Search Results (335)

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

Casein, the main phosphoprotein in milk, has a multifaceted molecular structure and unique physicochemical properties that make it a viable candidate for biomedical use, particularly in wound healing. This review presents a concise analysis of casein’s structural composition that comprises its hydrophobic and hydrophilic nature, calcium phosphate nanocluster structure, and its response to different pH, temperature, and ionic conditions. These characteristics have direct implications for its colloidal stability, including features such as gelation, swelling capacity, and usability as a biomaterial in tissue engineering. This review also discusses industrial derivatives and recent advances in casein biomaterials based on different fabrication types such as hydrogels, electrospun fibres, films, and advanced systems. Furthermore, casein dressings’ functional and biological attributes have shown remarkable exudate absorption, retention of moisture, biocompatibility, and antimicrobial and anti-inflammatory activity in both in vivo and in vitro studies. The gathered evidence highlights casein’s versatile bioactivity and dynamic molecular properties, positioning it as a promising platform to address advanced wound dressing challenges. Full article

This study aimed to develop a functional powder using whey and milk matrices, leveraging the protective capacity of chia–alginate hydrogels and the advantages of electrohydrodynamic spraying (EHDA), a non-thermal technique suitable for encapsulating probiotic cells under stress conditions commonly encountered in food processing. A hydrogel matrix composed of chia seed mucilage and sodium alginate was used to form a biopolymeric network that protected probiotic cells during processing. The encapsulation efficiency reached 99.0 ± 0.01%, and bacterial viability remained above 9.9 log₁₀ CFU/mL after lyophilization, demonstrating the excellent protective capacity of the hydrogel matrix. Microstructural analysis using confocal laser scanning microscopy (CLSM) revealed well-retained cell morphology and homogeneous distribution within the hydrogel matrix while, in contrast, scanning electron microscopy (SEM) showed spherical, porous microcapsules with distinct surface characteristics influenced by the encapsulation method. Encapsulates were incorporated into beverages flavored with red fruits and pear and subsequently freeze-dried. The resulting powders were analyzed for moisture, protein, lipids, carbohydrates, fiber, and color determinations. The results were statistically analyzed using ANOVA and response surface methodology, highlighting the impact of ingredient ratios on nutritional composition. Raman spectroscopy identified molecular features associated with casein, lactose, pectins, anthocyanins, and other functional compounds, confirming the contribution of both matrix and encapsulants maintaining the structural characteristics of the product. The presence of antioxidant bands supported the functional potential of the powder formulations. Chia–alginate hydrogels effectively encapsulated L. reuteri, maintaining cell viability and enabling their incorporation into freeze-dried beverage powders. This approach offers a promising strategy for the development of next-generation functional food gels with enhanced probiotic stability, nutritional properties, and potential application in health-promoting dairy systems. Full article

Intratumoral injections of macromolecules, such as biologics and immunotherapeutics, show promise in overcoming dose-limiting side effects associated with systemic injections and improve treatment efficacy. However, the retention of injectates in the tumor microenvironment is a major underappreciated challenge. High interstitial pressures and dense tumor architectures create shear forces that rapidly expel low-viscosity solutions post-injection. Injectable hydrogels may address these concerns by providing a viscoelastic delivery vehicle that shields loaded therapies from rapid expulsion from the tumor. A chitosan–glycerol hydrogel was thus developed and characterized with the goal of improving the injection retention of loaded therapeutics. The gelation parameters and mechanical properties of the hydrogel were explored to reveal a shear-thinning gel that is injectable through a 27-gauge needle. Biocompatibility studies demonstrated that the chitosan–glycerol hydrogel was nontoxic. Retention studies revealed significant improvements in the retention of model therapeutics when formulated with the chitosan–glycerol hydrogel compared to less-viscous solutions. Finally, release studies showed that there was a sustained release of model therapeutics of various molecular sizes from the hydrogel. Overall, the chitosan–glycerol hydrogel demonstrated injectability, enhanced retention, biocompatibility, and sustained release of macromolecules, indicating its potential for future clinical use in intratumoral macromolecule delivery. Full article

