Poly Ethylene Glycol Diacrylate Hydrogels Research Articles

Fabrication of a Monolithic Lab-on-a-Chip Platform with Integrated Hydrogel Waveguides for Chemical Sensing.

Hydrogel waveguides have found increased use for variety of applications where biocompatibility and flexibility are important. In this work, we demonstrate the use of polyethylene glycol diacrylate (PEGDA) waveguides to realize a monolithic lab-on-a-chip device. We performed a comprehensive study on the swelling and optical properties for different chain lengths and concentrations in order to realize an integrated biocompatible waveguide in a microfluidic device for chemical sensing. Waveguiding properties of PEGDA hydrogel were used to guide excitation light into a microfluidic channel to measure the fluorescence emission profile of rhodamine 6G as well as collect the fluorescence signal from the same device. Overall, this work shows the potential of hydrogel waveguides to facilitate delivery and collection of optical signals for potential use in wearable and implantable lab-on-a-chip devices.

Preliminary Study on 3D printing of PEGDA Hydrogels for Frontal Sinus Implants using Digital Light Processing (DLP)

Abstract Digital Light Processing (DLP) enables high precision 3D-printing of photopolymers and holds promising potential for patient-specific implant solutions. On the material side, Poly(ethylene glycol) diacrylate (PEGDA) has emerged as an interesting material for use in biomedical applications. For adequate photopolymerization, a photoinitiator and a light absorber are necessary, using welldefined concentrations. This study shows preliminary results of DLP 3D-printing of different PEGDA hydrogel compositions with varying water content (90; 70; 50; 30; 10; 0 % w/w) as well as varying concentrations of a photoinitiator and a light absorber. Printing performance and accuracy are investigated by printing rectangular test samples as well as an anatomically customised tubular frontal sinus implant prototype. For basic mechanical characterisation, the hardness of the printed hydrogels is investigated using a Shore A durometer. The results show a decrease in printing accuracy and hardness with an increasing water content of the composition. There is a need to use a light absorber to reach high printing accuracy. This leads to a need for increasing photoinitiator concentration and prolonged light exposure to achieve proper printing performance.

Hybrid Laser Printing of 3D, Multiscale, Multimaterial Hydrogel Structures.

Fabrication of multiscale, multi-material three-dimensional (3D) structures at high resolution is difficult using current technologies. This is especially significant when working with hydrated and mechanically weak hydrogel materials. In this work, a new hybrid laser printing (HLP) technology is reported to print complex, multiscale, multimaterial, 3D hydrogel structures with microscale resolution. This technique of fabrication utilizes sequential additive and subtractive modes of material fabrication, that are typically considered as mutually exclusive due to differences in their material processing conditions. Further, compared to current laser writing systems that enforce stringent processing depth limits, HLP is shown to fabricate structures at any depth inside the material. As a proof-of-principle, a Mayan Pyramid with embedded cube-frame is printed using model synthetic polyethylene glycol diacrylate (PEGDA) hydrogel. Printing of ready-to-use open-well chips with embedded microchannels is also demonstrated using PEGDA and gelatin methacrylate (GelMA) hydrogels for potential applications in biomedical sciences. Next, HLP is used in additive and additive modes to print multiscale 3D structures spanning in size from centimeter to micrometers within minutes, which is followed by printing of 3D, multi-material, multiscale structures using this technology. Overall, this work demonstrates that HLP's fabrication versatility can potentially offer a unique opportunity for a range of applications in optics and photonics, biomedical sciences, microfluidics, soft robotics, etc.

Keratinocytes maintain compartmentalization between dermal papilla and fibroblasts in 3D heterotypic tri-cultures.

ObjectivesReproducing human hair follicles in vitro is often limited by various reasons such as the lack of a systematic approach to culture distinct hair follicle cell types to reproduce their spatial relationship. Here, we reproduce hair follicle‐like constructs resembling the spatial orientation of different cells in vivo, to study the role of keratinocytes in maintaining cellular compartmentalization among hair follicle‐related cells.Materials and methodsDermal papilla (DP) cells, HaCaT keratinocytes and human dermal fibroblast (HDF) cells were seeded sequentially into three‐dimensional (3D) microwells fabricated from polyethylene glycol diacrylate hydrogels. Quantitative polymerase chain reaction was used to compare inductive gene expression of 3D and two‐dimensional (2D) DP. DP and HaCaT cells were transfected with green fluorescent protein and red fluorescent protein lentivirus, respectively, to enable cell visualization using confocal microscopy. ResultsThe 3D DP cultures showed significantly enhanced expression of essential DP genes as compared 2D cultures. Core‐shell configurations containing keratinocytes forming the outer shell and DP forming the core were observed. Migratory polarization was mediated by cell‐cell interaction between the keratinocytes and HDF cells, while preserving the aggregated state of the DP cells.ConclusionsKeratinocytes may play a role in maintaining compartmentalization between the DP and the surrounding HDF residing in the dermis, and therefore maintains the aggregative state of the DP cells, necessary for hair follicle development and function.

