Poly Ethylene Glycol Hydrogels Research Articles

Enlightenment the dynamic behavior of norbornene–modified ’click’ 4–arm polyethylene glycol hydrogel: Delving into framework properties and transport properties through molecular dynamics simulations

The thiol-norbornene cross-linked 4-arm Polyethylene Glycol (PEG) ’click’ hydrogel is a synthetic, sustainable, and bio-inspired polymer extensively used in biomedical applications. Experimental techniques are widely used to study this system, whereas all-atom molecular dynamics simulations, which offer insight into the dynamic behaviours of the system, are never used to study this system. Three models of thiol-norbornene cross-linked PEG ’click’ hydrogel and a base PEG hydrogel are crafted. It is immersed in water to study its structural and transport properties. Structural properties are analysed through root-mean-square deviation (RMSD), radial distribution function (RDF), hydrogen bonds (H-bond), and stress–strain behavior. The RMSD reveals that the norbornene component enhances hydrogel stability compared to the base model. The RDF illustrates interactions between oxygen in PEG chains and water. H-bond results underscore PEG’s strong H-bond acceptance. The norbornene-functionalized crosslinked PEG hydrogel displays maximum H-bonding. It demonstrates a superior swelling ratio attributed to freezing and non-freezing water effects, indicating high stability and potential suitability for applications. Mean square displacements (MSD) unveil the diffusion coefficients of the hydrogel. The base hydrogel model shows the diffusive behavior, and the diffusion coefficient is 1.97 × 10-10 m2/s. The base model has the highest MSD value compared to other systems. The thiol-norbornene crosslinked click hydrogel has the highest Young’s modulus, which signifies the stiffness of the material. Findings illuminate thiol-norbornene ’click’ PEG hydrogel behaviour, emphasising chemical cross-linking’s crucial role in advanced biomedical applications.

Space-Confined Amplification for In Situ Imaging of Single Nucleic Acid and Single Pathogen on Biological Samples.

Direct in situ imaging of nucleic acids on biological samples is advantageous for rapid analysis without DNA extraction. However, traditional nucleic acid amplification in aqueous solutions tends to lose spatial information because of the high mobility of molecules. Similar to a cellular matrix, hydrogels with biomimetic 3D nanoconfined spaces can limit the free diffusion of nucleic acids, thereby allowing for ultrafast in situ enzymatic reactions. In this study, hydrogel-based in situ space-confined interfacial amplification (iSCIA) is developed for direct imaging of single nucleic acid and single pathogen on biological samples without formaldehyde fixation. With a polyethylene glycol hydrogel coating, nucleic acids on the sample are nanoconfined with restricted movement, while in situ amplification can be successfully performed. As a result, the nucleic acids are lighted-up on the large-scale surface in 20min, with a detection limit as low as 1 copy/10 cm2. Multiplex imaging with a deep learning model is also established to automatically analyze multiple targets. Furthermore, the iSCIA imaging of pathogens on plant leaves and food is successfully used to monitor plant health and food safety. The proposed technique, a rapid and flexible system for in situ imaging, has great potential for food, environmental, and clinical applications.

Bacteria encapsulation into polyethylene glycol hydrogels using Michael-type addition reactions

AbstractHydrogel materials can be used to integrate bacteria cells into biohybrid systems. Here, we investigate the use of polyethylene glycol-based hydrogels that employ different Michael-type addition crosslinking chemistries, including thiol-acrylate, thiol-vinyl sulfone, and thiol-maleimide click reactions, for covalent hydrogel network formation and bacteria encapsulation. All crosslinking chemistries generated hydrogels that provided stable encapsulation and culture of Bacillus subtilis; however, significant differences in cell viability and cell morphology after encapsulation were identified. Thiol-acrylate hydrogels provided the highest cell viability and favored encapsulation of single cells, while thiol-maleimide hydrogels had the lowest cell viability and favored encapsulation of larger aggregates. These findings demonstrate the impact of crosslinking strategies for encapsulation of microorganisms into hydrogel networks and suggest that thiol-acrylate chemistries are favorable for many applications. Graphical abstract

Electrobiofabrication of antibody sensor interfaces within a 3D printed device yield rapid and robust electrochemical measurements of titer and glycan structure.

