Search Results (297)

Hyaluronic acid (HA) hydrogels are promising biomaterials for tissue engineering and drug delivery due to their biocompatibility and biodegradability. The objective of this study was to develop a novel HA-based hydrogel for the controlled release of basic fibroblast growth factor (bFGF) to promote angiogenesis. A series of PEG-grafted HA hydrogels with varying PEG grafting ratios were synthesized and characterized. We evaluated their physicochemical properties, including swelling ratio, cross-linking density, and enzymatic degradation behavior, and assessed their ability to control bFGF release and induce angiogenesis in a mouse model. The results showed that the PEG-grafting ratio significantly affected the gel properties. Notably, the PEG60-graft-HA hydrogel exhibited a higher swelling ratio and more rapid degradation, suggesting a non-uniform and highly porous structure. In vitro release studies confirmed that while PEG5-graft-HA and PEG15-graft-HA gels showed burst release, the PEG60-graft-HA hydrogel demonstrated sustained release of bFGF over time. Furthermore, in vivo experiments revealed a significant increase in angiogenesis with the PEG60-graft-HA hydrogel, likely due to the prolonged release of active bFGF. These findings suggest that PEG-grafted HA hydrogels, particularly those with a higher PEG grafting ratio, are promising biomaterials for the controlled release of growth factors and applications in tissue regeneration. Full article

In this study, non-toxic, biodegradable, and pH-sensitive polyurethane hydrogels (PUs) were prepared by using hexamethylene diisocyanate (HDI), copolymers of є-caprolactone (CL), rac-lactide (LA), and poly(ethylene glycol) (PEG), poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol) (PEO-bPPO-b-PEO), 1,4-butanediol (BD), and L-glutamine (Gln). The CL, LA, and PEG copolymers were obtained in the presence of a new synthesized catalytic system: diethylzinc/ethyl-3,4-dihydroxybenzoate. Obtained PUs were screened for their cytotoxicity, evaluated for their swelling behavior and hydrolytic degradation, and employed as hydrogel pH-responsive anti-cancer drug delivery systems (DDSs). The novel and promising hydrogel DDSs, capable of releasing 5-fluorouracyl (5-FU) and fluorodeoxyuridine (5-fluoro-2′-deoxyuridine, FUdR) in a sustained and controlled manner, were prepared and were nontoxic. Most prepared hydrogel DDSs were found to release anti-cancer drugs with first-order or zero-order kinetics. The drug release mechanism was generally denoted as Fickian or non-Fickian transport. The possibility of controlling the kinetics of drug release by changing the pH of the environment was also observed. The findings indicate that these PU hydrogels are suitable for use as intelligent DDSs for the targeted delivery of 5-FU or FUdR. We expect that the hydrogel DDSs developed will be utilized in the treatment of pancreatic cancer. Full article

Background/Objectives: Understanding the interactions between nanoparticles and mucosal tissues is crucial for the development of advanced drug delivery systems, as the diffusion behavior of nanoparticles through mucus is strongly influenced by their size and surface properties, and the viscoelastic nature of the hydrogel matrix. In this study, we investigated the impact of nanoparticle size, surface charge, and hydrogel crosslinking density on nanoparticle diffusion in a mucus model in vitro. Method: Citrate-stabilized and PEGylated 30 and 100 nm gold nanoparticles were used as a model of nanoparticle and their diffusion through mucus-mimicking mucin-based hydrogels of two different crosslinking densities was assessed. Results: Citrate-stabilized 30 nm nanoparticles demonstrated greater diffusion in hydrogels mimicking native mucus compared to more densely crosslinked ones, reaching approximately 50.3 ± 0.2% diffusion within the first 5 min of the assay. This size-dependent effect was not observed for the 100 nm citrate-stabilized nanoparticles, which showed limited diffusion in both hydrogel types. To confer different surface charge, gold nanoparticles were functionalized by the conjugation of poly(ethylene glycol) (PEG) derivatives of identical molecular weight with different terminal moieties (neutral, and positively and negatively charged) to modulate the surface charge and assess their interaction with the negatively charged mucin matrix. PEGylated particles exhibited significantly greater mobility than their citrate-stabilized counterparts, regardless of size or hydrogel density owing to the muco-penetration effect of PEG. Among PEGylated particles, the neutral and negatively charged 30 nm variants demonstrated higher diffusion than the positively charged ones due to weaker interactions with the negatively charged mucin hydrogel. For the 100 nm particles, the neutral PEGylated nanoparticles exhibited greater diffusion than their positively charged counterparts. Conclusions: Overall findings could provide valuable insights into the more rational design of nanoparticle-based drug delivery systems targeting mucosal tissues. Full article

