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Search Results (739)

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Keywords = degradable hydrogels

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32 pages, 5531 KiB  
Review
Polyethylenimine Carriers for Drug and Gene Delivery
by Ahmed Ismail and Shih-Feng Chou
Polymers 2025, 17(15), 2150; https://doi.org/10.3390/polym17152150 - 6 Aug 2025
Abstract
Polyethylenimine (PEI) is a cationic polymer with a high density of amine groups suitable for strong electrostatic interactions with biological molecules to preserve their bioactivities during encapsulation and after delivery for biomedical applications. This review provides a comprehensive overview of PEI as a [...] Read more.
Polyethylenimine (PEI) is a cationic polymer with a high density of amine groups suitable for strong electrostatic interactions with biological molecules to preserve their bioactivities during encapsulation and after delivery for biomedical applications. This review provides a comprehensive overview of PEI as a drug and gene carrier, describing its polymerization methods in both linear and branched forms while highlighting the processing methods to manufacture PEIs into drug carriers, such as nanoparticles, coatings, nanofibers, hydrogels, and films. These various PEI carriers enable applications in non-viral gene and small molecule drug deliveries. The structure–property relationships of PEI carriers are discussed with emphasis on how molecular weights, branching degrees, and surface modifications of PEI carriers impact biocompatibility, transfection efficiency, and cellular interactions. While PEI offers remarkable potential for drug and gene delivery, its clinical translation remains limited by challenges, including cytotoxicity, non-degradability, and serum instability. Our aim is to provide an understanding of PEI and the structure–property relationships of its carrier forms to inform future research directions that may enable safe and effective clinical use of PEI carriers for drug and gene delivery. Full article
(This article belongs to the Special Issue Biocompatible and Biodegradable Polymer Materials)
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14 pages, 2315 KiB  
Article
A Portable and Thermally Degradable Hydrogel Sensor Based on Eu-Doped Carbon Dots for Visual and Ultrasensitive Detection of Ferric Ion
by Hongyuan Zhang, Qian Zhang, Juan Tang, Huanxin Yang, Xiaona Ji, Jieqiong Wang and Ce Han
Molecules 2025, 30(15), 3280; https://doi.org/10.3390/molecules30153280 - 5 Aug 2025
Abstract
Degradable fluorescent sensors present a promising portable approach for heavy metal ion detection, aiming to prevent secondary environmental pollution. Additionally, the excessive intake of ferric ions (Fe3+), an essential trace element for human health, poses critical health risks that urgently require [...] Read more.
Degradable fluorescent sensors present a promising portable approach for heavy metal ion detection, aiming to prevent secondary environmental pollution. Additionally, the excessive intake of ferric ions (Fe3+), an essential trace element for human health, poses critical health risks that urgently require effective monitoring. In this study, we developed a thermally degradable fluorescent hydrogel sensor (Eu-CDs@DPPG) based on europium-doped carbon dots (Eu-CDs). The Eu-CDs, synthesized via a hydrothermal method, exhibited selective fluorescence quenching by Fe3+ through the inner filter effect (IFE). Embedding Eu-CDs into the hydrogel significantly enhanced their stability and dispersibility in aqueous environments, effectively resolving issues related to aggregation and matrix interference in traditional sensing methods. The developed sensor demonstrated a broad linear detection range (0–2.5 µM), an extremely low detection limit (1.25 nM), and rapid response (<40 s). Furthermore, a smartphone-assisted LAB color analysis allowed portable, visual quantification of Fe3+ with a practical LOD of 6.588 nM. Importantly, the hydrogel was thermally degradable at 80 °C, thus minimizing environmental impact. The sensor’s practical applicability was validated by accurately detecting Fe3+ in spinach and human urine samples, achieving recoveries of 98.7–108.0% with low relative standard deviations. This work provides an efficient, portable, and sustainable sensing platform that overcomes the limitations inherent in conventional analytical methods. Full article
(This article belongs to the Section Photochemistry)
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19 pages, 6111 KiB  
Article
Impact of Water Conductivity on the Structure and Swelling Dynamics of E-Beam Cross-Linked Hydrogels
by Elena Mănăilă, Ion Călina, Anca Scărișoreanu, Maria Demeter, Gabriela Crăciun and Marius Dumitru
Gels 2025, 11(8), 611; https://doi.org/10.3390/gels11080611 - 4 Aug 2025
Viewed by 154
Abstract
Prolonged drought and soil degradation severely affect soil fertility and limit crop productivity. Superabsorbent hydrogels offer an effective solution for improving water retention in soil and supporting plant growth. In this work, we examined the performance of superabsorbent hydrogels based on sodium alginate, [...] Read more.
