Search Results (734)

Deep wounds often lead to severe complications such as persistent infection, biofilm formation, and high patient morbidity. While skin injuries can usually be managed with functional dressings, wounds in deep layers without sufficient treatment may serve as primary entry points for bacterial infection, thereby posing a significant life-threatening risk to patients. With the rising prevalence of chronic diseases and an aging population, effective strategies for enhanced wound healing are still in high demand. In this study, an injectable and thermoresponsive hexamethylene diisocyanate–Pluronic F127 copolymer–hyaluronic acid composite hydrogel loaded with polyhexamethylene biguanide (PHMB) and epidermal growth factor (EGF), named PEHHPG, was developed for joint therapy of deep wounds. PEHHPG self-gels at 37 °C and stabilizes both agents in the gel matrix. Based on the results of microbial colony assay and analysis of fibroblast growth kinetics, PEHHPG with ≥200 ppm of PHMB and ≥0.15 μg/mL of EGF can eradicate bacteria and enhance cell proliferation in vitro, illustrating the functionalities of PEHHPG. Given the aforementioned effects, together with the recognized advantages of injectable hydrogels such as wound shape/depth adaptation, low adhesiveness, exudate absorptiveness, and moisture maintenance, the developed PEHHPG is anticipated to be a feasible dressing material for deep wound treatment after further in vivo examinations. Full article

Dissolving microneedles (DMN) could be considered as a minimally invasive alternative for transdermal delivery of naltrexone hydrochloride (NTX). In the present study, DMN patches with smart design were developed via a two-step micromoulding technique. The systems were composed of drug-free polyvinylpyrrolidone (PVP) and polyvinyl alcohol (PVA) blend microneedle tips, combined with a drug-loaded backing layer based on PVP and Poloxamer 407. The influence of polymer concentration in DMN tips and backing-layer composition on morphology, mechanical properties, drug release and permeation was evaluated. Mechanical studies revealed that intermediate polymer concentration (formulation MN-20%/2:1) provided superior structural integrity (13.57 ± 1.43% height reduction after compression) and efficient penetration up to the fourth Parafilm^® layer. Incorporation of NTX into the backing layer allowed for high drug loading, while a 2:1 PVP:P407 ratio provided higher toughness (1806 g/mm) as well as thermoresponsive and controlled drug release. In vitro permeation studies demonstrated significantly enhanced NTX delivery from DMN systems compared to simple matrix patches—an almost 4-fold increase in flux with 56% permeation of NTX up to 8 h. These findings highlight the importance of polymer composition in DMN design and demonstrate the potential of the developed systems as an effective platform for transdermal delivery of NTX. Full article

Background/Objectives: Gliclazide’s limited water solubility restricts its absorption across the gastrointestinal tract and compromises its therapeutic performance. This study developed a thermoresponsive solid dispersion based on the inverted thermoresponsive behavior of poloxamer 188 in propylene glycol. Methods: A solubility study was conducted to select components for the thermoresponsive solid dispersion. An I-optimal mixture design was used to optimize the concentrations of the thermoresponsive solid dispersion components (poloxamer 188, propylene glycol, and labrasol). FTIR and XRD were used to investigate the mechanism underlying the inverted thermoresponsive behavior. Finally, the influence of the thermoresponsive solid dispersion on gliclazide dissolution was evaluated through in vitro dissolution testing. Results: Surfactant screening identified labrasol as the optimal surfactant owing to a superior increase in gliclazide solubility compared to propylene glycol alone (2.29-fold). The optimized thermoresponsive solid dispersion (poloxamer 188, propylene glycol, and labrasol at 13.89, 21.43, and 64.68% w/w, respectively) achieved a drug solubility of 10.68 mg/g and a phase transition temperature of 36 °C. XRD and FTIR confirmed that hydrogen bonding is responsible for the system’s conversion between the solid and liquid states. Compared with raw gliclazide, the optimized formulation demonstrated an 8.4-fold increase in the initial dissolution rate and significantly improved dissolution efficiency from 21.77 ± 4.74% to 74.85 ± 2.33%. Conclusions: The present thermoresponsive solid dispersion provides a green alternative to conventional solid dispersion techniques. It avoids reliance on organic solvents, processing that demands high energy input, and additional post-processing operations. Full article