This study introduces a single-step method to synthesize guar gum-based interpenetrating polymer network (IPN) hydrogels, achieving simultaneous Diels–Alder crosslinking and amoxicillin (AMOX) encapsulation under mild conditions. To evaluate the influence of porogen addition on IPN structure, drug loading and release, twenty-one formulations were developed, including AMOX loading (25% or 40% w/w relative to the polymer) and biocompatible porogens incorporation [polyethylene glycol (PEG) or sucrose at 5%, 10%, or 50% w/w]. All crosslinked IPN hydrogels formed robust gels, unlike non-crosslinked controls. Porogen choice strongly influenced hydrogel performance: PEG quadrupled the swelling index while enhancing storage modulus (up to 10,054 Pa) and complex viscosity (up to 1302 Pa·s), whereas high sucrose concentrations produced soft, ductile networks with critical strains above 20% and swelling indices up to 1895%. All hydrogels released AMOX at levels above MIC₅₀ for H. pylori. PEG-based IPN provided superior drug delivery profiles, with extended AMOX release (t₅₀ up to 15.5 h at pH 5.0), while sucrose-rich matrices exhibited faster burst release and disintegration. Single-step (pre-loading) AMOX during synthesis improved release control compared to post-loading. These findings highlight the potential of one-pot IPN synthesis with porogen modulation offering a promising gastroretentive platforms for sustained AMOX delivery against H. pylori. Full article

Poly(carboxybetaine methacrylate)s (PCBMA) belongs to a class of zwitterionic polymers that offer promising alternatives to polyethylene glycol (PEG) in biomedical applications. This review highlights how the unique zwitterionic structure of PCBMA dictates its strong antifouling behavior, low immunogenicity, and sensitivity to environmental stimuli such as pH and ionic strength. These features make PCBMA promising for designing advanced systems suited for complex biological environments. This review describes PCBMA-based materials—ranging from hydrogels, nanogels, and surface coatings to drug carriers and protein conjugates—and critically evaluates their performance in drug delivery, tissue engineering, diagnostics, and implantable devices. Comparative studies demonstrated that PCBMA consistently outperformed other zwitterionic polymers and PEG in resisting protein adsorption, maintaining bioactivity of conjugated molecules, and ensuring long circulation times in vivo. Molecular dynamics simulations provide additional information into the hydration shells and conformational behaviors of PCBMA in aqueous dispersions. These insights underscore PCBMA’s broad potential as a promising high-performance material for next generation healthcare technologies. Full article

This study focuses on the synthesis and characterization of thermoresponsive hydrogels of poly(lactic acid) (PLA) and poly(ethylene glycol) (PEG), PLA–PEG copolymers, aiming at the targeted and controlled release of deferoxamine (DFO), a clinically applied iron-chelating drug. Triblock (PLA-PEG-PLA) and diblock (mPEG-PLA) copolymers were synthesized using ring-opening polymerization (ROP) with five different PEGs with molecular weights of 1000, 1500, 2000, 4000, and 6000 g/mol and two types of lactide (L-lactide and D-lactide). Emulsions of the polymers in phosphate-buffered saline (PBS) were prepared at concentrations ranging from 10% to 50% w/w to study the sol–gel transition properties of the copolymers. Amongst the synthesized copolymers, only those that demonstrated thermoresponsive sol-to-gel transitions near physiological temperature (37 °C) were selected for further analysis. Structural and molecular confirmation was performed by Nuclear Magnetic Resonance (NMR) and Fourier-transform infrared spectroscopy (FTIR), while the molecular weights were determined via Gel Permeation Chromatography (GPC). The thermal transitions were studied by calorimetry (DSC) and crystallinity via X-ray diffraction (XRD) analysis. DFO-loaded hydrogels were prepared, and their drug release profiles were investigated under simulated physiological conditions (37 °C) for seven days using HPLC analysis. The thermoresponsive characteristics of these systems can offer a promising strategy for injectable drug delivery applications, where micelles serve as drug carriers and undergo in situ gelation, enabling controlled release. This alternative procedure may significantly improve the bioavailability of DFO and enhance patient compliance by addressing key limitations of conventional administration routes. Full article