Prolonged drought and soil degradation severely affect soil fertility and limit crop productivity. Superabsorbent hydrogels offer an effective solution for improving water retention in soil and supporting plant growth. In this work, we examined the performance of superabsorbent hydrogels based on sodium alginate, acrylic acid (AA), and poly (ethylene oxide) (PEO) cross-linked with 12.5 kGy using e-beam irradiation. The hydrogels were assessed in various aqueous environments by examining network characteristics, swelling capacity, and swelling kinetics to evaluate the impact of water’s electrical conductivity (which ranges from 0.05 to 321 μS/cm). Morphological and chemical structure changes were evaluated using SEM and FTIR techniques. The results demonstrated that water conductivity significantly affected the physicochemical properties of the hydrogels. Swelling behavior showed notable sensitivity to electrical conductivity variations, with swelling degrees reaching 28,400% at 5 μS/cm and 14,000% at 321 μS/cm, following first-order and second-order kinetics. FTIR analysis confirmed that structural modifications correlated with water conductivity, particularly affecting the O–H, C–H, and COOH groups sensitive to the ionic environment. SEM characterization revealed a porous morphology with an interconnected microporous network that facilitates efficient water diffusion. These hydrogels show exceptional swelling capacity and are promising candidates for sustainable agriculture applications. Full article
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14 pages, 2448 KiB  
Article
Study on the Semi-Interpenetrating Polymer Network Self-Degradable Gel Plugging Agent for Deep Coalbed Methane
by Bo Wang, Zhanqi He, Jin Lin, Kang Ren, Zhengyang Zhao, Kaihe Lv, Yiting Liu and Jiafeng Jin
Processes 2025, 13(8), 2453; https://doi.org/10.3390/pr13082453 - 3 Aug 2025
Viewed by 160
Abstract
Deep coalbed methane (CBM) reservoirs are characterized by high hydrocarbon content and are considered an important strategic resource. Due to their inherently low permeability and porosity, horizontal well drilling is commonly employed to enhance production, with the length of the horizontal section playing [...] Read more.
Deep coalbed methane (CBM) reservoirs are characterized by high hydrocarbon content and are considered an important strategic resource. Due to their inherently low permeability and porosity, horizontal well drilling is commonly employed to enhance production, with the length of the horizontal section playing a critical role in determining CBM output. However, during extended horizontal drilling, wellbore instability frequently occurs as a result of drilling fluid invasion into the coal formation, posing significant safety challenges. This instability is primarily caused by the physical intrusion of drilling fluids and their interactions with the coal seam, which alter the mechanical integrity of the formation. To address these challenges, interpenetrating and semi-interpenetrating network (IPN/s-IPN) hydrogels have gained attention due to their superior physicochemical properties. This material offers enhanced sealing and support performance across fracture widths ranging from micrometers to millimeters, making it especially suited for plugging applications in deep CBM reservoirs. A self-degradable interpenetrating double-network hydrogel particle plugging agent (SSG) was developed in this study, using polyacrylamide (PAM) as the primary network and an ionic polymer as the secondary network. The SSG demonstrated excellent thermal stability, remaining intact for at least 40 h in simulated formation water at 120 °C with a degradation rate as high as 90.8%, thereby minimizing potential damage to the reservoir. After thermal aging at 120 °C, the SSG maintained strong plugging performance and favorable viscoelastic properties. A drilling fluid containing 2% SSG achieved an invasion depth of only 2.85 cm in an 80–100 mesh sand bed. The linear viscoelastic region (LVR) ranged from 0.1% to 0.98%, and the elastic modulus reached 2100 Pa, indicating robust mechanical support and deformation resistance. Full article
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22 pages, 1268 KiB  
Review
Natural Polymer-Based Hydrogel Platforms for Organoid and Microphysiological Systems: Mechanistic Insights and Translational Perspectives
by Yeonoh Cho, Jungmok You and Jong Hun Lee
Polymers 2025, 17(15), 2109; https://doi.org/10.3390/polym17152109 - 31 Jul 2025
Viewed by 354
Abstract
Organoids and microphysiological systems (MPSs) have emerged as physiologically relevant platforms that recapitulate key structural and functional features of human organs, tissues, and microenvironments. As one of the essential components that define the success of these systems, hydrogels play the central role of [...] Read more.
