Poly(ethylene Glycol) Diacrylate Molecular Weight Research Articles

In Vitro Investigation of Vocal Fold Cellular Response to Variations in Hydrogel Porosity and Elasticity.

Tissue regeneration is intricately influenced by the dynamic interplay between the physical attributes of tissue engineering scaffolds and the resulting biological responses. A tunable microporous hydrogel system was engineered using gelatin methacryloyl (GelMA) and polyethylene glycol diacrylate (PEGDA), with polyethylene glycol (PEG) serving as a porogen. Through systematic variation of PEGDA molecular weights, hydrogels with varying mechanical and architectural properties were obtained. The objective of the present study was to elucidate the impact of substrate mechanics and architecture on the immunological and reparative activities of vocal fold tissues. Mechanical characterization of the hydrogels was performed using tensile strength measurements and rheometry. Their morphological properties were investigated using scanning electron microscopy (SEM) and confocal microscopy. A series of biological assays were conducted. Cellular morphology, differentiation, and collagen synthesis of human vocal fold fibroblasts (hVFFs) were evaluated using immunostaining. Fibroblast proliferation was studied using the WST-1 assay, and cell migration was investigated via the Boyden chamber assay. Macrophage polarization and secretions were also examined using immunostaining and ELISA. The results revealed that increasing the molecular weight of PEGDA from 700 Da to 10,000 Da resulted in decreased hydrogel stiffness, from 62.6 to 8.8 kPa, and increased pore dimensions from approximately 64.9 to 137.4 μm. Biological evaluations revealed that hydrogels with a higher stiffness promoted fibroblast proliferation and spreading, albeit with an increased propensity for fibrosis, as indicated by a surge in myofibroblast differentiation and collagen synthesis. In contrast, hydrogels with greater molecular weights had a softer matrix with expanded pores, enhancing cellular migration and promoting an M2 macrophage phenotype conducive to tissue healing. The findings show that the hydrogels formulated with a PEGDA molecular weight of 6000 Da are best among the hydrogels considered for vocal fold repair. The microporous hydrogels could be tuned to serve in other tissue engineering applications.

Digital Light 3D Printing of PEDOT-Based Photopolymerizable Inks for Biosensing.

3D conductive materials such as polymers and hydrogels that interface between biology and electronics are actively being researched for the fabrication of bioelectronic devices. In this work, short-time (5 s) photopolymerizable conductive inks based on poly(3,4-ethylenedioxythiophene) (PEDOT):polystyrene sulfonate (PSS) dispersed in an aqueous matrix formed by a vinyl resin, poly(ethylene glycol) diacrylate (PEGDA) with different molecular weights (Mn = 250, 575, and 700 Da), ethylene glycol (EG), and a photoinitiator have been optimized. These inks can be processed by Digital Light 3D Printing (DLP) leading to flexible and shape-defined conductive hydrogels and dry conductive PEDOTs, whose printability resolution increases with PEGDA molecular weight. Besides, the printed conductive PEDOT-based hydrogels are able to swell in water, exhibiting soft mechanical properties (Young’s modulus of ∼3 MPa) similar to those of skin tissues and good conductivity values (10–2 S cm–1) for biosensing. Finally, the printed conductive hydrogels were tested as bioelectrodes for human electrocardiography (ECG) and electromyography (EMG) recordings, showing a long-term activity, up to 2 weeks, and enhanced detection signals compared to commercial Ag/AgCl medical electrodes for health monitoring.

Development of a two-part biomaterial adhesive strategy for annulus fibrosus repair and ex vivo evaluation of implant herniation risk

Intervertebral disc (IVD) herniation causes pain and disability, but current discectomy procedures alleviate pain without repairing annulus fibrosus (AF) defects. Tissue engineering strategies seal AF defects by utilizing hydrogel systems to prevent recurrent herniation, however current biomaterials are limited by poor adhesion to wetted tissue surfaces or low failure strength resulting in considerable risk of implant herniation upon spinal loading. Here, we developed a two-part repair strategy comprising a dual-modified (oxidized and methacrylated) glycosaminoglycan that can chemically adsorb an injectable interpenetrating network hydrogel composed of fibronectin-conjugated fibrin and poly (ethylene glycol) diacrylate (PEGDA) to covalently bond the hydrogel to AF tissue. We show that dual-modified hyaluronic acid imparts greater adhesion to AF tissue than dual-modified chondroitin sulfate, where the degree of oxidation is more strongly correlated with adhesion strength than methacrylation. We apply this strategy to an ex vivo bovine model of discectomy and demonstrate that PEGDA molecular weight tunes hydrogel mechanical properties and affects herniation risk, where IVDs repaired with low-modulus hydrogels composed of 20kDa PEGDA failed at levels at or exceeding discectomy, the clinical standard of care. This strategy bonds injectable hydrogels to IVD extracellular matrix proteins, is optimized to seal AF defects, and shows promise for IVD repair.

