Poly Ethylene Glycol Hydrogels Research Articles

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, we introduce a novel solution: a biphasic, granular colloidal bioink designed to optimize cell viability and printing fidelity. The biphasic ink consists of cell-laden polyethylene glycol (PEG) hydrogel microparticles embedded in a continuous gelatin methacryloyl (GelMA)-nanosilicate colloidal network. Here, we demonstrate that this biphasic bioink offers outstanding rheological properties, print fidelity, and structural stability. Furthermore, we demonstrate its utility for engineering complex tissues with multiple cell types and heterogeneous microenvironments, which we demonstrate 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. This article is protected by copyright. All rights reserved.

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.

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

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 head of 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.

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.

Aspects of the alternative host response to methacrylic acid containing biomaterials.

Methacrylic acid (MAA)-based biomaterials promote a vascularized host response without the addition of exogenous factors such as cells or growth factors. We presume that materials containing MAA favor an alternative foreign body response, rather than the conventional fibrotic response. Here, we characterize selected aspects of the response to two different forms of MAA-a coating, which can be used to prevascularize the subcutaneous tissue for subsequent therapeutic cell delivery or an injectable hydrogel, which can be used to vascularize and deliver cells simultaneously. We show that the MAA-coating quickly vascularized the subcutaneous space compared to an uncoated silicone tube, and after 14 days of prevascularization, the tissue surrounding the MAA-coated tube presented fewer immune cells than the uncoated control. We also compared the host response to a MAA-PEG (polyethylene glycol) hydrogel at day 1, with pancreatic islets in immune-compromised SCID/bg mice and immune-competent Balb/c mice. The Balb/c mouse presented a more inflammatory response with increased IFN-γ production as compared to the SCID/bg. Together with previously published data, this work contributes to a further understanding of tissue responses to a biomaterial in different forms as used for cell delivery.

Soft and Conductive Polyethylene Glycol Hydrogel Electrodes for Electrocardiogram Monitoring.

The measurement of biosignals in the clinical and healthcare fields is fundamental; however, conventional electrodes pose challenges such as incomplete skin contact and skin-related issues, hindering accurate biosignal measurement. To address these challenges, conductive hydrogels, which are valuable owing to their biocompatibility and flexibility, have been widely developed and explored for electrode applications. In this study, we fabricated a conductive hydrogel by mixing polyethylene glycol diacrylate (PEGDA) with poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) polymers dissolved in deionized water, followed by light-triggered crosslinking. Notably, this study pioneered the use of a PEGDA-PEDOT:PSS hydrogel for electrocardiogram (ECG) monitoring- a type of biosignal. The resulting PEGDA-PEDOT:PSS hydrogel demonstrated remarkable conductivity while closely approximating the modulus of skin elasticity. Additionally, it demonstrated biocompatibility and a high signal-to-noise ratio in the waveforms. This study confirmed the exceptional suitability of the PEGDA-PEDOT:PSS hydrogel for accurate biosignal measurements with potential applications in various wearable devices designed for biosignal monitoring.

Time-gated luminescent probes for lysosomal singlet oxygen: Synthesis, characterizations and bioimaging applications

BackgroudSingle oxygen (1O2), the molecular oxygen at its excited state, plays a crucial role in the photodynamic therapy (PDT) of some diseases owing to its strong oxidizing property to destroy malignant cells. Although the fluorescent probe technique has proven its powerful application abilities for detection of 1O2 in biological systems, most of the reported fluorescent probes suffered from the interference of background autofluorescence of biological samples. It is clear that the real-time and in situ, background-free fluorescent detection of 1O2 generated in live cells, especially in some organelles, is of great significance for understanding the action mechanism of PDT drugs. ResultsBy introducing a lysosome-anchoring motif, a morpholine moiety, into a 1O2-specifically-reactive terpyridine polyacid ligand, [4’-(9-anthryl)-2,2’:6′,2″-terpyridine-6,6″-diyl] bis(methylenenitrilo) tetrakis (acetic acid) (ATTA), and chelating with lanthanide ions (Eu3+ or Tb3+), two lanthanide complex-based “turn-on” luminescent probes that can be used for the background-free time-gated luminescent (TGL) detection of lysosomal 1O2, Lyso-ATTA-Eu3+ and Lyso-ATTA-Tb3+, have been developed. The probes exhibit fast luminescence responses (within 2.5 min) towards 1O2 with high selectivity and sensitivity (<0.75 μM) in a wide pH range (4–11). And the excellent lysosome-localization performance of the probes allowed them to be used for the monitoring of endogenous 1O2 in lysosomes, which enabled the variability of lysosomal-1O2 concentrations induced by different photosensitizers to be successfully discriminated. Furthermore, by doping Lyso-ATTA-Eu3+ into the polyethylene glycol (PEG) hydrogel, the smart luminescent sensor film, PEG-Lyso-ATTA-Eu3+, was prepared, and successfully used for the detection of the on-site 1O2 production during the PDT process of psoriatic disease in model mice. SignificantTwo lysosome-targetable background-free TGL probes for 1O2 were firstly reported. The developed smart luminescent sensor film could be a powerful tool for the clinical monitoring of PDT on skin diseases without using sophisticated and expensive instruments.