Human mesenchymal stem cells (hMSCs) and their secreted extracellular vesicles (EVs) are promising therapeutics to treat degenerative or inflammatory diseases such as ischemic stroke and Alzheimer’s disease (AD). hMSC-EVs have the coveted ability to contain therapeutically relevant biomaterials; however, EV biogenesis is sensitive to the culture microenvironment in vitro. Recently, the demand for hMSC-EVs has increased dramatically, highlighting the need for scalable bioreactors for large-scale biomanufacturing. In this study, adipose-derived hMSCs were seeded in 2D plates, an ultralow-attachment (ULA) plates as static aggregates, a novel vertical wheel bioreactor (VWBR) as aggregates, and a spinner flask bioreactor (SFB). EV secretion was quantified and compared using ExtraPEG-based ultracentrifugation and nanoparticle tracking analysis. Compared to the 2D group, significantly higher total EV production and cell productivity in the bioreactors were observed, as well as the upregulation of EV biogenesis genes. Furthermore, there was increased EV production in the VWBR compared to the SFB and the static ULA control. Functional assessments demonstrated that EVs, when delivered via culture medium or hydrogel-based systems, significantly attenuated oxidative stress elevation, suppressed proinflammatory cytokine secretion (e.g., TNF-α) and gene expression, and inhibited nuclear factor kappa-light-chain-enhancer of activated B-cell (NF-κB) activation and neurodegenerative markers across in vitro assays. These findings suggest EV-mediated mitigation of oxidative and inflammatory pathways, potentially through modulation of the NF-κB signaling cascade. This study shows the influence of bioreactor types and their microenvironments on EV secretion in hMSCs and their applications in hMSC-EV production and bioengineering. Full article

Thermoresponsive hydrogels that undergo reversible sol-gel transitions near physiological temperatures are highly attractive for biomedical applications, such as injectable drug delivery and embolization therapies. In this study, a library of polyurethane-based hydrogels was synthesized via step-growth polymerization using polyethylene glycol (PEG) of varying molecular weights, different diisocyanates, and a series of functional diols derived from diethanolamine with increasing hydrophobicity. The resulting polymers exhibited sol–gel transition behaviors without the need for external crosslinkers, relying solely on non-covalent interactions. The thermal responsiveness was systematically investigated using UV–Vis turbidimetry, and the cloud point temperature (T_CP) was found to be tunable within a range of 26–49 °C by modulating the monomer composition. Statistical modeling identified PEG molecular weight and diol structure as the primary determinants of T_CP, while diisocyanate type and diol-to-PEG ratio had negligible effects. Only diethanolamine (DEA)-based polymers formed stable hydrogels above a critical gelation temperature (LCGT), attributed to enhanced intermolecular interactions via free amine groups. In vitro degradation assays confirmed good hydrolytic stability under physiological conditions over four weeks, with degradation profiles strongly influenced by the PEG chain length and hydrophobic content. These findings establish a structure–property framework for the rational design of injectable, thermoresponsive polyurethane hydrogels with tailored sol–gel behavior for biomedical applications. Full article

Accurate intraoperative localization of deep-seated lesions remains a major challenge in minimally invasive procedures such as laparoscopic and robotic surgeries. Current marking strategies—including ink tattooing and metallic clips—are limited by dye diffusion, or poor intraoperative visibility. To address these issues, we developed and evaluated four thermosensitive injectable hydrogel systems incorporating indocyanine green-human serum albumin (ICG-HSA) complexes: (1) hexanoyl glycol chitosan (HGC), (2) Pluronic F-127, (3) PCL–PEG–PCL, and (4) PLA–PEG–PLA. All hydrogel formulations exhibited sol–gel transitions at physiological temperatures, facilitating in situ dye entrapment and prolonged fluorescence retention. In vivo fluorescence imaging revealed that HGC and Pluronic F-127 hydrogels retained signals for up to five and two days, respectively. In contrast, polyester-based hydrogels (PCL–PEG–PCL and PLA–PEG–PLA) preserved fluorescence for up to 21–30 days. PLA–PEG–PLA showed the highest signal-to-background ratios and sustained intensity, while PCL–PEG–PCL also achieved long-term retention. These findings suggest that thermosensitive hydrogels incorporating ICG-HSA complexes represent promising tissue marker platforms for real-time, minimally invasive, and long-term fluorescence-guided lesion tracking. Full article

