
(This article belongs to the Section Gel Processing and Engineering)
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12 pages, 1282 KB  
Proceeding Paper
Study of the Removal of Organic Pollutants from Aqueous Solutions Using Organic Hydrogels and Biochars
by Paraskevi Souliou, Eleni Grilla, Alexandra A. Ioannidi and Vlasoula Bekiari
Environ. Earth Sci. Proc. 2026, 40(1), 9; https://doi.org/10.3390/eesp2026040009 - 16 Mar 2026
Viewed by 86
Abstract
Aquifers are increasingly threatened by the uncontrolled release of non-biodegradable chemicals derived from anthropogenic activities. The development of new remediation strategies has therefore focused on the use of sustainable adsorbent materials, including synthetic organic hydrogels and biochars produced from agricultural residues. In this [...] Read more.
Aquifers are increasingly threatened by the uncontrolled release of non-biodegradable chemicals derived from anthropogenic activities. The development of new remediation strategies has therefore focused on the use of sustainable adsorbent materials, including synthetic organic hydrogels and biochars produced from agricultural residues. In this study, the removal of two organic pollutants, the herbicide Metribuzin (MEB) and Propyl Paraben (PrP), from aqueous environments was investigated using negatively charged hydrogels and biochars derived from lime peel, respectively. Propyl Paraben (PrP) and Metribuzin (MEB) are among the pollutants frequently found in aquatic environments, and the effective and sustainable removal approaches remain under investigation. The hydrogels studied (P(DMAM co-ANax)) were based on sodium methacrylate (ANa) copolymerized with N,N-dimethylacrylamide (DMAM). The adsorption performance of the materials was evaluated through UV-Visible absorption spectrophotometry and High-Performance Liquid Chromatography (HPLC). The results of this study showed that the hydrogel achieved a very high removal efficiency for MEB, which was over 80% for the concentration range studied (max Qe = 0.386 mg/g). Similar behavior was also recorded for the biochar from lime peel, which achieved almost complete removal of PrP (~100%) at the lowest concentrations of the contaminant (5 mg/L) and maintained high removal rates (78%) at 10 mg/L (max Qe = 0.187 mg/g). These results demonstrate the potential of both types of materials to efficiently remove the studied contaminants from water, indicating their suitability for environmental remediation applications. This work contributes to the development of cost-effective and eco-friendly adsorbents for the treatment of water pollution caused by emerging organic compounds. Full article
(This article belongs to the Proceedings of The 9th International Electronic Conference on Water Sciences)
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50 pages, 1763 KB  
Review
Next-Generation Hydrogels Integrating Natural Antioxidants and Microbiome Modulators for Improved Cancer Management
by Camelia Munteanu, Eftimia Prifti, Larisa Achim, Ciprian Nicolae Silaghi and Sorin Marian Mârza
Gels 2026, 12(3), 249; https://doi.org/10.3390/gels12030249 - 16 Mar 2026
Viewed by 153
Abstract
Cancer remains a leading cause of death worldwide, and current treatments are often limited by toxicity and resistance. Emerging research highlights the crucial roles played by gut microbiome dysbiosis and oxidative stress in cancer development and treatment response. Through their antioxidant, anti-inflammatory, and [...] Read more.