Integrative control of mechanical and degradation properties of in situ crosslinkable polyamine-based hydrogels for dual-mode drug release kinetics

Michael addition is extensively utilized to fabricate hydrogels for biomedical applications, due their ability to undergo crosslinking reaction under physiological conditions without the need of a catalyst. Herein, mechanical properties and degradation behavior of in situ crosslinkable poly (ethylene glycol) diacrylate (PEGDA)-polyethyleneimine (PEI) hydrogels are explored. PEGDA and PEI, having acrylate and amine groups respectively, undergo crosslinking reaction via Michael addition to form hydrogels. The mechanical properties are controlled in a wide range by varying their concentrations and the molecular weight of PEGDA. In addition, the hydrogels are all shown to undergo degradation due to the expedited hydrolysis of ester linkages by the presence of unreacted amine groups on PEI. With this interesting combination of tunable mechanical properties and degradation, the PEGDA-PEI hydrogel system display a dual-mode drug release kinetics in which the drug release was governed by swelling-controlled and degradation-controlled mechanisms in sequence, which demonstrates the potential for drug delivery applications.

Free radical polymerization of polyvinyl butyral/polyethylene glycol diacrylate copolymer for removing organic dyes from waste water

Copolymers of polyvinyl butyral (PVB)/polyethylene glycol diacrylate (PEGDA) were prepared by free radical polymerization using gamma irradiation. The physical properties such as gelation, swelling and the thermal behavior of the prepared PVB/PEGDA copolymer were investigated as a function of molecular weight of PEGDA. The thermal behavior of blank PVB (PVB/PEGDA)-575 and (PVB/PEGDA)-750 copolymers as a function of absorbed dose up to 100 kGy was determined using thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). The thermal stability of the prepared copolymers was improved by gamma irradiation, PEGDA and the increasing of PEGDA molecular weight. Two textile dyes, Diamine Fast Scarlet GG and Direct Pink 3B, were used as model anionic dyes. The adsorption of PVB/PEGDA hydrogels of different molecular weights was investigated towards the two anionic dyes by the batch equilibrium method. The adsorption capacity of the copolymers was evaluated as a function of initial dye concentration, different molecular weight, and time. The equilibrium data obtained in batch experiments were correlated to Langmuir and Freundlich isotherm equations. Results showed that the adsorption of Direct Pink 3B fitted well to the Langmuir model, while the adsorption pattern of Diamine Fast Scarlet GG followed the Freundlich isotherm, which suggests heterogeneity of the adsorption sites on the copolymer. Thermodynamic data revealed spontaneous exothermic processes and was a physisorption reaction. Our results demonstrate that the PVB/PEGDA copolymer is very promising for removing organic dyes from waste water.

Highly conductive solvent-free polymer electrolyte membrane for lithium-ion batteries: Effect of prepolymer molecular weight

The present article demonstrates the effects of molecular weight of network precursor on properties of solid-state polymer electrolyte membrane (PEM) comprised of poly (ethylene glycol) diacrylate (PEGDA) prepolymer, succinonitrile (SCN) plasticizer, and lithium bis(trifluoromethane sulphonyl) imide (LiTFSI) salt using two different PEGDA molecular weights. To provide guidance for crosslinking reaction, ternary phase diagrams of the PEM precursor mixtures were established. Upon photopolymerization within the wide isotropic region, completely amorphous membranes were obtained in several compositions. The PEM having a higher PEGDA molecular weight (i.e., 6000g/mol) revealed both improved impact strength with an elongation at break of ~80 % and higher ambient temperature ionic conductivity (~1.4×10−3Scm−1) relative to the low molecular weight counterpart (i.e., 700g/mol). Both PEMs exhibited excellent electrochemical (4.8V/Li/Li+) and thermal (140°C) stabilities. Specific discharge capacities of the PEM containing half-cells using LiFePO4 or Li4Ti5O12 electrodes against lithium electrode reached the level of ~140mAhg−1 at 0.2°C, indicating potential applications in all solid-state lithium-ion batteries.