During drilling operations, lost circulation frequently occurs, leading to significant loss of drilling fluids which causes environmental damage and increasing drilling costs. To address the problem of fracture plugging, gel materials have emerged as an ideal solution due to stable physicochemical properties and excellent environmental compatibility. However, most existing gels exhibit poor stability and low mechanical strength under high-temperature conditions. To overcome these limitations, high-temperature-resistant phase-conversion stiffened dual-network hydrogel for oil-based drilling fluids was developed. Phase-conversion was realized by immersing synthesized double-network hydrogel in ethylene glycol (EG), polyethylene glycol (PEG), and glycerol (Gly), optimizing and enhancing its mechanical properties, followed by plugging performance evaluations. Experimental results demonstrated that the phase-conversion stiffened gels achieved significantly improved compressive strength and plugging efficiency at elevated temperature. The GC-MS results indicated that dehydration and reagent exchange occurred during immersion, with change in the solid content of the sample. After being treated by white oil at high temperature, the oil phase almost replaced the water phase in the gel. The results of ATR-IR confirmed the formation of hydrogen bonds in the gel. TGA data revealed that PEG enhanced the thermal stability of the gel, EG negatively affected thermal stability, and Gly had negligible influence. The enhancement in gel strength primarily stems from the increase in solid content caused by phase transformation. Dehydration and multiple hydrogen bonds formed between organic reagent molecules and polymer chains in the gel have a synergistic enhancement effect. Full article

Background/Objectives: Metrnl (Meteorin-like), a secreted protein identified in our lab, has been shown to promote wound healing in mice. However, current therapeutic strategies and the underlying mechanisms remain incompletely understood. This study aimed to (1) develop a recombinant human Metrnl (hMetrnl) hydrogel formulation for topical delivery, and (2) elucidate its molecular mechanism in wound repair. Methods: hMetrnl was dispersed in a thermosensitive PLGA-PEG-PLGA hydrogel (hMet-PPP) and applied topically to full-thickness skin wounds in male C57BL/6 mice. A large initial dose was administered on the day of injury, followed by a lower maintenance dose regimen. Mechanistic studies were performed using molecular/cellular assays to assess the effects of hMetrnl. Results: Administration of hMet-PPP significantly accelerated wound healing, reducing the initial wound area and shortening the overall recovery time. hMetrnl transmits signals to endothelial cells via the KIT receptor tyrosine kinase (C-Kit), a membrane receptor, thereby initiating a dual regulatory mechanism involving eNOS to promote angiogenesis: (1) rapid activation of eNOS activity within 30 min through the PI3K/AKT signaling pathway; and (2) suppression of proteasomal and lysosomal eNOS degradation, resulting in enhanced eNOS expression and prolonged functional activity under sustained treatment. Conclusions: Topical hMet-PPP administration represents a promising therapeutic strategy for enhancing early-stage wound healing. hMetrnl exerts its biological effects through C-Kit, which mediates dual regulation of eNOS, both activation and stabilization, providing a mechanistic basis for its potent angiogenic properties. These findings uncover a novel Metrnl mechanism with potential implications for the development of therapies targeting vascular dysfunction and tissue repair. Full article

Functional recovery after traumatic brain injury (TBI) is hindered by progressive neurodegeneration resulting from neuroinflammation and other secondary injury processes. Dexamethasone (DX), a synthetic glucocorticoid, has been shown to reduce inflammation, but its systemic administration can cause a myriad of other medical issues. We aim to provide a local, sustained treatment of DX for TBI. Previously, we demonstrated that PEG-bis-AA/HA-DXM hydrogels composed of polyethyleneglycol-bis-(acryloyloxy acetate) (PEG-bis-AA) and dexamethasone-conjugated hyaluronic acid (HA-DXM) reduced secondary injury and improved motor functional recovery at 7 days post-injury (DPI) in a rat moderate controlled cortical impact (CCI) TBI model. In this study, we evaluated the effect of PEG-bis-AA/HA-DXM hydrogel on cognitive function and secondary injury at 14 DPI. Immediately after injury, hydrogel disks were placed on the surface of the injured cortex. Cognitive function was evaluated using the Morris Water Maze test, and secondary injury was evaluated by histological analysis. The hydrogel treatment group demonstrated significantly shorter latency to target, decreased distance to find the hidden target, increased number of target crossings, increased number of entries to the platform zone, and decreased latency to first entry of target zone compared to untreated TBI rats for probe test. We also observed reduced lesion volume, inflammatory response, and apoptosis in the hydrogel treatment group compared to the untreated TBI group. Full article