Organoids and microphysiological systems (MPSs) have emerged as physiologically relevant platforms that recapitulate key structural and functional features of human organs, tissues, and microenvironments. As one of the essential components that define the success of these systems, hydrogels play the central role of providing a three-dimensional, biomimetic scaffold that supports cell viability, spatial organization, and dynamic signaling. Natural polymer-based hydrogels, derived from materials such as collagen, gelatin, hyaluronic acid, and alginate, offer favorable properties including biocompatibility, degradability, and an extracellular matrix-like architecture. This review presents recent advances in the design and application of such hydrogels, focusing on crosslinking strategies (physical, chemical, and hybrid), the viscoelastic characteristics, and stimuli-responsive behaviors. The influence of these materials on cellular processes, such as stemness maintenance, differentiation, and morphogenesis, is critically examined. Furthermore, the applications of organoid culture and dynamic MPS platforms are discussed, highlighting their roles in morphogen delivery, barrier formation, and vascularization. Current challenges and future perspectives toward achieving standardized, scalable, and translational hydrogel systems are also addressed. Full article
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11 pages, 2406 KiB  
Article
Surfactant-Free Electrosprayed Alginate Beads for Oral Delivery of Hydrophobic Compounds
by Hye-Seon Jeong, Hyo-Jin Kim, Sung-Min Kang and Chang-Hyung Choi
Polymers 2025, 17(15), 2098; https://doi.org/10.3390/polym17152098 - 30 Jul 2025
Viewed by 198
Abstract
Oral delivery of hydrophobic compounds remains challenging due to their poor aqueous solubility and the potential toxicity associated with conventional surfactant-based emulsions. To address these issues, we present a surfactant-free encapsulation strategy using electrosprayed alginate hydrogel beads for the stable and controlled delivery [...] Read more.
Oral delivery of hydrophobic compounds remains challenging due to their poor aqueous solubility and the potential toxicity associated with conventional surfactant-based emulsions. To address these issues, we present a surfactant-free encapsulation strategy using electrosprayed alginate hydrogel beads for the stable and controlled delivery of hydrophobic oils. Hydrophobic compounds were dispersed in high-viscosity alginate solutions without surfactants via ultrasonication, forming kinetically stable oil-in-water dispersions. These mixtures were electrosprayed into calcium chloride baths, yielding monodisperse hydrogel beads. Higher alginate concentrations improved droplet sphericity and suppressed phase separation by enhancing matrix viscosity. The resulting beads exhibited stimuli-responsive degradation and controlled release behavior in response to physiological ionic strength. Dense alginate networks delayed ion exchange and prolonged structural integrity, while elevated external ionic conditions triggered rapid disintegration and immediate payload release. This simple and scalable system offers a biocompatible platform for the oral delivery of lipophilic active compounds without the need for surfactants or complex fabrication steps. Full article
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14 pages, 1259 KiB  
Review
Engineered Hydrogels for Musculoskeletal Regeneration: Advanced Synthesis Strategies and Therapeutic Efficacy in Preclinical Models
by Gabriela Calin, Mihnea Costescu, Marcela Nour (Cârlig), Tudor Ciuhodaru, Batîr-Marin Denisa, Letitia Doina Duceac, Cozmin Mihai, Melania Florina Munteanu, Svetlana Trifunschi, Alexandru Oancea and Daniela Liliana Damir
Polymers 2025, 17(15), 2094; https://doi.org/10.3390/polym17152094 - 30 Jul 2025
Viewed by 255
Abstract
According to the World Health Organization, musculoskeletal injuries affect more than 1.71 billion people around the world. These injuries are a major public health issue and the leading cause of disability. There has been a recent interest in hydrogels as a potential biomaterial [...] Read more.