In situ-preparation and characterization of silver-HEMA/PEGDA hydrogel matrix nanocomposites: Silver inclusion studies into hydrogel matrix

Poly(ethylene glycol) diacrylate (PEGDA) of different molecular weights (Mn=575 and 700) was used as crosslinking agent for the photopolymerization of 2-hydroxyethyl methacrylate (HEMA) in order to obtain HEMA/PEGDA-based hydrogels. Composites were synthesized in situ employing a new methodology that implies the addition of different quantities of silver nitrate aqueous solution to the monomer mixture with the finality to obtain hydrogels with different silver nanoparticles’ spatial density and distribution. Samples were characterized by thermal, optical, spectroscopic and structural/morphological methods. Thermal studies showed that the increase of PEGDA molecular weight and the AgNO3 concentration in the reaction mixture enhance the glass transition temperature and the thermal stability of the composites. This behavior could be related to the silver coordination with the polymer network. Infrared spectroscopy with Fourier transform and Raman analyses were realized in order to corroborate the sample chemical structure by the identification of specific functional groups. Surface hydrogel morphology was visualized with scanning electron microscopy analysis, detecting a homogeneous micro-porous surface for the samples obtained from high molecular weight PEGDA. Presence of silver nanoparticles was established by X-ray fluorescence spectroscopy and UV/Vis methods. In this last case, the characteristic silver nanoparticle plasmon was observed. Using Transmission Electron Microscopy it was possible to visualize a homogeneous spatial distribution of spherical silver nanoparticles with very narrow diameter distribution that rounds about 14–21±5nm. In general, the silver nanoparticle presence in the compounds enhances considerably their thermal/morphological characteristics.

Tuning mechanical performance of poly(ethylene glycol) and agarose interpenetrating network hydrogels for cartilage tissue engineering

Hydrogels are attractive for tissue engineering applications due to their incredible versatility, but they can be limited in cartilage tissue engineering applications due to inadequate mechanical performance. In an effort to address this limitation, our team previously reported the drastic improvement in the mechanical performance of interpenetrating networks (IPNs) of poly(ethylene glycol) diacrylate (PEG-DA) and agarose relative to pure PEG-DA and agarose networks. The goal of the current study was specifically to determine the relative importance of PEG-DA concentration, agarose concentration, and PEG-DA molecular weight in controlling mechanical performance, swelling characteristics, and network parameters. IPNs consistently had compressive and shear moduli greater than the additive sum of either single network when compared to pure PEG-DA gels with a similar PEG-DA content. IPNs withstood a maximum stress of up to 4.0 MPa in unconfined compression, with increased PEG-DA molecular weight being the greatest contributing factor to improved failure properties. However, aside from failure properties, PEG-DA concentration was the most influential factor for the large majority of properties. Increasing the agarose and PEG-DA concentrations as well as the PEG-DA molecular weight of agarose/PEG-DA IPNs and pure PEG-DA gels improved moduli and maximum stresses by as much as an order of magnitude or greater compared to pure PEG-DA gels in our previous studies. Although the viability of encapsulated chondrocytes was not significantly affected by IPN formulation, glycosaminoglycan (GAG) content was significantly influenced, with a 12-fold increase over a three-week period in gels with a lower PEG-DA concentration. These results suggest that mechanical performance of IPNs may be tuned with partial but not complete independence from biological performance of encapsulated cells.

Effects of Molecular Weight and Loading on Matrix Metalloproteinase-2 Mediated Release from Poly(Ethylene Glycol) Diacrylate Hydrogels

Herein, we report on continued efforts to understand an implantable poly(ethylene glycol) diacrylate (PEGDA) hydrogel drug delivery system that responds to extracellular enzymes, in particular matrix metalloproteinase-2 (MMP-2) to provide controlled drug delivery. By attaching peptide as pendant groups on the hydrogel backbone, drug release occurs at an accelerated rate in the presence of active protease. We investigated MMP-2 entry and optimized parameters of the drug delivery system. Mesh size for different PEGDA molecular weight macromers was measured with PEGDA 3,400 hydrogels having a mesh size smaller than the dimensions of MMP-2 and PEGDA 10,000 and PEGDA 20,000 hydrogels having mesh sizes larger than MMP-2. Purified MMP-2 increased release of peptide fragment compared to buffer at several loading concentrations. Cell-stimulated release was demonstrated using U-87 MG cells embedded in collagen. GM6001, an MMP inhibitor, diminished release and altered the identity of the released peptide fragment. The increase in ratio of release from PEGDA 10,000 and PEGDA 20,000 hydrogels compared to PEGDA 3,400 hydrogels suggests MMP-2 enters the hydrogel. PEGDA molecular weight of 10,000 and 15 % (w/V) were the optimal conditions for release and handling. The use of protease-triggered drug delivery has great advantage particularly with the control of protease penetration as a parameter for controlling rate of release.