We report the integration of 3D printing, electrobiofabrication, and protein engineering to create a device that enables near real-time analysis of monoclonal antibody (mAb) titer and quality. 3D printing was used to create the macroscale architecture that can control fluidic contact of a sample with multiple electrodes for replicate measurements. An analysis "chip" was configured as a "snap-in" module for connecting to a 3D printed housing containing fluidic and electronic communication systems. Electrobiofabrication was used to functionalize each electrode by the assembly of a hydrogel interface containing biomolecular recognition and capture proteins. Specifically, an electrochemical thiol oxidation is used to assemble a thiolated polyethylene glycol hydrogel, that in turn is covalently coupled to either a cysteine-tagged protein G that binds the antibody's Fc region or a lectin that binds the glycans of target mAb analytes. We first show the design, assembly, and testing of the hardware device. Then, we show the transition of a step-by-step sensing methodology (e.g., mix, incubate, wash, mix, incubate, wash, measure) into the current method where functionalization, antibody capture, and assessment are performed in situ and in parallel channels. Both titer and glycan analyses were found to be linear with antibody concentration (to 0.2 mg/L). We further found the interfaces could be reused with remarkably similar results. Because the interface assembly and use are simple, rapid, and robust, we suggest this assessment methodology will be widely applicable, including for other biomolecular process development and manufacturing environments.

Osteogenic differentiation capabilities of multiarm PEG hydrogels: involvement of gel–gel-phase separation in cell differentiation

AbstractThe development of bioactive scaffolds is essential for tissue engineering because of the influence of material physicochemical properties on cellular activities. Recently, we discovered that percolation-induced 4-arm polyethylene glycol (PEG) hydrogels achieved gel–gel phase separation (GGPS), which has tissue affinity in vivo. However, whether the 4-arm structure is the optimal configuration for the use of PEG hydrogels as scaffolds remains unclear. In this study, we investigated the effect of an increased branching factor on GGPS. Compared with the 4-arm PEG hydrogel, the 8-arm PEG hydrogel presented a greater degree of GGPS and increased hydrophobicity. We introduced the RGD sequence into PEG hydrogels to directly assess the biological activity of GGPS, with a particular focus on its effects on the activity of bone-forming osteoblasts. Although the 8-arm PEG hydrogel did not enhance cell adhesion, it enhanced osteoblast differentiation compared with the 4-arm PEG hydrogel. Therefore, the 8-arm PEG hydrogel mediated by GGPS shows promise as a scaffold for osteoblast differentiation and holds potential as a foundation for future advancements in bone tissue engineering.

Engineering a 3D Biomimetic Peptides Functionalized-Polyethylene Glycol Hydrogel Model Cocultured with Endothelial Cells and Astrocytes: Enhancing In Vitro Blood-Brain Barrier Biomimicry.

The blood-brain barrier (BBB) poses a significant challenge for drug delivery and is linked to various neurovascular disorders. In vitro BBB models provide a tool to investigate drug permeation across the BBB and the barrier's response to external injury events. Yet, existing models lack fidelity in replicating the BBB's complexity, hindering a comprehensive understanding of its functions. This study introduces a three-dimensional (3D) model using polyethylene glycol (PEG) hydrogels modified with biomimetic peptides that represent recognition sequences of key proteins in the brain. Hydrogels were functionalized with recognition sequences for laminin (IKVAV) and fibronectin peptides (RGD) and chemically cross-linked with matrix metalloprotease-sensitive peptides (MMPs) to mimic the extracellular matrix of the BBB. Astrocytes and endothelial cells were seeded within and on the surface of the hydrogels, respectively. The barrier integrity was assessed through different tests including transendothelial electrical resistance (TEER), the permeability of sodium fluorescence (Na-F), the permeability of Evan's blue bound to albumin (EBA), and the expression of zonula occluden-1 (ZO-1) in seeded endothelial cells. Hydrogels with a combination of RGD and IKVAV peptides displayed superior performance, exhibiting significantly higher TEER values (55.33 ± 1.47 Ω·cm2) at day 5 compared to other 2D controls including HAECs-monoculture and HAECs-cocultured with NHAs seeded on well inserts and 3D controls including RGD hydrogel and RGD-IKVAV monoculture with HAECs and RGD hydrogel cocultured with HAECs and NHAs. The designed 3D system resulted in the lowest Evan's blue permeability at 120 min (0.215 ± 0.055 μg/mL) compared to controls. ZO-1 expression was significantly higher and formed a relatively larger network in the functionalized hydrogel cocultured with astrocytes and endothelial cells compared to the controls. Thus, the designed 3D model effectively recapitulates the main BBB structure and function in vitro and is expected to contribute to a deeper understanding of pathological CNS angiogenesis and the development of effective CNS medications.