Traditional hydrogel preparation methods typically require multiple steps and certain external stimuli. In this study, rapid and stable gelation of polyvinyl alcohol (PVA)-tannic acid (TA)-based hydrogels was achieved through the regulation of hydrogen bonds. The cross-linking between PVA and TA is triggered by the evaporation of ethanol. Rheological testing and analysis of the liquid-solid transformation process of the hydrogel were performed. The gelation onset time (GOT) could be tuned from 10 s to over 100 s by adjusting the ethanol content and temperature. The addition of polyhydroxyl components (e.g., glycerol) significantly enhances the hydrogel’s water retention capacity (by 858%) and tensile strain rate (by 723%), while concurrently increasing the gelation time. Further studies have shown that the addition of alkaline substances (such as sodium hydroxide) promotes the entanglement of PVA molecular chains, increasing the tensile strength by 23% and the fracture strain by 41.8%. The experimental results indicate that the optimized PVA-TA hydrogels exhibit a high tensile strength (>2 MPa) and excellent tensile properties (~600%). Moreover, the addition of an excess of weakly alkaline substances (such as sodium acetate) reduces the degree of hydrolysis of PVA, enabling the system to form a hydrogel with extrudable characteristics before the ethanol has completely evaporated. This property allows for patterned printing and thus demonstrates the potential of the hydrogel in 3D printing. Overall, this study provides new insights for the application of PVA-TA based hydrogels in the fields of rapid prototyping and strength optimization. Full article

This comprehensive review explores the expansive design space of network architectures and their significant impact on the mechanical and viscoelastic properties of hydrogel systems. By examining the intricate relationships between molecular structure, network connectivity, and resulting bulk properties, we provide critical insights into rational design strategies for tailoring hydrogel mechanics for specific applications. Recent advances in sequence-defined crosslinkers, dynamic covalent chemistries, and biomimetic approaches have significantly expanded the toolbox for creating hydrogels with precisely controlled viscoelasticity, stiffness, and stress relaxation behavior—properties that are crucial for biomedical applications, particularly in tissue engineering and regenerative medicine. Full article

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

A significant issue in healthcare is the growing prevalence of antibiotic-resistant strains. Therefore, it is necessary to develop strategies for discovering new antibacterial compounds, either by identifying natural products or by designing semisynthetic or synthetic compounds with this property. In this context, a great deal of research has recently been carried out on antimicrobial peptides (AMPs), which are natural, amphipathic, low-molecular-weight molecules that act by altering the cell surface and/or interfering with cellular activities essential for life. Progress is also being made in developing strategies to enhance the activity of these compounds through their association with other molecules. In addition to identifying AMPs, it is essential to ensure that they maintain their integrity after passing through the digestive tract and exhibit adequate activity against their targets. Significant advances are being made in relation to analyzing various types of conjugates and carrier systems, such as nanoparticles, vesicles, hydrogels, and carbon nanotubes, among others. In this work, we review the current knowledge of different types of AMPs, their mechanisms of action, and strategies to improve performance. Full article

Polyvinyl alcohol (PVA) hydrogels have emerged as versatile materials due to their exceptional biocompatibility and tunable mechanical properties, showing great promise for flexible sensors, smart wound dressings, and tissue engineering applications. However, rational design remains challenging due to complex structure–property relationships involving multiple formulation parameters. This study presents an interpretable machine learning framework for predicting PVA hydrogel tensile strain properties with emphasis on mechanistic understanding, based on a comprehensive dataset of 350 data points collected from a systematic literature review. XGBoost demonstrated superior performance after Optuna-based optimization, achieving R² values of 0.964 for training and 0.801 for testing. SHAP analysis provided unprecedented mechanistic insights, revealing that PVA molecular weight dominates mechanical performance (SHAP importance: 84.94) through chain entanglement and crystallization mechanisms, followed by degree of hydrolysis (72.46) and cross-linking parameters. The interpretability analysis identified optimal parameter ranges and critical feature interactions, elucidating complex non-linear relationships and reinforcement mechanisms. By addressing the “black box” limitation of machine learning, this approach enables rational design strategies and mechanistic understanding for next-generation multifunctional hydrogels. Full article