According to the World Health Organization, musculoskeletal injuries affect more than 1.71 billion people around the world. These injuries are a major public health issue and the leading cause of disability. There has been a recent interest in hydrogels as a potential biomaterial for musculoskeletal tissue regeneration. This is due to their high water content (70–99%), ECM-like structure, injectability, and controllable degradation rates. Recent preclinical studies indicate that they can enhance regeneration by modulating the release of bioactive compounds, growth factors, and stem cells. Composite hydrogels that combine natural and synthetic polymers, like chitosan and collagen, have compressive moduli that are advantageous for tendon–bone healing. Some of these hydrogels can even hold up to 0.8 MPa of tensile strength. In osteoarthritis models, functionalized systems such as microspheres responsive to matrix metalloproteinase-13 have demonstrated disease modulation and targeted drug delivery, while intelligent in situ hydrogels have exhibited a 43% increase in neovascularization and a 50% enhancement in myotube production. Hydrogel-based therapies have been shown to restore contractile force by as much as 80%, increase myofiber density by 65%, and boost ALP activity in bone defects by 2.1 times in volumetric muscle loss (VML) models. Adding TGF-β3 or MSCs to hydrogel systems improved GAG content by about 60%, collagen II expression by 35–50%, and O’Driscoll scores by 35–50% in cartilage regeneration. Full article
(This article belongs to the Section Polymer Applications)
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15 pages, 15023 KiB  
Article
Surface-Localized Crosslinked MEW PCL–Hydrogel Scaffolds with Tunable Porosity for Enhanced Cell Adhesion and Viability
by Yixin Li, Le Kang and Kai Cao
Polymers 2025, 17(15), 2086; https://doi.org/10.3390/polym17152086 - 30 Jul 2025
Viewed by 269
Abstract
Hydrogel is widely used as a scaffolding material for tissue engineering due to its excellent cytocompatibility and potential for biofunctionalization. However, its poor mechanical property limits its further application. Fabrication of fiber-reinforced hydrogel composite scaffolds has emerged as a solution to overcome this [...] Read more.
Hydrogel is widely used as a scaffolding material for tissue engineering due to its excellent cytocompatibility and potential for biofunctionalization. However, its poor mechanical property limits its further application. Fabrication of fiber-reinforced hydrogel composite scaffolds has emerged as a solution to overcome this problem. However, existing strategies usually produce nonporous composite scaffolds, where the interfiber pores are completely filled with hydrogel. This design can hinder oxygen and nutrient exchange between seeded cells and the culture medium, thereby limiting cell invasion and colonization within the scaffold. In this study, sodium alginate (SA) hydrogel was exclusively grafted onto the surface of the constituent fibers of the melt electrowritten scaffold while preserving the porous structure. The grafted hydrogel amount and pore size were precisely controlled by adjusting the SA concentration and the crosslinking ratio (SA: CaCl2). Experimental results demonstrated that the porous composite scaffolds exhibited superior swelling capacity, degradation ratio, mechanical properties, and biocompatibility. Notably, at an SA concentration of 0.5% and a crosslinking ratio of 2:1, the porous composite scaffold achieved optimal cell adhesion and viability. This study highlights the critical importance of preserving porous structures in composite scaffolds for tissue-engineering applications. Full article
(This article belongs to the Section Polymer Networks and Gels)
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19 pages, 3224 KiB  
Article
Supramolecular Co-Assembled Fmoc-FRGDF/Hyaluronic Acid Hydrogel for Quercetin Delivery: Multifunctional Bioactive Platform
by Xian-Ni Su, Yu-Yang Wang, Muhammed Fahad Khan, Li-Na Zhu, Zhong-Liang Chen, Zhuo Wang, Bing-Bing Song, Qiao-Li Zhao, Sai-Yi Zhong and Rui Li
Foods 2025, 14(15), 2629; https://doi.org/10.3390/foods14152629 - 26 Jul 2025
Viewed by 361
Abstract
Background: During food processing and storage, traditional protein-based delivery systems encounter significant challenges in maintaining the structural and functional integrity of bioactive compounds, primarily due to their temporal instability. Methods: In this study, a nanocomposite hydrogel was prepared through the co-assembly of a [...] Read more.