Cancer remains a leading cause of death worldwide, and current treatments are often limited by toxicity and resistance. Emerging research highlights the crucial roles played by gut microbiome dysbiosis and oxidative stress in cancer development and treatment response. Through their antioxidant, anti-inflammatory, and immunomodulatory properties, natural antioxidants such as resveratrol, along with microbiome modulators like probiotics, prebiotics, and synbiotics, offer promising therapeutic benefits. However, issues such as low bioavailability, instability, and challenges related to targeted delivery hinder the clinical translation of these bioactive compounds. Next-generation hydrogels have emerged as adaptable platforms capable of delivering and protecting these agents in a site-specific and controlled manner. This review summarizes the design and synthesis of multifunctional hydrogels incorporating natural antioxidants and microbiome modulators for cancer therapy. Full article
(This article belongs to the Special Issue Recent Advances in Gel-Based Materials for Cancer Therapy)
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13 pages, 3727 KB  
Article
Transcutaneous Electrical Nerve Stimulation Based on a Microneedle/Hydrogel Composite System
by Xiangyu Li, Donghao Li, Yuqi Wang, Peng Tian and Yunfeng Wang
Appl. Sci. 2026, 16(6), 2841; https://doi.org/10.3390/app16062841 - 16 Mar 2026
Viewed by 108
Abstract
Transcutaneous electrical nerve stimulation (TENS) is constrained by high skin impedance and unstable electrode contact. This study proposes a novel composite electrode system comprising a polyvinyl alcohol/silver (PVA/Ag) microneedle array and a highly conductive polyacrylamide/lithium chloride (PAAm/LiCl) hydrogel. The PVA/Ag microneedles (~365 µm [...] Read more.
Transcutaneous electrical nerve stimulation (TENS) is constrained by high skin impedance and unstable electrode contact. This study proposes a novel composite electrode system comprising a polyvinyl alcohol/silver (PVA/Ag) microneedle array and a highly conductive polyacrylamide/lithium chloride (PAAm/LiCl) hydrogel. The PVA/Ag microneedles (~365 µm in height, ~48 µm tip diameter) possess sufficient mechanical strength to penetrate the stratum corneum, establishing a low-resistance pathway. The complementary PAAm/LiCl hydrogel exhibits high conductivity (10.28 S/m) and mechanical flexibility, further optimizing the interface contact. The experimental results demonstrate that this composite system achieves low electrochemical impedance and induces stable, clear electromyographic responses in vivo. It effectively addresses the common issues of electrode detachment and signal attenuation associated with conventional electrodes, offering a promising hardware solution for efficient and comfortable wearable rehabilitation devices. Full article
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21 pages, 975 KB  
Review
Structure–Mechanical Relationships in Alginate–Chitosan Polymer Composites
by Hatice Sıçramaz
Polymers 2026, 18(6), 713; https://doi.org/10.3390/polym18060713 - 15 Mar 2026
Viewed by 145
Abstract
Alginate–chitosan composites are widely used bio-based materials due to their biocompatibility, biodegradability, and relatively simple processing methods. By combining the complementary properties of alginate and chitosan, these systems offer adjustable mechanical characteristics suitable for applications such as tissue engineering, wound healing, drug delivery, [...] Read more.
Alginate–chitosan composites are widely used bio-based materials due to their biocompatibility, biodegradability, and relatively simple processing methods. By combining the complementary properties of alginate and chitosan, these systems offer adjustable mechanical characteristics suitable for applications such as tissue engineering, wound healing, drug delivery, and sustainable packaging. However, although many studies report improved mechanical properties, the link between structural design and mechanical behavior is often discussed within specific applications rather than examined in a broader context. This review focuses on how polymer ratio, charge balance, crosslinking strategy, reinforcement approach, and processing conditions influence the mechanical properties of alginate–chitosan composites. Instead of considering these factors separately, the available studies are discussed in terms of how the internal structure of the composite affects stiffness, strength, deformability, and stability. This review brings together findings from various fields to highlight shared structure–mechanical relationships and to provide guidance for designing alginate–chitosan composites with specific mechanical properties. Full article
(This article belongs to the Special Issue Advanced Polymer Composites: Structure and Mechanical Properties)
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58 pages, 10581 KB  
Review
Hydrogels—Advanced Polymer Platforms for Drug Delivery
by Rodica Ene (Vatcu), Andreea-Teodora Iacob, Iuliu Fulga, Maria Luisa Di Gioia, Ionut Dragostin, Ana Fulga, Sangram Keshari Samal and Oana-Maria Dragostin
Polymers 2026, 18(6), 709; https://doi.org/10.3390/polym18060709 - 14 Mar 2026
Viewed by 456
Abstract
Optimizing drug administration remains a central challenge in the development of modern therapies, especially in the context of conditions that require spatiotemporal control of active substance release. In this context, hydrogels have been intensively investigated as polymeric platforms for drug delivery, through their [...] Read more.