The development of printable, biocompatible, biodegradable, and cost-effective bioinks, or biomaterial inks, remains a focal point in extrusion-based bioprinting research. In this study, fish gelatin (FG) was reinforced with microcrystalline cellulose (MCC) to formulate biomaterial inks. These FG/MCC composite inks were fabricated into 3D scaffolds using an extrusion bioprinter. The influence of MCC concentration on printability was systematically evaluated. Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) analyses confirmed the formation of hydrogen bonds between MCC and FG, indicating molecular-level interactions. Notably, MCC incorporation enhanced the rheological properties of the ink and significantly improved the compressive strength of printed scaffolds. Furthermore, MCC content modulated key scaffold characteristics, including porosity, degradation rate, swelling behavior, and microarchitecture. These findings demonstrate that FG/MCC composite hydrogels exhibit optimal properties for extrusion-based 3D bioprinting, offering a promising platform for tissue engineering applications. Full article

Whey protein isolate (WPI) hydrogel is a promising candidate as a biomaterial for tissue engineering. Previously, WPI hydrogels containing poly-γ-glutamic acid (γ-PGA) with a molecular weight (MW) of 440 kDa demonstrated potential as scaffolds for bone tissue engineering. Here, the study compares different γ-PGA preparations of differing MW. WPI-γ-PGA hydrogels containing 40% WPI and 0%, 2.5%, 5%, 7.5%, and 10% γ-PGA were synthesised. Three γ-PGA MWs were compared, namely 10 kDa, 700 kDa, and 1100 kDa. Evidence of successful γ-PGA incorporation was demonstrated by scanning electron microscopy and Fourier transform infrared spectroscopy. Increasing γ-PGA concentration significantly improved the swelling potential of the hydrogels, as demonstrated by ratio mass increases of between 85 and 90% for each 10% variable group. Results suggested that γ-PGA delayed enzymatic proteolysis, potentially decreasing the rate of degradation. The addition of γ-PGA significantly decreased the Young’s modulus and compressive strength of hydrogels. Dental pulp mesenchymal stem cells proliferated on all hydrogels. The highest cellular growth was observed for the WPI-700 kDa γ-PGA group. Additionally, superior cell attachment was observed on all WPI hydrogels containing γ-PGA compared to the WPI control. These results further suggest the potential of WPI hydrogels containing γ-PGA as biomaterials for bone tissue engineering. Full article

Hydrogels are three-dimensional network structures composed of hydrophilic polymers that can swell in water and are very similar to soft tissues such as connective tissue or the extracellular matrix. DNA hydrogels are particularly notable for biomedical applications due to their high biocompatibility, physiological stability, molecular recognition, biodegradability, easy functionalization, and low immunogenicity. Based on these advantages, stimuli-responsive DNA hydrogels that have the property of reversibly changing their structure in response to various microenvironments or molecules are attracting attention as smart nanomaterials that can be applied to biosensing and material transfer, such as in the case of cells and drugs. As DNA nanotechnology advances, DNA can be hybridized with a variety of nanomaterials, from inorganic nanomaterials such as gold nanoparticles (AuNPs) and quantum dots (QDs) to synthetic polymers such as polyacrylamide (PAAm) and poly(N-isopropylacrylamide) (pNIPAM). These hybrid structures exhibit various optical and chemical properties. This review discusses recent advances and remaining challenges in biomedical applications of stimuli-responsive smart DNA hydrogel-based systems. It also highlights various types of hybridized DNA hydrogel, explores various response mechanism strategies of stimuli-responsive DNA hydrogel, and provides insights and prospects for biomedical applications such as biosensing and drug delivery. Full article

A platform of two-component cross-linked hydrogel (cGEL) based on gelatinous peptides and anhydride-containing cross-linkers (oPNMA, oPDMA) is extended for use in peripheral nerve regeneration. Hybrid composites with bio-/chemical cues for enhanced biophysical and biochemical properties were fabricated by covalently grafting small molecular, heterobifunctional amines including the nerve growth factor mimetic LM11A-31 to the oligomeric cross-linkers prior to hydrogel formation. The cytocompatibility and growth-supportive conditions within the matrix are confirmed for pristine and modified hydrogels using L929 mouse fibroblasts and human adipose-derived stem cells (hASCs). For hASCs, cell behavior depends on the type of cross-linker and integrated amine. In a subsequent step, neonatal rat Schwann cells (SCs) are seeded on pristine and functionalized cGEL to investigate the materials’ capabilities to support SC growth and morphology. Within all formulations, cell viability, adherence, and cell extension are maintained though the cell elongation and orientation vary compared to the two-dimensional control. It is possible to merge adjustable two-component hydrogels with amines as biochemical signals, leading to improved nervous cell proliferation and activity. This indicates the potential of tunable bioactive cGEL as biomaterials in nerve implants, suggesting their use as a foundational component for nerve conduits. Full article