Background: During food processing and storage, traditional protein-based delivery systems encounter significant challenges in maintaining the structural and functional integrity of bioactive compounds, primarily due to their temporal instability. Methods: In this study, a nanocomposite hydrogel was prepared through the co-assembly of a self-assembling peptide, 9-Fluorenylmethoxycarbonyl-phenylalanine-arginine-glycine-aspartic acid-phenylalanine (Fmoc-FRGDF), and hyaluronic acid (HA). The stability of this hydrogel as a quercetin (Que) delivery carrier was systematically investigated. Furthermore, the impact of Que co-assembly on the microstructural evolution and physicochemical properties of the hydrogel was characterized. Concurrently, the encapsulation efficiency (EE%) and controlled release kinetics of Que were quantitatively evaluated. Results: The findings indicated that HA significantly reduced the storage modulus (G′) from 256.5 Pa for Fmoc-FRGDF to 21.1 Pa with the addition of 0.1 mg/mL HA. Despite this reduction, HA effectively slowed degradation rates; specifically, residue rates of 5.5% were observed for Fmoc-FRGDF alone compared to 14.1% with 0.5 mg/mL HA present. Notably, Que enhanced G′ within the ternary complex, increasing it from 256.5 Pa in Fmoc-FRGDF to an impressive 7527.0 Pa in the Que/HA/Fmoc-FRGDF hydrogel containing 0.1 mg/mL HA. The interactions among Que, HA, and Fmoc-FRGDF involved hydrogen bonding, electrostatic forces, and hydrophobic interactions; furthermore, the co-assembly process strengthened the β-sheet structure while significantly promoting supramolecular ordering. Interestingly, the release profile of Que adhered to the Korsmeyer–Peppas pharmacokinetic equations. Conclusions: Overall, this study examines the impact of polyphenol on the rheological properties, microstructural features, secondary structure conformation, and supramolecular ordering within peptide–polysaccharide–polyphenol ternary complexes, and the Fmoc-FRGDF/HA hydrogel system demonstrates a superior performance as a delivery vehicle for maintaining quercetin’s bioactivity, thereby establishing a multifunctional platform for bioactive agent encapsulation and controlled release. Full article
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53 pages, 5030 KiB  
Review
Molecular Engineering of Recombinant Protein Hydrogels: Programmable Design and Biomedical Applications
by He Zhang, Jiangning Wang, Jiaona Wei, Xueqi Fu, Junfeng Ma and Jing Chen
Gels 2025, 11(8), 579; https://doi.org/10.3390/gels11080579 - 26 Jul 2025
Viewed by 703
Abstract
Recombinant protein hydrogels have emerged as transformative biomaterials that overcome the bioinertness and unpredictable degradation of traditional synthetic systems by leveraging genetically engineered backbones, such as elastin-like polypeptides, SF, and resilin-like polypeptides, to replicate extracellular matrix (ECM) dynamics and enable programmable functionality. Constructed [...] Read more.
Recombinant protein hydrogels have emerged as transformative biomaterials that overcome the bioinertness and unpredictable degradation of traditional synthetic systems by leveraging genetically engineered backbones, such as elastin-like polypeptides, SF, and resilin-like polypeptides, to replicate extracellular matrix (ECM) dynamics and enable programmable functionality. Constructed through a hierarchical crosslinking strategy, these hydrogels integrate reversible physical interactions with covalent crosslinking approaches, collectively endowing the system with mechanical strength, environmental responsiveness, and controlled degradation behavior. Critically, molecular engineering strategies serve as the cornerstone for functional precision: domain-directed self-assembly exploits coiled-coil or β-sheet motifs to orchestrate hierarchical organization, while modular fusion of bioactive motifs through genetic encoding or site-specific conjugation enables dynamic control over cellular interactions and therapeutic release. Such engineered designs underpin advanced applications, including immunomodulatory scaffolds for diabetic wound regeneration, tumor-microenvironment-responsive drug depots, and shear-thinning bioinks for vascularized bioprinting, by synergizing material properties with biological cues. By uniting synthetic biology with materials science, recombinant hydrogels deliver unprecedented flexibility in tuning physical and biological properties. This review synthesizes emerging crosslinking paradigms and molecular strategies, offering a framework for engineering next-generation, adaptive biomaterials poised to address complex challenges in regenerative medicine and beyond. Full article
(This article belongs to the Special Issue Recent Advances in Protein Gels)
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19 pages, 3200 KiB  
Article
Polyphosphoramidate Glycohydrogels with Biorecognition Properties and Potential Antibacterial Activity
by Zornica Todorova, Oyundari Tumurbaatar, Violeta Mitova, Neli Koseva, Iva Ugrinova, Penka Petrova and Kolio Troev
Molecules 2025, 30(15), 3140; https://doi.org/10.3390/molecules30153140 - 26 Jul 2025
Viewed by 245
Abstract
In the present study, for the first time, a biodegradable and non-toxic polyphosphoramidate glycohydrogel (PPAGHGel) was prepared by crosslinking a polyphosphoramidate glycoconjugate (PPAG) with hexamethylene diisocyanate (HMDI) under mild conditions. Poly(oxyethylene H-phosphonate) (POEHP) was used as a precursor and was converted into PPAG [...] Read more.