Multi-material bio-fabrication of hydrogel cantilevers and actuators with stereolithography

Cell-based biohybrid actuators are integrated systems that use biological components including proteins and cells to power material components by converting chemical energy to mechanical energy. The latest progress in cell-based biohybrid actuators has been limited to rigid materials, such as silicon and PDMS, ranging in elastic moduli on the order of mega (10(6)) to giga (10(9)) Pascals. Recent reports in the literature have established a correlation between substrate rigidity and its influence on the contractile behavior of cardiomyocytes (A. J. Engler, C. Carag-Krieger, C. P. Johnson, M. Raab, H. Y. Tang and D. W. Speicher, et al., J. Cell Sci., 2008, 121(Pt 22), 3794-3802, P. Bajaj, X. Tang, T. A. Saif and R. Bashir, J. Biomed. Mater. Res., Part A, 2010, 95(4), 1261-1269). This study explores the fabrication of a more compliant cantilever, similar to that of the native myocardium, with elasticity on the order of kilo (10(3)) Pascals. 3D stereolithographic technology, a layer-by-layer UV polymerizable rapid prototyping system, was used to rapidly fabricate multi-material cantilevers composed of poly(ethylene glycol) diacrylate (PEGDA) and acrylic-PEG-collagen (PC) mixtures. The incorporation of acrylic-PEG-collagen into PEGDA-based materials enhanced cell adhesion, spreading, and organization without altering the ability to vary the elastic modulus through the molecular weight of PEGDA. Cardiomyocytes derived from neonatal rats were seeded on the cantilevers, and the resulting stresses and contractile forces were calculated using finite element simulations validated with classical beam equations. These cantilevers can be used as a mechanical sensor to measure the contractile forces of cardiomyocyte cell sheets, and as an early prototype for the design of optimal cell-based biohybrid actuators.

Preparation of poly(ethylene glycol) aligned porous cryogels using a unidirectional freezing technique

Poly(ethylene glycol) (PEG) cryogels with aligned porous structures were prepared by unidirectional freezing and subsequently cryopolymerization. The aqueous reaction precursor of poly(ethylene glycol) diacrylate (PEGDA) and the initiator was first unidirectionally frozen using liquid nitrogen or other cooling agents such as frozen ethyl alcohol and frozen acetic ether, followed by radical polymerization at subzero temperature. The morphology of the obtained cryogels was observed by scanning electron microscopy (SEM) and confocal laser scanning microscope (CLSM). The pore structure of the obtained cryogels was the replica of the unidirectional ice crystals formed during the unidirectional freezing. Microtubular pores aligned along the freezing direction were observed in both dry and swollen states. The obtained cryogels showed anisotropic compressive strength according to the pore directions. The effect of the PEGDA molecular weight and the freezing temperature on morphology of the orientation-structured cryogels were also studied. The pore diameter could be adjusted from 10 to 50 μm.

Synthesis, characterization and cytotoxicity of photo-crosslinked maleic chitosan–polyethylene glycol diacrylate hybrid hydrogels

Synthetic hydrogels are important biomaterials for many biomedical applications and hydrogels produced via photo-gelation have shown particular promise. In this paper, we describe a new family of biodegradable hybrid hydrogels fabricated in aqueous solution via long wavelength UV photo-crosslinking using maleic chitosan and polyethylene glycol diacrylate (PEGDA) as precursors. The maleic chitosan precursor was prepared by a simple one-step chemical modification of chitosan, with high yields, and characterized by Fourier transform infrared spectroscopy, (1)H NMR and (13)C NMR. Maleic chitosan and PEGDA precursors at a wide range of weight feed ratios were mixed in aqueous solution and directly photo-crosslinked for 10 min under a long wavelength UV light (365 nm) using 4-(2-hydroxyethoxy) phenyl-(2-hydroxy-2-propyl) ketone (Irgacure 2959) as photoinitiator. It was observed that as the weight feed ratio of maleic chitosan to PEGDA decreased the pore sizes of the hydrogel samples decreased, thereby increasing the densities of the hydrogel networks and producing a lower swelling ratio and a higher compressive modulus. The molecular weight of PEGDA had a similar effect. Preliminary cell cytotoxicity tests of both the maleic chitosan precursor and maleic chitosan/PEGDA hydrogels, based on the MTT assay and live-dead assay, respectively, showed that these new chitosan-based biodegradable biomaterials were relatively non-toxic to bovine aortic endothelial cells at low dosages.