Polyethylene glycol hydrogel coatings for protection of electroactive bacteria against chemical shocks

Loss of bioelectrochemical activity in low resource environments or from chemical toxin exposure is a significant limitation in microbial electrochemical cells (MxCs), necessitating the development of materials that can stabilize and protect electroactive biofilms. Here, polyethylene glycol (PEG) hydrogels were designed as protective coatings over anodic biofilms, and the effect of the hydrogel coatings on biofilm viability under oligotrophic conditions and ammonia-N (NH4+-N) shocks was investigated. Hydrogel deposition occurred through polymerization of PEG divinyl sulfone and PEG tetrathiol precursor molecules, generating crosslinked PEG coatings with long-term hydrolytic stability between pH values of 3 and 10. Simultaneous monitoring of coated and uncoated electrodes co-located within the same MxC anode chamber confirmed that the hydrogel did not compromise biofilm viability, while the coated anode sustained nearly a 4 × higher current density (0.44 A/m2) compared to the uncoated anode (0.12 A/m2) under oligotrophic conditions. Chemical interactions between NH4+-N and PEG hydrogels revealed that the hydrogels provided a diffusive barrier to NH4+-N transport. This enabled PEG-coated biofilms to generate higher current densities during NH4+-N shocks and faster recovery afterwards. These results indicate that PEG-based coatings can expand the non-ideal chemical environments that electroactive biofilms can reliably operate in.

Increasing rectum–prostate distance using a hydrogel spacer to reduce radiation exposure during proton beam therapy for prostate cancer

SpaceOAR, a polyethylene-glycol hydrogel, reduces rectal radiation exposure during radiation therapy for prostate cancer. Previously, our group reported the modified technique of hydrogel insertion, which achieves greater separated distance at prostate-apex. This study aimed to investigate the impact of separated distance at prostate-apex and our modifier technique, on radiation exposure reduction during proton beam therapy (PBT). We included 330 patients undergoing PBT with the relative biological effectiveness (RBE) of 63 Gray (Gy) for localized prostate cancer, and categorized them into groups 0 (no spacer, n = 141), 1 (separated distance of spacer at the prostate-apex level < 7.5 mm, n = 81), and 2 (distance ≥ 7.5 mm, n = 108). The rectal volumes to receive 30–60 Gy (RBE), was estimated and described as Rectal V30–60 (ml) in 10 Gy increments. The Rectal V30–60 (ml) was significantly lower in group 2 than in group 1, and in group 1 than in group 0. After propensity score matching, the multivariate logistic regression analysis revealed that the most significant factor to reduce radiation exposure was our modified technique of hydrogel insertion. Therefore, using a hydrogel spacer to expand the prostate–rectum distance not only at prostate-mid to prostate-base level but also at the prostate-apex level can reduce the radiation exposure in PBT for prostate cancer.

A robust theoretical approach to analyze the diffusion of natural and synthetic wound antimicrobials through polyethylene glycol hydrogel using obstruction theory

A robust theoretical approach to analyze the diffusion of natural and synthetic wound antimicrobials through polyethylene glycol hydrogel using obstruction theory

Biological Effective Dose (BED) in Evaluation of Rectal Dose in Prostate Cancer Patients with Hydrogel Spacer Who Underwent an EBRT with Different Fractionation Schemes