Optimizing drug administration remains a central challenge in the development of modern therapies, especially in the context of conditions that require spatiotemporal control of active substance release. In this context, hydrogels have been intensively investigated as polymeric platforms for drug delivery, through their three-dimensional hydrophilic structure, tunable properties, and compatibility with biological environments. This analysis presents an integrated approach to hydrogels used in drug administration, addressing the physicochemical fundamentals, the constitutive polymeric materials, and the mechanisms of response to relevant physiological stimuli. Recent experimental studies have been discussed, which highlight the use of hydrogels based on natural, synthetic, and hybrid polymers for controlled and targeted release, in correlation with various administration routes, including oral, injectable, transmucosal, and topical ones. Advanced functionalization strategies that allow adaptive responses to pH, temperature, glucose, enzymes, and reactive oxygen species are also analyzed. Furthermore, emerging directions integrating hydrogels with biosensors, microdevices, and wireless communication systems for real-time monitoring and on-demand release are highlighted. Overall, the analysis emphasizes the role of smart hydrogels as multifunctional platforms for complex therapeutic strategies while also underlining the current challenges associated with clinical translation and long-term performance. Full article
(This article belongs to the Special Issue Advanced Polymeric Biomaterials for Drug Delivery Applications)
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19 pages, 7257 KB  
Article
Gelatin/Lignin Hydrogel Loaded with Mesenchymal Stem Cell-Derived Exosomes Enriched in Microrna-185 Inhibits Progression of Oral Cancer
by Meitong Liu, Kai Wang, Can Zeng, Yijiang Jia, Jiaqi Wang, Ayijiang Taledaohan, Yuji Wang and Xiaobing Guan
Pharmaceutics 2026, 18(3), 363; https://doi.org/10.3390/pharmaceutics18030363 - 14 Mar 2026
Viewed by 207
Abstract
Purpose: Due to the lack of effective local therapeutic strategies for oral squamous cell carcinoma (OSCC), this study aimed to develop a novel gelatin/lignin hydrogel loaded with mesenchymal stem cell (MSC)-derived exosomes enriched in microRNA-185 (miR-185 EV) for intraoral delivery, followed by systematic [...] Read more.
Purpose: Due to the lack of effective local therapeutic strategies for oral squamous cell carcinoma (OSCC), this study aimed to develop a novel gelatin/lignin hydrogel loaded with mesenchymal stem cell (MSC)-derived exosomes enriched in microRNA-185 (miR-185 EV) for intraoral delivery, followed by systematic evaluation of its therapeutic efficacy and underlying molecular mechanisms. Materials and Methods: The gelatin/lignin hydrogel was prepared and subsequently loaded with miR-185 EV. The physicochemical properties of the hydrogel, including microstructure, swelling behavior, chemical composition, and rheological characteristics, were systematically evaluated. Next, the stability, viscosity, biocompatibility, and exosome release kinetics of the hydrogel were further assessed. A 4-nitroquinoline-1-oxide (4NQO)-induced mouse tongue carcinogenesis model was established to assess the in vivo antitumor activity of the hydrogel via intraoral administration. Moreover, a proteomic analysis was conducted to investigate the molecular mechanisms of miR-185 EV on OSCC. Results: The miR-185 EV-loaded gelatin/lignin hydrogel exhibited favorable physicochemical properties, stability, and biocompatibility while prolonging the tissue retention time of miR-185 EV. In vivo antitumor efficacy experiments showed that the miR-185 EV-loaded hydrogel significantly inhibited tumor occurrence and alleviated epithelial dysplasia. Immunohistochemical analyses revealed significant suppression of tumor proliferation and epithelial–mesenchymal transition (EMT) of the hydrogel. Proteomic analysis indicated that miR-185 EV suppressed OSCC progression by downregulating interleukin-1β (IL-1β), consequently inhibiting the NF-κB signaling pathway. Conclusion: The findings demonstrate the successful development of the miR-185 EV-loaded gelatin/lignin hydrogel that represents an effective nanomedicine platform for intraoral drug delivery, providing a promising strategy for the clinical treatment of OSCC. Full article
(This article belongs to the Section Drug Delivery and Controlled Release)
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17 pages, 1981 KB  
Article
Tailoring the Design of Dendritic Thermogels Through Carbosilane and Polyglycerol Crosslinkers
by Judith Recio-Ruiz, Boonya Thongrom, F. Javier de la Mata, Rainer Haag and Sandra García-Gallego
Pharmaceutics 2026, 18(3), 362; https://doi.org/10.3390/pharmaceutics18030362 - 13 Mar 2026
Viewed by 205
Abstract
Background/Objectives: The development of stimuli-responsive hydrogels for biomedical uses is an intense field of research. The use of dendritic crosslinkers can enhance the control over the structure and properties of the networks. This work presents a comparative study on the design and evaluation [...] Read more.