The thawing process in gentamicin and polyethylene glycol hydrogel: The impact of selected parameters on the calculation of activation energy using the methods of Belichmaer and Duswalt

AbstractThe subject of the research conducted by differential scanning calorimetry (DSC) was hydrated mixtures of polyethylene glycol and gentamicin (GEN) in a 1:1 (w/w) ratio. In this way, a system with a particularly high ability to form hydrogen bonds was created. It was postulated that studying the effective activation energy (EA) of the thawing process of diverse hydrated polymer mixtures will indirectly allow for an attempt to assess the distribution of water molecules in the examined material in future studies. This article presents a detailed analysis of the impact of selected parameters on the calculation of EA using the Belichmaer and Duswalt methods. The research focused on assessing how the interpolation method affects the accuracy of results obtained from these techniques. The interpolation method was analyzed in terms of its ability to accurately replicate experimental data. By evaluating the impact of the number of points from the DSC curve used in linear interpolation, a standard deviation from the average value of EA was obtained, respectively: 2.4% for the Belichmaer method and 1.9% for the Duswalt method. The article also shows that by using both methods simultaneously, it is possible to detect the moment when additional endothermic and exothermic reaction activity becomes present in the reaction curve. This allowed for the avoidance of the depletion error. Computer modeling and simulations were used to compare the effectiveness of both techniques in various scenarios. The results showed that the choice of interpolation method and taking into account the depletion error significantly affect the accuracy of calculating EA. The computed activation energy via Duswalt method was EA = 363.32 kJ mol−1 with a standard deviation of 7.07 kJ mol−1 and using the Belichmaer method the EA was 364.81 kJ mol−1, with a standard deviation of 9.10 kJ mol−1.

Symmetry, separation, and stability: Physical properties for effective dosimetric space with a stabilized hyaluronic acid spacer.

The proximity of the rectum to the prostate in radiation therapy (RT) for prostate cancer presents a significant dosimetric challenge, leading to high rectal doses and resulting in detrimental side effects. Perirectal tissue spacing reduces rectal dose and gastrointestinal toxicities by mechanically separating these organs. A variety of materials have been explored for use as rectal spacers, most recently, a stabilized hyaluronic acid (HA) gel, which can be formed into deliberate a shape, and retains the definition of that shape, while remaining flexible, unlike polyethylene glycol (PEG) hydrogels. This study evaluates the dosimetric impact of the spacer, including shape symmetry, the degree of separation at different locations, and the temporal stability of the space. Our goal is to provide physics-informed guidance on the optimal use of this sculptable spacer. A secondary analysis was performed on data from a 13-center prospective randomized trial (NCT04189913), involving 136 patients with centrally-reviewed treatment plans conducted on CT/MR simulation scans before and after receiving HA spacer implants. Patients were treated with 60Gy in 20 fractions to the prostate. For this study, python software was utilized for automated processing of DICOM RTstruct and RTdose files, facilitating detailed analysis of the spacer's impact on anatomical displacement and dosimetric outcomes. Complete dose-volume histograms (DVHs) were reconstructed, and combined into composite population DVHs before and after implant, verified against trial-reported dose points. Patients were divided into similar groups of separation and symmetry, and differences in their composite DVHs were tested for significance. Stability of the spacer was studied by comparing serial MRI images and by computing the distance between contours at four axial planes, at simulation and 3-month follow-up, post RT. The introduction of the HA spacer significantly enhanced rectal sparing, as evidenced by a reduction in the mean rectal integral dose by over 6Gy. High rates of implant symmetry(>95%) were observed, indicating nearly optimal lateral spacer placement. In superior-inferior coverage, this study like many others, saw the spacing largest at the superior extent but becoming more variable inferiorly at the level of the prostate apex. This allowed study of the apex as a specific area for dosimetric concern. Stability assessments confirmed that the spacer maintained its position and dimensions between the simulation and the 3-month post-RT, implying stable geometry during treatment, with only minimal separation changes observed. Statistical analysis using the Kruskal-Wallis test revealed significant correlations of larger separations at the inferior and apical planes with improved dosimetric outcomes, including rV30Gy. The use of a stabilized HA spacer in prostate RT effectively enhances prostate-rectum separation, leading to significant rectal sparing without undesirable dose compromises. This study underscores the role of strategic placement and shape, specifically including>1cm separation from the base down to the prostate apex. When combined with the treatment planning techniques used in the trial to create a steep dosimetric gradient across the spacer, these findings elucidate the dosimetric outcomes that can be expected in the clinical implementation of HA spacer. This is particularly relevant in the evolution of hypofractionated treatment regimens for prostate cancer therapy.