Glioblastoma (GBM, isocitrate dehydrogenase wild-type) is the most common primary malignant brain tumor in adults and is associated with a severely low survival rate. Treatments offer mere palliation and are ineffective, due, in part, to a lack of understanding of the intricate mechanisms underlying the disease, including the contribution of the tumor microenvironment (TME). Current GBM models continue to face challenges as they lack the critical components and properties required. To address this limitation, we developed innovative and practical three-dimensional (3D) GBM models with structural and mechanical biomimicry and tunability. These models allowed for more accurate emulation of the extracellular matrix (ECM) and vasculature characteristics of the native GBM TME. Additionally, 3D bioprinting was utilized to integrate these complexities, employing a hydrogel composite to mimic the native environment that is known to contribute to tumor cell growth. First, we examined the changes in physical properties that resulted from adjoining hydrogels at diverse concentrations using Fourier-Transform Infrared Spectroscopy (FTIR), compression testing, scanning electron microscopy (SEM), rheological analysis, and degradation analysis. Subsequently, we refined and optimized the embedded bioprinting processes. The resulting 3D GBM models were structurally reliable and reproducible, featuring integrated inner channels and possessing tunable properties to emulate the characteristics of the GBM ECM. Biocompatibility testing was performed via live/dead and AlamarBlue analyses using GBM cells (both commercial cell lines and patient-derived cell lines) encapsulated in the constructs, along with immunohistochemistry staining to understand how ECM properties altered the functions of GBM cells. The observed behavior of GBM cells indicated greater functionality in softer matrices, while the incorporation of hyaluronic acid (HA) into the gelatin methacryloyl (gelMA) matrix enhanced its biomimicry of the native GBM TME. The findings underscore the critical role of TME components, particularly ECM properties, in influencing GBM survival, proliferation, and molecular expression, laying the groundwork for further mechanistic studies. Additionally, the outcomes validate the potential of leveraging 3D bioprinting for GBM modeling, providing a fully controllable environment to explore specific pathways and therapeutic targets that are challenging to study in conventional model systems. Full article

Microcirculation damage, dermal thickening, and difficulty in the spatiotemporal coordination of key platelet factor 4 (CXCL4) and transforming growth factor-β (TGF-β) contribute to the lack of effective treatments for systemic sclerosis (scleroderma, SSc). To address these challenges, we proposed a novel synergistic drug combination of ginsenoside Rk3 (CXCL4 regulator) and metformin (Met, TGF-β regulator) based on molecular docking and developed an ultra-long release, dual-target regulation hydrogel microneedle system (Rk3/Met URS MN). The rapidly dissolving tips of this hydrogel microneedle consisted of polyvinyl alcohol and polyvinylpyrrolidone, and were loaded with polydopamine-coated, coordination-induced self-assembled Rk3/Met nanomedicines. These micro-tips could spatiotemporally synchronize transdermal delivery of the hydrophobic Rk3 and hydrophilic Met, providing ultra-long release for up to 10 days with a single administration. The recombinant collagen CF-1552/oxidized pullulan-based (CAOP) hydrogel backing exhibited skin self-adhesiveness and excellent mechanical properties and could perform localized moisture retention and free radical scavenging at the lesion site. In vitro and in vivo efficacy studies, along with bioinformatics analysis of RNA sequencing, demonstrated that the Rk3/Met URS MN achieved immune modulation, anti-inflammatory effects, angiogenesis promotion, and antifibrosis in SSc through synergistic CXCL4/TGF-β dual-target regulation. Notably, on the 10th day, the dermal thickness decreased from 248.97 ± 21.3 μm to 152.7 ± 18.1 μm, with no significant difference from the normal group, indicating its significant potential in clinical applications in SSc. Full article