Background: Overexpression of immune cell populations leads to self-amplifying cytokine loops, contributing to chronic inflammation in both allograft rejection and autoimmune conditions. Tacrolimus (TAC), despite being a potent immunosuppressant, has limitations; its systemic adverse effects include nephrotoxicity, neurotoxicity, and high variability in tissue exposure in patients. Currently available therapeutic options are limited by the lack of targeted and localized drug delivery systems, resulting in ineffective control over drug-release behavior. Moreover, TAC being highly lipophilic poses challenges for formulation development. To address these gaps, this study focuses on developing a thermoresponsive hydrogel platform comprising distinct nanocarriers for localized delivery of TAC. The nanocarriers include nanoemulsion (NE) and micelles as TAC carriers, and their particle sizes are specifically engineered at the nanoscale for differential release behavior and to support immune cell targeting (macrophages and T-cells). Incorporation into a thermoresponsive hydrogel matrix enables it to act as a local depot at the injection site and deliver TAC with a slow, extended-release profile. Methods: TAC was loaded into a coconut-rich lipid-phase-based NE via high-pressure microfluidization. Simultaneously, TAC-loaded micelles were optimized using a full-factorial design of experiments (DoE) and manufactured via the thin-film hydration method. Both nanocarriers were evaluated for long-term colloidal stability assessments. Hydrogels were produced maintaining aseptic conditions for sterile batch production. Rheological characterization was performed to assess sol-gel transition, thermoreversibility, and injectability, and in vitro release studies were conducted to evaluate TAC diffusion from the developed nanoformulations. Results: Developed nanocarriers resulted in distinct particle sizes in NE (80–85 nm) and micelles (15–17 nm) with successful TAC loading maintaining long-term colloidal stability. The developed TAC-loaded dual-nanocarrier hydrogel (Dual-HG) showed thermoresponsive behavior and gelation at 37 °C, forming as a local depot. In vitro release studies showed slow and extended tacrolimus release from hydrogels and demonstrated particle size-dependent release behavior between the NE and micelle. Conclusions: Therefore, our study highlights a novel dual nanocarrier hydrogel platform combining TAC-NE and TAC-micelle for localized delivery. The findings support that nanocarriers can be engineered to modulate drug diffusion behavior. Notably, the dual nanocarrier within a thermoresponsive hydrogel platform can be used to deliver one or multiple drugs locally, minimizing systemic exposure when sustained local immunosuppression is required. The 25 mL scale sterile batch production of hydrogels emphasizes their suitability for future translational applications. Full article

Cell culture is foundational to biomedical advancements, yet its widespread clinical and practical distribution is severely constrained by the high infrastructural costs of cryogenic logistics and the physical stressors of liquid-phase transit. Herein, we propose a proof-of-concept cryogen-free cell transportation strategy leveraging a rapid reversible thermoresponsive collagen (RRTC) hydrogel regulated by simulated body fluid (SBF). Operating via temperature-driven physical network assembly and disassembly rather than chemical crosslinking or chemical modifications, the RRTC system undergoes a rapid sol-to-gel transition within 60 s at 37 °C for efficient cell encapsulation, and completely reverses to a free-flowing sol state within 60 s at 4 °C to facilitate enzyme-free, non-destructive cell retrieval. Using L929 fibroblasts as a standardized benchmarking cell model, the biophysical protection of the matrix was systematically evaluated under both static simulated transit (48 h and 120 h) and real-world trans-city courier transportation (an approximate 50 h round trip via SF Express) within a passively temperature-shield configuration. The SBF-regulated 3D physical confinement successfully shielded cells from manual handling, multi-axis shipping vibrations, and environmental thermal fluctuations. Post-transport evaluations demonstrated that the encapsulated cells maintained a high viability above 90% and a stable recovery yield of approximately 78%, while exhibiting robust subsequent 2D re-adhesion and sustained re-culture capacity. This thermoresponsive matrix provides a potential matrix for short-term cryogen-free cell transportation and post-transport recovery, while further studies using additional cell types, longer transportation periods, and functional assays are required to evaluate its broader applicability. Full article