EUS-guided hydrogel injection to separate pancreatic head carcinoma from duodenum for enhanced radiotherapy: Multi-site feasibility study.

Background and study aims The proximity of a pancreas head tumor to the duodenum often limits delivery of an ablative dose of radiation therapy. This study evaluated the feasibility and safety of using an injectable polyethylene glycol (PEG) hydrogel between the head of the pancreas and duodenum. Patients and methods In a multi-site feasibility cohort study of patients with localized pancreatic cancer, PEG hydrogel was injected under endoscopic ultrasound guidance to temporarily position the duodenum away from the pancreas. Procedure characteristics were recorded, including hydrogel volume and space created. Patients were monitored for adverse events (AEs) and radiotherapy toxicity. Results In all six intent-to-treat patients (four with borderline resectable, two with locally advanced disease), the ability to place and visualize PEG hydrogel and create space between the duodenum and the head of the pancreas was successful. There were no procedure-related AEs resulting in radiotherapy delay. There were no device-related AEs and no reports of pancreatitis. Conclusions PEG hydrogel was successfully placed, created space between the duodenum and the head of the pancreas, and was not associated with major toxicity. Enhancing radiotherapy for pancreatic cancer by using PEG hydrogel to create peri-duodenal space could have beneficial implications for treatment and warrants more exploration.

Cellulose fiber derived from sugarcane bagasse and polyethylene glycol/acrylic acid/ branched polyethylenimine-based hydrogel composite prepared by gamma irradiation: A platform for mercury (II) ions adsorption

In this study, cellulose was successfully purified from sugarcane bagasse by alkali treatment and bleaching process. Then, 2-10 wt% of purified cellulose was added into polyethylene glycol and acrylic acid-based hydrogel composite. 25 kGy of gamma irradiation dose was employed to form the gel. With the presence of various cellulose contents, no significant change of functional group was therefore observed. The hydrogel composite was thermally resisted up to 250°C. The microstructure of composite exhibited as an interconnected porosity throughout hydrogel network. Cellulose was located inside hydrogel composite. The gel fraction and porosity for all of composites were reported to be 92-97% and 73-81%, respectively. The swelling behavior was very rapid within initial stage (5 hours) and then, it presented as a plateau region. The presence of purified cellulose significantly offered high dimensional stability. After that, in order to enhance the ability for Hg2+ adsorption, bPEI was coated onto the surface of hydrogel composite. FTIR was employed to evaluate the presence of N-H stretching. At the neutral pH, it defined as an optimal region for adsorption. The efficiency and capacity for Hg2+ adsorption were reported to be 55.17% and 82.94 mg/g in 24 hours, respectively. This was related to the pseudo-second-order kinetic model due to R2 of 0.9941 indicating the chemical adsorption process. Furthermore, EDX analysis confirmed that the existence of Hg was presented onto hydrogel composite surface. It was remarkably noted that purified cellulose from sugarcane bagasse was successfully inserted into hydrogel composite by gamma irradiation technique. It provided a great promise as a platform for mercury ion adsorption.

Soft Polyethylene Glycol Hydrogels Support Human PSC Pluripotency and Morphogenesis.