In the present study, for the first time, a biodegradable and non-toxic polyphosphoramidate glycohydrogel (PPAGHGel) was prepared by crosslinking a polyphosphoramidate glycoconjugate (PPAG) with hexamethylene diisocyanate (HMDI) under mild conditions. Poly(oxyethylene H-phosphonate) (POEHP) was used as a precursor and was converted into PPAG via the Staudinger reaction with glucose-containing azide (2-p-azidobenzamide-2-deoxy-1,3,4,6-tetra-O-trimethylsilyl-α-D-glucopyranose). Then, crosslinking of PPAG was performed to yield PPAGHGel, which was thoroughly characterized. The gel showed a gel fraction of 83%, a swelling degree of 1426 ± 98%, and G″ = 1560 ± 65 Pa. The gel was fully degraded by alkaline phosphatase (400 U/L, pH 9) in 19 days, while hydrolytically, up to 52% degradation was observed under similar conditions. Multivalent studies of the obtained hydrogel with lectin–Concanavalin A were performed. PPAGHGel binds 92% of Concanavalin A within 24 h and the complex remains stable until the amount of glucose reaches 0.3 mM. PPAGHGel acts as a stabilizer for silver nanoparticles (12 nm). SEM shows pores measuring 10 µm (surface) and 0.1 mm (interior) with capillary channels, confirming the gel’s suitability for biosensors, drug delivery, or wound dressings. The cytotoxic (IC50) and cell-adhesive properties of the obtained hydrogel were investigated on human cell lines (HeLa). Antibacterial activity tests were also performed with gel containing silver nanoparticles against skin-associated pathogenic bacteria. The results show that PPAGHGel possesses excellent biocompatibility, non-adhesive properties and antibacterial activity. Full article
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80 pages, 962 KiB  
Review
Advancements in Hydrogels: A Comprehensive Review of Natural and Synthetic Innovations for Biomedical Applications
by Adina-Elena Segneanu, Ludovic Everard Bejenaru, Cornelia Bejenaru, Antonia Blendea, George Dan Mogoşanu, Andrei Biţă and Eugen Radu Boia
Polymers 2025, 17(15), 2026; https://doi.org/10.3390/polym17152026 - 24 Jul 2025
Viewed by 963
Abstract
In the rapidly evolving field of biomedical engineering, hydrogels have emerged as highly versatile biomaterials that bridge biology and technology through their high water content, exceptional biocompatibility, and tunable mechanical properties. This review provides an integrated overview of both natural and synthetic hydrogels, [...] Read more.