Coencapsulation of ISCs and MSCs Enhances Viability and Function of both Cell Types for Improved Wound Healing

IntroductionWe previously demonstrated that insulin secreting cells (ISCs) accelerate healing of chronic wounds, and it is known that mesenchymal stem cells (MSCs) also accelerate wound healing. Here, we report that the combination of both cell types coencapsulated into a synthetic hydrogel dressing accelerates chronic wound healing 3 × faster than control and 2 × faster than each cell type delivered singly. Specifically, insulin released by ISCs activates the PI3/Akt pathway, which is vital to the function and survival of MSCs. MSCs in turn improve the viability and function of ISCs.Materials and MethodsMSCs and/or rat islet tumor RIN-m cells were encapsulated into polyethylene glycol diacrylate hydrogel sheets and applied to 1 cm2 full thickness excisional wounds on the dorsa of genetically diabetic male mice (BKS.Cg-m +/+Leprdb/J) in accordance with protocols approved by the Rutgers IACUC. Encapsulated cell viability was assessed using a LIVE/DEAD® Viability/Cytotoxicity Kit. Akt phosphorylation, insulin, VEGF, and TGF-β1 secretion were assessed by ELISA. Animals were sacrificed on postoperative days 14 and 28 and wound tissue was collected for histological and western blot analysis.ResultsISC:MSC combination groups had the highest levels of every secreted product and phosphorylated Akt, and closed wounds in 14 days, ISC-only or MSC-only groups closed wounds in 28 days, control groups closed wounds in 40 days. Further, ISC:MSC groups healed without intermediate scab or scar.ConclusionsCombining MSCs with ISCs results in a more robust healing response than singly delivered cells, warranting further investigation of coencapsulation for MSC therapies.

Hydrophobic-force-driven adsorption of bisphenol A from aqueous solution by polyethylene glycol diacrylate hydrogel microsphere.

Polyethylene glycol diacrylate (PEGDA) hydrogel microsphere was synthesized by UV-assisted reverse emulsion polymerization as an efficient adsorbent for water purification. Optical microscopy and TEM proved its spherical and hollow structure, while XRD pattern proved that it was amorphous with limited crystallinity. Abundant oxygen-containing functional groups such as hydroxyl were detected by FTIR. The hydrogels exhibited low swelling capacities ranging from 0.19 to 0.77g/g in water and would decrease in salty solutions. The effects of operation parameters on the bisphenol A (BPA) adsorption were studied, including the polymer composition between PEGDA and polyethylene glycol methacrylate (PEGMA), initial concentration of BPA, pH, and operation temperature. The resulting hydrogel, especially for PDM2 (the ratio between PEGDA and PEGMA is 2), was able to effectively enrich BPA in water. The adsorption capacity was nearly stable below pH8.0 and decreased when beyond 8.0. Thermodynamic parameters reflected that BPA adsorbed by hydrogel was a spontaneous (ΔG0 < 0) and exothermic (ΔH0 < 0) progress. The adsorption capacity increased with the increase of the concentration of NaCl, exhibiting salinity-enhanced adsorption capacity driven by hydrophobic force. Excellent results were also achieved by applying hydrogel for spiked real surface waters, which accounted for more than 91% compared to simulated solution. As-prepared hydrogel was expected to be good candidate for treatment of endocrine disruptors with lower solubility in water.

Effective photodynamic therapy of polymer hydrogel on tumor cells prepared using methylene blue sensitized mesoporous titania nanocrystal

A novel hydrogel shell on cancer cells was prepared via in situ photopolymerization of polyethyleneglycol diacrylate (PEGDA) using methylene blue (MB) sensitized mesoporous titania nanocrystal for effective photodynamic therapy (PDT). TiO2 in this system served as an effective photosensitizer and initiator for the formation of hydrogel, also can protect the MB from being degraded into an inactive form. While MB was used as a significant photosensitive additive to improve the photochemistry effects of TiO2 and widen its optical response area to near infrared region (660–900 nm). The PEGDA hydrogel with peritumoral injectability shows competitive advantages, i.e. good biocompatibility and hydrophily, selective and minimally invasive delivery of TiO2@MB, maintaining a high PDT drug concentration for inducing tumor apoptosis, localized and sustainable release under 660 nm laser irradiation for reducing side effect. The hydrogel also could load chemo-therapy drugs, and serve as a versatile platform for multimode antitumor treatment.