To evaluate rectal dose sparing in prostate cancer patients with hydrogel spacer who underwent an external beam radiotherapy (EBRT) with different fractionation schemes. In a previous study, we have reported that rectal sparing was achieved in prostate cancer patients with hydrogel spacer who underwent a combination therapy of EBRT and LDR brachytherapy (Zhang H, et al. J Appl Clin Med Phys, 2022). In this study, we focused on evaluation of spacer-related rectal sparing in patients who underwent an EBRT with conventional fractionation (81 Gy in 45 fractions), hypofractionation (70 Gy in 28 fractions), or stereotactic body radiotherapy (SBRT) for 40 Gy or 42.5 Gy in 5 fractions. In 172 patients, 119 patients were applied with injection of polyethylene-glycol hydrogel and others without the injection as control. In VMAT plans, doses to rectal wall were examined and converted to BED according to AAPM TG-137 (α/β ratio = 4 Gy). On average, an interspace of 1cm between prostate and rectum was achieved by spacer insertion. Rectal wall was defined as 0.4cm thickness inside the outer contour of rectum, and the volume ranged from 4.5 cm3 to 21.3cm3 for patients with spacer and from 8.2cm3 to 35.1cm3 for those with no spacer. In conventional scheme, an average rectal BED was 120.0 Gy, 116.9 Gy, 114.0 Gy, 108.6 Gy, 87.6 Gy and 55.6 Gy to the volume of 0.1, 0.5, 1, 2, 5 and 10cm3, respectively, and BEDmean was 55.3 Gy in patients with no spacer. The BED decreased to 105.1 Gy, 96.3 Gy, 86.1 Gy, 75.4 Gy, 51.7 Gy and 26.9 Gy to the volume of 0.1, 0.5, 1, 2, 5 and 10cm3, respectively (p < 0.01), and BEDmean was 46.0 Gy in patients with spacer. In hypofractionation, rectal BED was in average of 115.8 Gy, 112.3 Gy, 109.8 Gy, 103 Gy, 81.6 and 52.8 Gy to the volume of 0.1, 0.5, 1, 2, 5 and 10cm3, respectively, and BEDmean was 48.6 Gy in patients with no spacer. Patients with spacer had significantly decreases of rectal BED, an average of 103 Gy, 91.7 Gy, 84.1 Gy, 72.8 Gy, 48.8 Gy and 26.0 Gy to the volume of 0.1, 0.5, 1, 2, 5 and 10cm3, respectively (p < 0.01), BEDmean was 42.4 Gy. In SBRT, average rectal BED in patients with spacer decreased to 93.6 Gy, 78.4 Gy, 69 Gy, 57.5 Gy, 38.5 Gy and 21.5 Gy, in comparison of 124.1 Gy, 117,4 Gy, 110.9 Gy, 97.3 Gy, 59.7 Gy and 32.3 Gy to the volume of 0.1, 0.5, 1, 2, 5 and 10cm3 in those without spacer, respectively (p <0.01). BEDmean decreased to 32.0 Gy in patient with spacer, compared with 43.2 Gy in those with no spacer. Insertion of hydrogel spacer significantly improved rectal dose sparing, about 11.1% to 50.8% in conventional scheme, 12.4% to 51.6% in hypofractionation scheme, and 24.6% to 40.9% in SBRT patients. Furthermore, relatively more dose sparing on rectum was seen on the volume from 0.1cm3 to 2cm3 in SBRT patients.

Tumor Spheroid Fabrication and Encapsulation in Polyethylene Glycol Hydrogels for Studying Spheroid-Matrix Interactions.

Three-dimensional (3D) encapsulation of spheroids is crucial to adequately replicate the tumor microenvironment for optimal cell growth. Here, we designed an in vitro 3D glioblastoma model for spheroid encapsulation to mimic the tumor extracellular microenvironment. First, we formed square pyramidal microwell molds using polydimethylsiloxane. These microwell molds were then used to fabricate tumor spheroids with tightly controlled sizes from 50-500 μm. Once spheroids were formed, they were harvested and encapsulated in polyethylene glycol (PEG)-based hydrogels. PEG hydrogels are a versatile platform for spheroid encapsulation, as hydrogel properties such as stiffness, degradability, and cell adhesiveness can be tuned independently. Here, we used a representative soft (~8 kPa) hydrogel to encapsulate glioblastoma spheroids. Finally, a method to stain and image spheroids was developed to obtain high-quality images via confocal microscopy. Due to the dense spheroid core and relatively sparse periphery, imaging can be difficult, but using a clearing solution and confocal optical sectioning helps alleviate these imaging difficulties. In summary, we show a method to fabricate uniform spheroids, encapsulate them in PEG hydrogels and perform confocal microscopy on the encapsulated spheroids to study spheroid growth and various cell-matrix interactions.

Cytocompatibility Evaluation of PEG-Methylsulfone Hydrogels.