The cryopreservation of three-dimensional (3D) biofabricated constructs is a key enabler for their clinical application in regenerative medicine. Unlike two-dimensional (2D) cultures, 3D systems such as encapsulated cell spheroids, molded hydrogels, and bioprinted tissues present specific challenges related to cryoprotectant (CPA) diffusion, thermal gradients, and ice formation during freezing and thawing. This review examines the current strategies for preserving 3D constructs, focusing on the role of biomaterials as cryoprotective matrices. Natural polymers (e.g., hyaluronic acid, alginate, chitosan), protein-based scaffolds (e.g., silk fibroin, sericin), and synthetic polymers (e.g., polyethylene glycol (PEG), polyvinyl alcohol (PVA)) are evaluated for their ability to support cell viability, structural integrity, and CPA transport. Special attention is given to cryoprotectant systems that are free of dimethyl sulfoxide (DMSO), and to the influence of hydrogel architecture on freezing outcomes. We have compared the efficacy and limitations of slow freezing and vitrification protocols and review innovative approaches such as temperature-controlled cryoprinting, nano-warming, and hybrid scaffolds with improved cryocompatibility. Additionally, we address the regulatory and manufacturing challenges associated with developing Good Manufacturing Practice (GMP)-compliant cryopreservation workflows. Overall, this review provides an integrated perspective on material-based strategies for 3D cryopreservation and identifies future directions to enable the long-term storage and clinical translation of engineered tissues. Full article

Postoperative adhesions are a prevalent complication following abdominal surgeries, often leading to significant clinical challenges. This study introduces an innovative solution utilizing a polyethylene glycol (PEG)-based triblock copolymer to form an injectable, self-healing hydrogel aimed at preventing these adhesions. The hydrogel, formulated with temperature-responsive and self-healing properties through the incorporation of poly (N-isopropyl acrylamide) (PNIPAM) and anion–pi interactions, was synthesized using reversible addition–fragmentation chain transfer (RAFT) polymerization. The hydrogel’s physical properties, biocompatibility, hemostatic effect, and anti-adhesive capabilities were rigorously tested through in vitro and in vivo experiments involving rat models. It demonstrated excellent biocompatibility, effective tissue adhesion, and robust hemostatic properties. Most notably, it exhibited significant anti-adhesive effects in a rat abdominal wall–cecum model, reducing adhesion formation effectively compared to controls. The PEG-based injectable hydrogel presents a promising approach for postoperative adhesion prevention. Its ability to gel in situ triggered by body heat, coupled with its self-healing properties, provides a substantial advantage in clinical settings, indicating its potential utility as a novel anti-adhesion material. Full article

Due to its sarcoma-derived origin and the associated carcinogenic risks, as well as its lack of tissue-specific extracellular matrix biochemical cues, the use of the injectable gel scaffold Matrigel is generally restricted to research applications. Therefore, the development of new fully synthetic injectable gel scaffolds that exhibit performance comparable to Matrigel is a high priority. In this study, we developed a novel fully synthetic injectable gel scaffold by combining a biodegradable PLGA-PEG-PLGA copolymer, clay nanoparticle LAPONITE®, and L-arginine-loaded metal–organic frameworks (NU-1000) at the nano level. An aqueous solution of the developed hybrid scaffold (PLGA-PEG-PLGA/LAPONITE®/L-Arg@NU-1000) exhibited rapid sol–gel transition at body temperature following simple injection and formed a continuous bulk-sized gel, demonstrating good injectability. Long-term sustained slow release of L-arginine from the resultant gels can be achieved because NU-1000 is a suitable reservoir for L-arginine. PLGA-PEG-PLGA/LAPONITE®/L-Arg@NU-1000 hybrid gels exhibited good compatibility with and promoted the growth of human skeletal muscle satellite cells. Importantly, in vivo experiments using skeletal muscle injury model mice demonstrated that the tissue regeneration efficiency of PLGA-PEG-PLGA/LAPONITE®/L-Arg@NU-1000 gels is higher than that of Matrigel. Specifically, we judged the higher tissue regeneration efficacy of our gels by histological analysis, including MYH3 immunofluorescent staining, H&E staining, and Masson’s trichrome staining. Taken together, these data suggest that novel hybrid hydrogels could serve as injectable hydrogel scaffolds for in vivo tissue engineering and ultimately replace Matrigel. Full article