In the rapidly evolving field of biomedical engineering, hydrogels have emerged as highly versatile biomaterials that bridge biology and technology through their high water content, exceptional biocompatibility, and tunable mechanical properties. This review provides an integrated overview of both natural and synthetic hydrogels, examining their structural properties, fabrication methods, and broad biomedical applications, including drug delivery systems, tissue engineering, wound healing, and regenerative medicine. Natural hydrogels derived from sources such as alginate, gelatin, and chitosan are highlighted for their biodegradability and biocompatibility, though often limited by poor mechanical strength and batch variability. Conversely, synthetic hydrogels offer precise control over physical and chemical characteristics via advanced polymer chemistry, enabling customization for specific biomedical functions, yet may present challenges related to bioactivity and degradability. The review also explores intelligent hydrogel systems with stimuli-responsive and bioactive functionalities, emphasizing their role in next-generation healthcare solutions. In modern medicine, temperature-, pH-, enzyme-, light-, electric field-, magnetic field-, and glucose-responsive hydrogels are among the most promising “smart materials”. Their ability to respond to biological signals makes them uniquely suited for next-generation therapeutics, from responsive drug systems to adaptive tissue scaffolds. Key challenges such as scalability, clinical translation, and regulatory approval are discussed, underscoring the need for interdisciplinary collaboration and continued innovation. Overall, this review fosters a comprehensive understanding of hydrogel technologies and their transformative potential in enhancing patient care through advanced, adaptable, and responsive biomaterial systems. Full article
21 pages, 2144 KiB  
Article
In Vitro Release and In Vivo Study of Recombinant TGF-β and EGCG from Dual Self-Cross-Linked Alginate-Di-Aldehyde In Situ Injectable Hydrogel for the Repair of a Degenerated Intervertebral Disc in a Rat Tail
by Bushra Begum, Seema Mudhol, Baseera Begum, Syeda Noor Madni, Sharath Honganoor Padmanabha, Vazir Ashfaq Ahmed and N. Vishal Gupta
Gels 2025, 11(8), 565; https://doi.org/10.3390/gels11080565 - 22 Jul 2025
Viewed by 266
Abstract
Background and Objective: Intervertebral disc degeneration (IVDD) is a leading cause of lower back pain with limited regenerative treatments. Among emerging regenerative approaches, growth factor-based therapies, such as recombinant human transforming growth factor-beta (Rh-TGF-β), have shown potential for disc regeneration but are [...] Read more.
Background and Objective: Intervertebral disc degeneration (IVDD) is a leading cause of lower back pain with limited regenerative treatments. Among emerging regenerative approaches, growth factor-based therapies, such as recombinant human transforming growth factor-beta (Rh-TGF-β), have shown potential for disc regeneration but are hindered by rapid degradation and uncontrolled release by direct administration. Additionally, mechanical stress elevates heat shock protein 90 (HSP-90), impairing cell function and extracellular matrix (ECM) production. This study aimed to investigate a dual self-cross-linked alginate di-aldehyde (ADA) hydrogel system for the sustained delivery of Rh-TGF-β and epigallocatechin gallate (EGCG) to enhance protein stability, regulate release, and promote disc regeneration by targeting both regenerative and stress-response pathways. Methods: ELISA and UV-Vis spectrophotometry assessed Rh-TGF-β and EGCG release profiles. A rat tail IVDD model was established with an Ilizarov-type external fixator for loading, followed by hydrogel treatment with or without bioactive agents. Disc height, tissue structure, and protein expression were evaluated via radiography, histological staining, immunohistochemistry, and Western blotting. Results: The hydrogel demonstrated a biphasic release profile with 100% Rh-TGF-β released over 60 days and complete EGCG release achieved within 15 days. Treated groups showed improved disc height, structural integrity, and proteoglycan retention revealed by histological analysis and elevated HSP-90 expression by immunohistochemistry. In contrast, Western blot analysis confirmed that EGCG effectively downregulated HSP-90 expression, suggesting a reduction in mechanical stress-induced degeneration. Conclusions: ADA hydrogel effectively delivers therapeutic agents, offering a promising strategy for IVDD treatment. Full article
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31 pages, 5930 KiB  
Article
A Novel Microencapsulated Bovine Recombinant Interferon Tau Formulation for Luteolysis Modulation in Cattle
by Emilio Lamazares, Aleikar Vásquez, Kelly Gancino, Felipe Sandoval, Javiera Yáñez-Torres, Miguel A. Gutierrez-Reinoso, Manuel García-Herreros, Paula Gädicke, Ignacio Cabezas, Florence Hugues, Thelvia I. Ramos, Frank Camacho, Karel Mena-Ulecia and Jorge R. Toledo
Biomolecules 2025, 15(7), 1009; https://doi.org/10.3390/biom15071009 - 14 Jul 2025
Viewed by 435
Abstract
Early embryonic loss is a major cause of reproductive inefficiency in cattle, primarily due to premature luteolysis. Interferon tau (IFN-τ), secreted by the trophoblast, plays a critical role in maternal recognition of pregnancy by maintaining corpus luteum function. However, its practical application has [...] Read more.