The swelling-regulated transport properties of modified and cross-linked HPC-based hydrogel formulations containing NaCMC and citric acid were studied as stimuli-responsive polymeric membranes under various conditions, including deionized water. Physiological conditions were simulated by evaluating various pH conditions (1.2, 6.8, and 7.4). The pseudo-second-order kinetic model best described the swelling process, suggesting that both solvent uptake capacity and polymer network relaxation contribute to the extent of swelling. The swelling behavior of the hydrogel formulations was significantly influenced by salt concentration. The modified HPC hydrogel system exhibited stimuli-responsive swelling–switching behavior under saline, water/ethanol, and acidic/basic environments, demonstrating reversible swelling–deswelling cycles. Maximum swelling was observed in water at pH 7.4. In contrast, abrupt deswelling in an ethanol solution at pH 1.2 reduced hydrogel swelling and water uptake. The effect of temperature on the swelling behavior of the hydrogel and its thermo-responsive swelling behavior was also evaluated. Drug release behavior suggested diffusion-mediated release through the swelling hydrogel matrix. These findings suggest that the modified HPC-based hydrogel system may be useful for pH-responsive oral drug delivery applications. Full article

Injectable hydrogels have attracted substantial and rapidly growing interest due to their ability to be administered into cavities of any shape and provide local therapeutic treatment. This study reports the synthesis and characterization of thermosensitive microgels and hydrogels obtained via photoinitiated copolymerization of methacrylated gelatin (GN-MA) and N-isopropylacrylamide (NIPAM) in the absence and presence of N,N′-methylenebisacrylamide (MBA). The effects of monomer concentration, crosslinker content (MBA), and irradiation time on product yield, grafted chain length, and material properties were systematically investigated. Depending on the polymerization conditions, microgel samples exhibited hydrodynamic diameters in the range of 354–1022 nm at 20 °C, which decreased to 183–308 nm upon heating to 40 °C. Freeze-drying of the microgel dispersions resulted in the formation of a porous sponge-like structure with pore sizes of 50–90 µm. Rheological studies of the hydrogel properties demonstrated evident thermoresponsive behavior, with storage moduli (G′) ranging from 20 to 600 Pa, matching the mechanics of certain soft tissues. The hydrogels showed high equilibrium swelling capacity at 20 °C, which was reduced at 40 °C, as well as temperature-dependent moxifloxacin release (38–88% over 6 days) and excellent biocompatibility (>85% cell viability) with human skin fibroblasts. These findings make them promising for biomedical applications such as postoperative cavity filling and local drug delivery. Full article

Background/Objectives: The limited aqueous solubility of therapeutically active drugs remains a significant challenge in their pharmaceutical application. This study presents a novel solid dispersion matrix (NSDM) that utilizes the inverted thermoresponsive behavior of Pluronic F127 to enhance drug dissolution while addressing the industrial and ecological limitations of conventional methods. Methods: For comparative assessment, a solid dispersion formulation of dapagliflozin was formulated using the NSDM approach and three conventional approaches: heat fusion (HFSD), microwave (MWSD), and lyophilization (LPSD). Differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), and X-ray diffraction (XRD) were used to characterize the prepared formulations. In vitro dissolution test was performed to compare the pharmaceutical performance of NSDM against conventional approaches. Results: The NSDM exhibited a unique thermal transition to the liquid state at 32.4 °C. Moreover, the physiological assessment revealed complete liquefaction within 81.7 s. DSC and XRD confirmed amorphization of dapagliflozin in all formulations. In addition, FTIR revealed that dapagliflozin was integrated within the formulation without any chemical interaction with the excipient. Dissolution studies showed remarkable superiority of NSDM, with 97.30 ± 2.26% dissolution efficiency and a mean dissolution time of 2.40 ± 0.80 min. A multi-criteria assessment of ecological impact, worker friendliness, industrial effectiveness, and pharmaceutical performance demonstrated NSDM’s comprehensive advantages. Conclusions: The present approach provides a sustainable paradigm compared to conventional solid dispersion approaches. It eliminates energy-intensive operations and post-processing steps through direct capsule filling. This affords superior pharmaceutical performance while supporting sustainability and industrial applicability. Full article