Lumenogenesis within the epiblast represents a critical step in early human development, priming the embryo for future specification and patterning events. However, little is known about the specific mechanisms that drive this process due to the inability to study the early embryo in vivo. While human pluripotent stem cell (hPSC)-based models recapitulate many aspects of the human epiblast, most approaches for generating these 3D structures rely on ill-defined, reconstituted basement membrane matrices. Here, we designed synthetic, nonadhesive polyethylene glycol (PEG) hydrogel matrices to better understand the role of matrix mechanical cues in iPSC morphogenesis, specifically elastic modulus. First, we identified a narrow range of hydrogel moduli that were conducive to the hPSC viability, pluripotency, and differentiation. We then used this platform to investigate the effects of the hydrogel modulus on lumenogenesis, finding that matrices of intermediate stiffness yielded the most epiblast-like aggregates. Conversely, stiffer matrices impeded lumen formation and apico-basal polarization, while the softest matrices yielded polarized but aberrant structures. Our approach offers a simple, modular platform for modeling the human epiblast and investigating the role of matrix cues in its morphogenesis.

Synthetic biodegradable microporous hydrogels for in vitro 3D culture of functional human bone cell networks

Generating 3D bone cell networks in vitro that mimic the dynamic process during early bone formation remains challenging. Here, we report a synthetic biodegradable microporous hydrogel for efficient formation of 3D networks from human primary cells, analysis of cell-secreted extracellular matrix (ECM) and microfluidic integration. Using polymerization-induced phase separation, we demonstrate dynamic in situ formation of microporosity (5–20 µm) within matrix metalloproteinase-degradable polyethylene glycol hydrogels in the presence of living cells. Pore formation is triggered by thiol-Michael-addition crosslinking of a viscous precursor solution supplemented with hyaluronic acid and dextran. The resulting microporous architecture can be fine-tuned by adjusting the concentration and molecular weight of dextran. After encapsulation in microporous hydrogels, human mesenchymal stromal cells and osteoblasts spread rapidly and form 3D networks within 24 hours. We demonstrate that matrix degradability controls cell-matrix remodeling, osteogenic differentiation, and deposition of ECM proteins such as collagen. Finally, we report microfluidic integration and proof-of-concept osteogenic differentiation of 3D cell networks under perfusion on chip. Altogether, this work introduces a synthetic microporous hydrogel to efficiently differentiate 3D human bone cell networks, facilitating future in vitro studies on early bone development.

Granular Biphasic Colloidal Hydrogels for 3D Bioprinting.

Granular hydrogels composed of hydrogel microparticles are promising candidates for 3D bioprinting due to their ability to protect encapsulated cells. However, to achieve high print fidelity, hydrogel microparticles need to jam to exhibit shear-thinning characteristics, which is crucial for 3D printing. Unfortunately, this overpacking can significantly impact cell viability, thereby negating the primary advantage of using hydrogel microparticles to shield cells from shear forces. To overcome this challenge, a novel solution: a biphasic, granular colloidal bioink designed to optimize cell viability and printing fidelity is introduced. The biphasic ink consists of cell-laden polyethylene glycol (PEG) hydrogel microparticles embedded in a continuous gelatin methacryloyl (GelMA)-nanosilicate colloidal network. Here, it is demonstrated that this biphasic bioink offers outstanding rheological properties, print fidelity, and structural stability. Furthermore, its utility for engineering complex tissues with multiple cell types and heterogeneous microenvironments is demonstrated, by incorporating β-islet cells into the PEG microparticles and endothelial cells in the GelMA-nanosilicate colloidal network. Using this approach, it is possible to induce cell patterning, enhance vascularization, and direct cellular function. The proposed biphasic bioink holds significant potential for numerous emerging biomedical applications, including tissue engineering and disease modeling.

Expression of Concern: Investigation of the Mechanical Stability of Polyethylene Glycol Hydrogel Reinforced with Cellulose Nanofibrils for Wound Healing: Molecular Dynamics Simulation

Expression of Concern: Investigation of the Mechanical Stability of Polyethylene Glycol Hydrogel Reinforced with Cellulose Nanofibrils for Wound Healing: Molecular Dynamics Simulation

In Vitro Antibacterial and Anti-Inflammatory Properties of Imidazolium Poly(ionic liquids) Microspheres Loaded in GelMA-PEG Hydrogels.