Methylsulfone derivatized poly(ethylene) glycol (PEG) macromers can be biofunctionalized with thiolated ligands and cross-linked with thiol-based cross-linkers to obtain bioactive PEG hydrogels for in situ cell encapsulation. Methylsulfonyl-thiol (MS-SH) reactions present several advantages for this purpose when compared to other thiol-based cross-linking systems. They proceed with adequate and tunable kinetics for encapsulation, they reach a high conversion degree with good selectivity, and they generate stable reaction products. Our previous work demonstrated the cytocompatibility of cross-linked PEG-MS/thiol hydrogels in contact with fibroblasts. However, the cytocompatibility of the in situ MS-SH cross-linking reaction itself, which generates methylsulfinic acid as byproduct at the cross-linked site, remains to be evaluated. These studies are necessary to evaluate the potential of these systems for in vivo applications. Here we perform an extensive cytocompatibility study of PEG hydrogels during in situ cross-linking by the methylsulfonyl-thiol reaction. We compare these results with maleimide-thiol cross-linked PEGs which are well established for cell culture and in vivo experiments and do not involve the release of a byproduct. We show that fibroblasts and endothelial cells remain viable after in situ polymerization of methylsulfonyl-thiol gels on the top of the cell layers. Cell viability seems better than after in situ cross-linking hydrogels with maleimide-thiol chemistry. The endothelial cell proinflammatory phenotype is low and similar to the one obtained by the maleimide-thiol reaction. Finally, no activation of monocytes is observed. All in all, these results demonstrate that the methylsulfonyl-thiol chemistry is cytocompatible and does not trigger high pro-inflammatory responses in endothelial cells and monocytes. These results make methylsulfonyl-thiol chemistries eligible for in vivo testing and eventually clinical application in the future.

Technology platform for facile handling of 3D hydrogel cell culture scaffolds

Hydrogels are used extensively as cell-culture scaffolds for both 2D and 3D cell cultures due to their biocompatibility and the ease in which their mechanical and biological properties can be tailored to mimic natural tissue. The challenge when working with hydrogel-based scaffolds is in their handling, as hydrogels that mimic e.g. brain tissue, are both fragile and brittle when prepared as thin (sub-mm) membranes. Here, we describe a method for facile handling of thin hydrogel cell culture scaffolds by molding them onto a polycaprolactone (PCL) mesh support attached to a commonly used Transwell set-up in which the original membrane has been removed. In addition to demonstrating the assembly of this set-up, we also show some applications for this type of biological membrane. A polyethylene glycol (PEG)-gelatin hydrogel supports cell adhesion, and the structures can be used for biological barrier models comprising either one or multiple hydrogel layers. Here, we demonstrate the formation of a tight layer of an epithelial cell model comprising MDCK cells cultured over 9 days by following the build-up of the transepithelial electrical resistances. Second, by integrating a pure PEG hydrogel into the PCL mesh, significant swelling is induced, which leads to the formation of a non-adherent biological scaffold with a large curvature that is useful for spheroid formation. In conclusion, we demonstrate the development of a handling platform for hydrogel cell culture scaffolds for easy integration with conventional measurement techniques and miniaturized organs-on-chip systems.

Dynamics of underwater microparticle adhesion to soft hydrated surfaces: Modeling and analysis by time-dependent AFM force spectroscopy

HypothesisUnderstanding the attachment and detachment of microparticles and living cells to surfaces is crucial for developing antifouling strategies. Hydrogel coatings have shown promise in reducing fouling and particle adhesion due to their softness and high water content, yet the mechanisms involved are dynamic and complex, and relevant parameters are not easily accessible. AFM-based force spectroscopy (FS) experiments with colloidal probe particles is a direct way of evaluating adhesive and mechanical relaxational dynamics, yet their interpretation and modeling has been challenging. The present study proposes and examines several dynamic models, suitable for quantitative analysis of FS results with model probe particle on hydrogels surfaces. ExperimentsFS were performed using polyethylene glycol (PEG) hydrogels and polystyrene microspheres including particle attachement to the hydrogel surface (loading), holding the particle on the surface with a constant force for variable times (dwell) and pulling the particle away from the surface (unloading) FindingsIt was found that a viscoelastic extension of the classical JKR model with energy of adhesion unevenly distributed over the contact area and vanishing at its circumferences accurately described all FS experiments and yielded physically consistent viscoelastic and adhesive dynamic parameters, steadily changing with dwell time and applied force. The observed time evolution and force dependence were rationalized as combination of osmotic and osmo-mechnical relaxation in the contact region.