Stimuli-responsive hydrogels have gained significant attention as one of the most attractive materials for soft robots. Herein, a facile, printable thermo-responsive hydrogel (NL hydrogel) with rapid volume change capability and excellent mechanical properties was developed through the self-assembly of poly(N-isopropylacrylamide) (PNIPAM) and hydrophobic lignin. The lignin and PNIPAM self-assembled into a hierarchical phase-separated structure consisting of lignin-rich dense regions with a bicontinuous morphology and PNIPAM-rich, chain-sparse regions. This unique architecture results in multiscale water channels, enabling an ultrafast dehydration response (expelling 90% of its water within 10 s) and an ultrahigh volume shrinkage of up to 96.4% above its lower critical solution temperature (LCST). The phase separation structure also endows the NL hydrogels with outstanding mechanical properties, achieving tensile stress and strain values exceeding 1 MPa and 500% below the LCST, and approximately 5 MPa and 1500% above the LCST. The responsive speed and mechanical properties of the NL hydrogels surpass those of most reported thermo-responsive hydrogels. The NL hydrogels can be readily printed via direct ink writing into various geometries. The printed NL hydrogels demonstrate thermo-triggered shape morphing, functioning as temperature-controlled actuators with adjustable curvature and as manipulators for capture, wrapping, encapsulation, and switching. Furthermore, the photothermal effect of lignin enables light-controlled actuation of the NL hydrogel. Full article

Oleuropein, the principal secoiridoid phenolic compound of olive leaves (Olea europaea L.), is recognized for its broad-spectrum antimicrobial, antibiofilm, antioxidant, and tissue-regenerative properties. However, its effective local therapeutic application remains challenging due to rapid clearance from the site of administration and limited residence time. In this study, an oleuropein-rich aqueous olive leaf extract was incorporated into a thermoresponsive sol–gel delivery system designed for localized application. The formulation was engineered to remain in a low-viscosity sol state at room temperature and to undergo a temperature-triggered sol-to-gel transition near physiological temperature (~33 °C), enabling in situ gel formation. Oleuropein content was quantified using a validated HPLC method, and the formulation was characterized with respect to physicochemical parameters, thermoreversible gelation behavior, particle size distribution, mechanical properties, and spreadability. Biological performance was evaluated through in vitro cytocompatibility (MTT assay), fibroblast migration (scratch assay), and collagen deposition (Sirius Red staining) in L929 fibroblasts, as well as antibiofilm activity against representative Gram-positive and Gram-negative bacterial strains. The developed sol–gel system demonstrated stable physicochemical characteristics, rapid and reversible thermogelation, suitable mechanical and spreading properties, concentration-dependent inhibition of biofilm formation, and acceptable cytocompatibility within the tested concentration range. Notably, the formulation supported fibroblast viability and collagen-associated responses at optimized concentrations. Overall, the results indicate that the proposed thermoresponsive sol–gel formulation represents a promising strategy for the localized delivery of oleuropein-rich olive leaf extract, combining physicochemical stability with dual wound-healing and antibiofilm functionality. Full article

Current strategies for treating organic dye wastewater are shifting from single-function removal processes and catalytic degradation methods toward more integrated treatment approaches. This study proposes a multifunctional composite integrating adsorption–photodegradation–intelligent recovery for photodegradation and recovery of methylene blue-contaminated wastewater. By optimizing the preparation process to precisely control the pore size and arrangement of the aerogel, a hierarchical porous framework with a high specific surface area is formed, featuring efficient mass transfer and ultra-multiple loading sites. The graphene framework enhances visible-light absorption by optimizing TiO₂ loading, agglomeration behavior and addressing detachable defects through a metal–polyphenol network. After 60 min of illumination, the degradation efficiency exceeds 99.5%, demonstrating superior cycling stability. After 100 cycles, the photocatalytic efficiency remains above 97%, showcasing excellent durability. Furthermore, the in situ polymerized thermoresponsive poly (N-isopropylacrylamide) (PNIPAm) composite exhibits smart responsiveness, enabling reversible temperature-responsive adsorption–desorption behavior within PNIPAm’s LCST range. with an adsorption capacity of 28,000 mg/g at LCST. Heating above LCST desorbs 90.2% of the wastewater, and adsorption stability remains above 98% after 100 thermal cycles, resolving operational challenges in mechanical wastewater recovery. The synergistic integration of an anisotropic porous structure, stable TiO₂ loading, and thermal responsiveness provides an efficient platform for integrated adsorption and recovery. Full article