Repairing damaged tissue caused by bacterial infection poses a significant challenge. Traditional antibacterial hydrogels typically incorporate various components such as metal antimicrobials, inorganic antimicrobials, organic antimicrobials, and more. However, drawbacks such as the emergence of multi-drug resistance to antibiotics, the low antibacterial efficacy of natural agents, and the potential cytotoxicity associated with metal antibacterial nanoparticles in hydrogels hindered their broader clinical application. In this study, we successfully developed imidazolium poly(ionic liquids) (PILs) polymer microspheres (APMs) through emulsion polymerization. These APMs exhibited notable antibacterial effectiveness and demonstrated minimal cell toxicity. Subsequently, we integrated the APMs into a gelatin methacryloyl (GelMA)-polyethylene glycol (PEG) hydrogel. This composite hydrogel not only showcased strong antibacterial and anti-inflammatory properties but also facilitated the migration of human skin fibroblasts (HSF) and human umbilical vein endothelial cells (HUVECs) and promoted osteogenic differentiation in vitro.

Light-sensitive PEG hydrogel with antibacterial performance for pacemaker pocket infection prevention

Prevention of cardiovascular implantable electronic devices (CIED) infection is crucial for successful outcomes. In this study, we report an adhesive and antibacterial hydrogel coating for CIED infection treatment, by immobilizing polyethylene glycol (PEG) and 2′-O-hydroxypropyl trimethyl ammonium chloride chitosan (HAC) on Ti surface. Initial alkali and APTES treatment caused the formation of –NH2 to enhance the adhesion of the hydrogel coating to Ti implants, followed by immobilizing a photo-cross-linkable PEG/2′-O-HTACCS hydrogel on Ti/OH/NH2 surface. Surface characterization of Ti/OH/NH2 sample and adhesion testing of hydrogel on Ti/OH/NH2 surface confirm successful immobilization of hydrogel onto the Ti/OH/NH2 surface. In vitro and in vivo antimicrobial results exhibited that the photo-cross-linkable PEG/HAC composite hydrogel has excellent antimicrobial capabilities against both Grampositive (S. aureus and S. epidermidis) and Gram-negative (P. aeruginosa and E. coli) bacteria. The outcome of this study demonstrates the photo-cross linked PEG/HAC coating hydrogels can be easily formed on the Ti implants, and has great potential in preventing CIED pocket infection.

PEG hydrogel sealant versus fibrin glue in posterior fossa surgery: an economic comparison across five European countries.

Aim: Posterior cranial fossa (PCF) surgery is associated with complications, including cerebrospinal fluid (CSF) leakage. Dural sealants such as polyethylene glycol (PEG)-based hydrogels and fibrin glue can prevent CSF leaks, with evidence suggesting PEG hydrogels may outperform fibrin glue. However, the budget impact of using PEG hydrogels in PCF surgeries in Europe is unclear. Materials & methods: A decision tree was developed based on a previous US model, to assess the budget impact of switching from fibrin glue to PEG hydrogel in PCF surgery across five European countries. Input costs were derived from published sources for the financial year 2022/2023. Health outcomes, including CSF leaks, were considered. Results: The model predicted that using PEG hydrogel instead of fibrin glue in PCF surgery can lead to cost savings in five European countries. Cost savings per patient ranged from EUR 419 to EUR 1279, depending on the country. Sensitivity analysis showed that the incidence of CSF leaks and pseudomeningoceles had a substantial impact on the model's results. Conclusion: PEG hydrogels may be a cost-effective alternative to fibrin glue in PCF surgery. The model predicted that cost savings would be mainly driven by a reduction in the incidence of postoperative CSF leaks, resulting in reduced reliance on lumbar drains, reparative surgery and shortened hospital stays.

Enhanced Hemostatic and Procoagulant Efficacy of PEG/ZnO Hydrogels: A Novel Approach in Traumatic Hemorrhage Management.