Early embryonic loss is a major cause of reproductive inefficiency in cattle, primarily due to premature luteolysis. Interferon tau (IFN-τ), secreted by the trophoblast, plays a critical role in maternal recognition of pregnancy by maintaining corpus luteum function. However, its practical application has been limited by its rapid degradation and short half-life in vivo. Here, we developed a novel formulation of recombinant bovine IFN-τ, combining chitosan-based microencapsulation with starch–chitosan hydrogel delivery, enabling sustained intrauterine release. This dual-delivery strategy offers a significant improvement over conventional IFN-τ administration methods that rely on repeated intrauterine infusions of soluble protein. The rbIFN-τ was expressed in Pichia pastoris, purified to 90.1% homogeneity, and structurally validated via homology modeling and molecular docking, confirming its interaction with type I interferon receptors. The encapsulated formulation retained antiviral activity, stimulated transcription of interferon-stimulated genes (PKR, OAS1, OAS2), and showed sustained release in vitro for up to 26 days. In vivo evaluation demonstrated safety and biological efficacy, with treated cattle showing inhibited luteolysis, sustained serum progesterone levels, and preserved corpus luteum integrity. This formulation represents a promising biotechnological approach to improve reproductive efficiency through a long-acting, species-specific IFN-τ delivery system. Full article
(This article belongs to the Section Bio-Engineered Materials)
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26 pages, 7157 KiB  
Article
Succinimidyl Alginate-Modified Fibrin Hydrogels from Human Plasma for Skin Tissue Engineering
by Ana Matesanz, Raúl Sanz-Horta, Alberto Gallardo, Cristina Quílez, Helmut Reinecke, Pablo Acedo, Diego Velasco, Enrique Martínez-Campos, José Luis Jorcano and Carlos Elvira
Gels 2025, 11(7), 540; https://doi.org/10.3390/gels11070540 - 11 Jul 2025
Viewed by 290
Abstract
Plasma-derived fibrin hydrogels are widely used in tissue engineering because of their excellent biological properties. Specifically, human plasma-derived fibrin hydrogels serve as 3D matrices for autologous skin graft production, skeletal muscle repair, and bone regeneration. Nevertheless, for advanced applications such as in vitro [...] Read more.
Plasma-derived fibrin hydrogels are widely used in tissue engineering because of their excellent biological properties. Specifically, human plasma-derived fibrin hydrogels serve as 3D matrices for autologous skin graft production, skeletal muscle repair, and bone regeneration. Nevertheless, for advanced applications such as in vitro skin equivalents and engineered grafts, the intrinsic limitations of native fibrin hydrogels in terms of long-term mechanical stability and resistance to degradation need to be addressed to enhance the usefulness and application of these hydrogels in tissue engineering. In this study, we chemically modified plasma-derived fibrin by incorporating succinimidyl alginate (SA), a version of alginate chemically modified to introduce reactive succinimidyl groups. These NHS ester groups (N-hydroxysuccinimide esters), attached to the alginate backbone, are highly reactive toward the primary amine groups present in plasma proteins such as fibrinogen. When mixed with plasma, the NHS groups covalently bond to the amine groups in fibrin, forming stable amide linkages that reinforce the fibrin network during hydrogel formation. This chemical modification improved mechanical properties, reduces contraction, and enhanced the stability of the resulting hydrogels. Hydrogels were prepared with a final fibrinogen concentration of 1.2 mg/mL and SA concentrations of 0.5, 1, 2, and 3 mg/mL. The objective was to evaluate whether this modification could create a more stable matrix suitable for supporting skin tissue development. The mechanical and microstructure properties of these new hydrogels were evaluated, as were their biocompatibility and potential to create 3D skin models in vitro. Dermo-epidermal skin cultures with primary human fibroblast and keratinocyte cells on these matrices showed improved dermal stability and better tissue structure, particularly SA concentrations of 0.5 and 1 mg/mL, as confirmed by H&E (Hematoxylin and Eosin) staining and immunostaining assays. Overall, these results suggest that SA-functionalized fibrin hydrogels are promising candidates for creating more stable in vitro skin models and engineered skin grafts, as well as for other types of engineered tissues, potentially. Full article
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