The effects of heparin releasing hydrogels on vascular smooth muscle cell phenotype

Poly(ethylene glycol) diacrylate (PEGDA) hydrogel scaffolds were engineered to promote contractile smooth muscle cell (SMC) phenotype via controlled release of heparin. The scaffold design was evaluated by quantifying the effects of free heparin on SMC phenotype, engineering hydrogels to provide controlled release of heparin, and synthesizing cell-adhesive, heparin releasing hydrogels to promote contractile SMC phenotype. Heparin inhibited SMC proliferation and up-regulated expression of contractile SMC phenotype markers, including smooth muscle α-actin, calponin, and SM-22α, in a dose-dependent fashion (6 μg/ml to 3.2 mg/ml). Heparin release from PEGDA hydrogels was controlled by altering PEGDA molecular weight (MW 1000–6000) and concentration at polymerization (10–30% w/w), yielding release profiles ranging from hours to weeks in duration. Heparin released from PEGDA gels, formulated for optimized heparin loading and release kinetics (30% w/w PEGDA, MW 3000), stimulated SMCs to up-regulate contractile marker mRNA. A cell-instructive scaffold construct was prepared by polymerizing a thin hydrogel film, with pendant RGD peptides for cell attachment, over the optimized hydrogel depots. SMCs seeded on these constructs had elevated levels of contractile marker mRNA after 3 d of culture compared with SMCs on control constructs. These results indicate that RGD-modified, heparin releasing PEGDA gels can act as cell-instructive scaffolds that promote contractile SMC phenotype.

Factorial analyses of photopolymerizable thermoresponsive composite hydrogels for protein delivery

A smart protein delivery system for wound healing applications was developed using composite nanoparticle hydrogels that can release protein in a temperature-responsive manner. This system can also be formed in situ in the presence of ultraviolet light and Irgacure 2959 photoinitiator. The system consists of temperature-sensitive poly( N-isopropylacrylamide-co-acrylamide) (PNIPAM-AAm) nanoparticles embedded in a poly(ethylene glycol) diacrylate (PEGDA) matrix. A factorial analysis was performed to evaluate the effects of PEGDA concentration (10% and 15% w/v) and PEGDA molecular weight (MW; 3.4 kDa and 8 kDa), as well as PNIPAM-AAm nanoparticle concentration (2% and 4% w/v) and temperature (23°C and 40°C) on the protein release profiles and swelling ratios of the hydrogels. Results indicate that PNIPAM-AAm nanoparticle concentration and temperature were the most important factors affecting the protein release during the burst release phase. Additionally, PEGDA MW was the most important factor affecting the protein release in the plateau region. It was also important in controlling the hydrogel swelling ratio. A dual-layered hydrogel was further developed to produce a protein delivery system with a better sustained release. These findings have improved our understanding of the composite hydrogel systems and will help in tailoring future systems with desired release profiles. From the Clinical Editor A smart protein delivery system for wound healing applications using composite nanoparticle hydrogels that can release protein in a temperature-responsive manner is reported in this paper. Systems like this may aid in optimal would healing in the surgical and trauma-related settings.

In vitro degradation characteristics of photocrosslinked anhydride systems for bone augmentation applications

In the past decade, injectable biomaterials that are capable of in situ formation have garnered increased interest for use in restorative orthopedic procedures. In this study, the in vitro degradation of photocrosslinked polyanhydride matrices, derived from methacrylic anhydrides of 1,6-bis( p-carboxyphenoxy)hexane (MCPH) and sebacic acid (MSA) were evaluated over a 6-week period under physiological conditions. These matrices were augmented with two additives—the reactive diluent poly(ethylene glycol) diacrylate (PEGDA) and the buffering agent calcium carbonate (CaCO 3). Disk shaped specimens were produced by crosslinking the components using both chemical and photoinitiators and exposure to visible light. The experimental variables studied included: MCPH:MSA ratio, PEGDA molecular weight and weight fraction, and incorporation of CaCO 3. The effects of these variables on local pH, water uptake, mass loss, and mechanical properties were explored. Increasing the MCPH:MSA ratio decreased the mass loss and water uptake at predetermined endpoints, and decreased buffer acidity during degradation. Both PEGDA and CaCO 3 were found to decrease acidity and to reduce water uptake during degradation. Incorporation of CaCO 3 enabled maintenance of compressive modulus during degradation. These results demonstrate that incorporation of reactive diluents and nonreactive additives into networks of photocrosslinked anhydrides can improve system properties as a material for bone replacement.