Managing severe bleeding, particularly in soft tissues and visceral injuries, remains a significant challenge in trauma and surgical care. Traditional hemostatic methods often fall short in wet and dynamic environments. This study addresses the critical issue of severe bleeding in soft tissues, proposing an innovative solution using a polyethylene glycol (PEG)-based hydrogel combined with zinc oxide (ZnO). The developed hydrogel forms a dual-network structure through amide bonds and metal ion chelation, resulting in enhanced mechanical properties and adhesion strength. The hydrogel, exhibiting excellent biocompatibility, is designed to release zinc ions, promoting coagulation and accelerating hemostasis. Comprehensive characterization, including gelation time, rheological properties, microstructure analysis, and swelling behavior, demonstrates the superior performance of the PEG/ZnO hydrogel compared to traditional PEG hydrogels. Mechanical tests confirm increased compression strength and adhesive properties, which are crucial for withstanding tissue dynamics. In vitro assessments reveal excellent biocompatibility and enhanced procoagulant ability attributed to ZnO. Moreover, in vivo experiments using rat liver and tail bleeding models demonstrate the remarkable hemostatic performance of the PEG/ZnO hydrogel, showcasing its potential for acute bleeding treatment in both visceral and peripheral scenarios.

Human induced pluripotent stem cell-derived planar neural organoids assembled on synthetic hydrogels

The tailorable properties of synthetic polyethylene glycol (PEG) hydrogels make them an attractive substrate for human organoid assembly. Here, we formed human neural organoids from iPSC-derived progenitor cells in two distinct formats: (i) cells seeded on a Matrigel surface; and (ii) cells seeded on a synthetic PEG hydrogel surface. Tissue assembly on synthetic PEG hydrogels resulted in three dimensional (3D) planar neural organoids with greater neuronal diversity, greater expression of neurovascular and neuroinflammatory genes, and reduced variability when compared with tissues assembled upon Matrigel. Further, our 3D human tissue assembly approach occurred in an open cell culture format and created a tissue that was sufficiently translucent to allow for continuous imaging. Planar neural organoids formed on PEG hydrogels also showed higher expression of neural, vascular, and neuroinflammatory genes when compared to traditional brain organoids grown in Matrigel suspensions. Further, planar neural organoids contained functional microglia that responded to pro-inflammatory stimuli, and were responsive to anti-inflammatory drugs. These results demonstrate that the PEG hydrogel neural organoids can be used as a physiologically relevant in vitro model of neuro-inflammation.

Drug-Releasing Tannic Acid-Mediated Adhesive PEG Hydrogel for Porous Titanium Implants.

Porous titanium implants are commonly utilized for orthopedic surgery because they can mimic the mechanical properties and porous structure of human bone. However, the bioinertness of titanium (Ti) has been reported to obstruct biointegration processes, resulting in slower bone repair. Here, we propose a localized drug delivery system on Ti surfaces using adhesive hydrogel to enhance biological-Ti interactions. The hydrogel was fabricated from polyethylene glycol (PEG), which was cross-linked by the complex of tannic acid (TA) and 1,4-phenylenediboronic acid (PDBA) and stabilized by bovine serum albumin (BSA). The hydrogel was formed and attached to a Ti plate to investigate stability, biodegradability, controlled drug release, and biocompatibility. The stability and biodegradability of the hydrogel could be tuned by adjusting the concentrations of BSA and TA. The hydrogel lasted and remained adhered to the Ti surface after being submerged in PBS for at least 15 days. The controlled release of strontium ranelate (SrRan) and the release mechanism depended on the amount of TA since it was found to govern the hydrogel integrity and pore size. Additionally, in vitro biocompatibility was validated using L929 fibroblast and MC3T3-E1 osteoblast cells that showed greater than 70% viability. The adhesive hydrogel was further studied by injecting it into a 3D-printed Ti-scaffold that contained a porous structure mimicking natural human bone. The hydrogel completely filled and adhered to the inner porous structure of the scaffold. The biodegradation and drug release of the hydrogel in the scaffold occurred at a slower rate, suggesting sustainable drug release that is suitable for bone cell regeneration. The overall results in biodegradability, controlled drug release, and biocompatibility demonstrate the great potential of the drug-releasing TA-mediated adhesive PEG hydrogel as a Ti-enhancing biomaterial that supports osseointegration.