Human induced pluripotent stem cell (iPSC)-derived brain organoids have emerged as powerful three-dimensional (3D) platforms for modeling human neurodevelopment and neurological disorders. However, the absence of a functional vascular network remains a critical limitation, restricting oxygen and nutrient delivery, impairing metabolic stability, and constraining long-term maturation. Conventional extracellular matrix (ECM) mimetics, such as Matrigel and other static synthetic hydrogels, provide biochemical support but fail to recapitulate the dynamic remodeling that characterizes the developing neurovascular niche. Recent advances in stimuli-responsive hydrogels offer spatiotemporal control over matrix stiffness, degradability, viscoelasticity, and biochemical cue presentation. In this review, we discuss dynamic hydrogel systems within a structure–property–function framework, highlighting how network chemistry and architecture may regulate endothelial sprouting, lumen formation, vascular stabilization, and neurovascular unit maturation in vascularized brain organoid models, based on evidence from both organoid studies and related biomaterial or vascular systems. Photoresponsive, enzyme-cleavable, thermo-responsive, supramolecular, bio-orthogonal click-based, and bioprinted platforms are discussed with emphasis on mechanotransduction, angiocrine signaling, and barrier specialization. Functional outcomes, including trans-endothelial electrical resistance, selective permeability, transporter expression, electrophysiological integration, and sustained perfusion, are discussed alongside translational challenges such as cytocompatibility, oxidative stress, scalability, and regulatory feasibility. Collectively, dynamic hydrogels provide a versatile biomaterial strategy for improving vascularization and aspects of functional maturation in brain organoid models with enhanced physiological relevance. Ultimately, stimuli-responsive hydrogel systems may serve as enabling platforms for engineering vascularized brain organoids and advancing human-relevant neurovascular disease modeling. Full article

Periodontitis is a chronic inflammatory disease marked by the progressive destruction of periodontal tissues, where conventional therapies often fail to maintain adequate drug levels at the target site. This study reports the development and characterization of a thermosensitive gel containing nanostructured lipid carriers (NLC) for controlled local periodontal delivery. Apigenin (AP)-loaded NLC were prepared using AP as active agent and clove essential oil (CEO) as liquid lipid subsequently incorporated into Poloxamer 407 (5–15% w/w) hydrogels. The formulations were evaluated in relation to particle size, morphology, thermal and rheological behavior, mucoadhesion, in vitro release, antibacterial activity, and stability. Optimized nanoscale NLC showed a high entrapment efficiency, and uniform morphology. Raman analysis confirmed successful AP incorporation and homogeneous distribution in the gel without incompatibility. NLC-loaded gels exhibited sol–gel transition at physiological temperature with improved viscoelasticity and enhanced mucoadhesion. The drug release was sustained for 48 h and followed the Korsmeyer–Peppas model, indicating diffusion-based and anomalous transport. The antibacterial assessment demonstrated the pronounced inhibitory activity of the NLC formulations against key periodontal pathogens, with the formulation-dependent modulation of antimicrobial efficacy observed following the gel incorporation. Stability studies showed preserved nanoparticle structure and uniform dispersion. Overall, the thermoresponsive NLC-hydrogel system offers a promising strategy for prolonged, localized periodontal therapy. Full article

Hydrogels are widely investigated as drug carriers for cancer therapy due to their ability to provide sustained release and reduce systemic side effects. In this study, MeBSA–PNIPAm hydrogels were developed as dual-temperature and pH-responsive systems for gastrointestinal delivery of 5-FU. MeBSA was successfully synthesized using glycidyl methacrylate and confirmed by FTIR and ¹H-NMR analyses. Hydrogels with varying MeBSA/NIPA ratios were prepared via redox polymerization. DSC results showed that increasing MeBSA content shifted the phase transition temperature of hydrogels, while TGA analysis revealed enhanced thermal stability with higher MeBSA incorporation. Temperature-dependent swelling experiments further demonstrated that the VPTT slightly shifted depending on the surrounding pH, indicating that the thermoresponsive behavior of the hybrid network is influenced by the pH-dependent charge state of the protein component. Swelling studies performed at 30, 37, and 40 °C and at pH 1.2 and 7.4 confirmed dual-responsive behavior. Drug loading efficiencies above 70% were achieved for all formulations. In vitro release studies at 37 °C demonstrated distinct composition-dependent release profiles. During the first 2 h, all hydrogels exhibited controlled and limited release without burst behavior under acidic conditions. Following the transition to pH 7.4, a composition-dependent increase in drug release was observed. GEL 4 achieved the fastest and highest cumulative release (91%), whereas GEL 1 provided the most sustained release over 72 h (32%). Kinetic analysis indicated diffusion-controlled release, best described by the Weibull and Korsmeyer–Peppas models. Cytocompatibility tests showed that fibroblast viability improved with increasing MeBSA content. Overall, protein-modulated dual-responsive hydrogels offer tunable and biocompatible platforms for stimuli-responsive gastrointestinal drug delivery applications. Full article