Background/Objectives: The development of stimuli-responsive hydrogels for biomedical uses is an intense field of research. The use of dendritic crosslinkers can enhance the control over the structure and properties of the networks. This work presents a comparative study on the design and evaluation of Pluronic L35 thermogels, incorporating either hydrophobic carbosilane dendrimers (CBS, generations 1 to 3) or hydrophilic dendritic polyglycerols (dPG, 10 k) as crosslinkers. Methods: The thermogels were synthesized via UV-initiated thiol–ene click chemistry. Additionally, they were characterized through swelling studies, mechanical properties, degradation kinetics as well as loading and release studies of the antitumor drug doxorubicin as poorly soluble model cargo. Results: The incorporation of dendritic crosslinkers allowed higher control over the crosslinking process, while the amphiphilic polymer imparted temperature-responsive properties to the resulting networks. Remarkable differences were observed in swelling behavior, mechanical properties and degradation kinetics, depending on the nature of the dendritic crosslinker. Additionally, regarding doxorubicin loading and release in water, CBS hydrogels produced a sustained release over one week, led by network swelling, while dPG hydrogels exhibited a burst release in 4–24 h but were limited by the stronger interaction of DOX with the dPG scaffold. Conclusions: The study provided useful insight for the tailoring of dendritic thermogels for specific biomedical uses such as controlled drug delivery. Full article
(This article belongs to the Special Issue Dendrimers in Nanomedicine: Recent Advances)
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12 pages, 1574 KB  
Article
High-Performance Gel Design for Flexible Pressure-Sensing Films in Taekwondo Applications
by Zhiyong Zhang, Weimin Pan, Qianle Zhang, Yi Men, Niankun Zhang and Tao Liu
Gels 2026, 12(3), 244; https://doi.org/10.3390/gels12030244 - 13 Mar 2026
Viewed by 115
Abstract
Exploring effective training methods to reliably trigger scoring in electronic protective gear is a significant challenge faced by coaches and athletes, and it constitutes a critical research direction that urgently demands scientific exploration. To improve the scientific precision of daily Taekwondo training and [...] Read more.
Exploring effective training methods to reliably trigger scoring in electronic protective gear is a significant challenge faced by coaches and athletes, and it constitutes a critical research direction that urgently demands scientific exploration. To improve the scientific precision of daily Taekwondo training and enhance competitive performance more efficiently and to improve the effectiveness of daily Taekwondo training and enhance competitive performance, a hydrogel-based flexible pressure-sensing film was developed. This film would enable traditional Taekwondo protective gear with electronic sensing capabilities via a simple adhesion method. By attaching a low-cost, high-precision, and appropriately flexible gel-based pressure-sensing film to conventional protective gear through a straightforward adhesion approach, it can attain sensing performance comparable to that of specialized competition-grade electronic protective gear. This innovation will provide technological support for advancing the scientific rigor of Taekwondo training in China. This study focuses on the design and development of high-strength, high-toughness ionic hydrogels, offering technical backing for the creation of flexible pressure-sensing films tailored for Taekwondo applications. Full article
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