Fabrication of sulphonated poly(ethylene glycol)-diacrylate hydrogel as a bone grafting scaffold.

To improve the biological performance of poly(ethylene glycol)-diacrylate (PEGDA) hydrogel as an injectable bone grafting scaffold, sodium methallyl sulphonate (SMAS) was incorporated into PEGDA hydrogel. The physiochemical properties of the resultant polymers were assessed via Fourier transform infrared spectroscopy (FTIR), swelling ratio, zeta potential, surface morphology, and protein adsorption analysis. MC3T3-E1 cells were seeded on the hydrogel to evaluate the effect of the sulphonated modification on their attachment, proliferation, and differentiation. The results of FTIR and zeta potential evaluations revealed that SMAS was successfully incorporated into PEGDA. With increasing concentrations of SMAS, the swelling ratio of the hydrogels increased in deionized water but stayed constant in phosphate buffered saline. The protein adsorption also increased with increasing concentration of SMAS. Moreover, the sulphonated modification of PEGDA hydrogel not only enhanced the attachment and proliferation of osteoblast-like MC3T3-E1 cells but also up-regulated alkaline phosphatase activity as well as gene expression of osteogenic markers and related growth factors, including collagen type I, osteocalcin, runt related transcription factor 2, bone morphogenetic protein 2, and transforming growth factor beta 1. These findings indicate that the sulphonated modification could significantly improve the biological performance of PEGDA hydrogel. Thus, the sulphonated PEGDA is a promising scaffold candidate for bone grafting.

Biphasic osteochondral scaffold fabrication using multi-material mask projection stereolithography

PurposeThis study aims to develop a multi-material stereolithography (MMSL) technique to directly fabricate a biphasic osteochondral scaffold.Design/methodology/approachA bespoke prototype MMSL system was developed based on a bottom-up mask projection approach. The system was controlled by a multi-material fabrication algorithm with minimum number of switching cycles during fabrication. A variable-power light source was used to fabricate materials with significantly different curing characteristics. The light-curable poly(ethylene glycol) diacrylate (PEGDA) hydrogel and beta-tricalcium phosphate (β-TCP) ceramic suspension were used for fabricating the biphasic osteochondral scaffold.FindingsThe bonding strength of the multi-material interface is shown to be mainly affected by the type of photopolymer, rather than the switching of the materials in MMSL. Lighting power densities of 2.64 and 14.98 mW/cm2 were used for curing the PEGDA hydrogel and the ß-TCP ceramic suspension, respectively. A biphasic osteochondral scaffold with complex interface was successfully fabricated.Originality/valueThis study proposes a potential technical method (MMSL) for manufacturing a complex biphasic osteochondral scaffold composing a PEGDA hydrogel/ß-TCP ceramic composite in a time-efficient and precise manner. The designed bone-cartilage scaffold interface and the surface of the cartilage scaffold can be precisely manufactured.

Fabrication of nanocellulose/PEGDA hydrogel by 3D printing

PurposeNanocellulose is characterised by favourable biocompatibility, degradability, nanostructure effect, high modulus and high tensile strength and has been widely applied in various fields. The current research in the field of new nanocellulose materials mainly focuses on the hydrogel, aerogel and the tissue engineering scaffold. All of these are three-dimensional (3D) porous materials, but conventional manufacturing technology fails to realise precise control. Therefore, the method of preparing structural materials using 3D printing and adopting the nanocellulose as the 3D printing material has been proposed. Then, how to realise 3D printing of nanocellulose is the problem that should be solved.Design/methodology/approachBy adding the photosensitive component polyethyleneglycol diacrylate (PEGDA) in the aqueous dispersion system of nanocellulose, the nanocellulose was endowed with photosensitivity. Then, nanocellulose/PEGDA hydrogels were prepared by the additive manufacturing of nanocellulose through light curing.FindingsThe results showed that the nanocellulose/PEGDA hydrogels had a uniform shape and a controllable structure. The nanocellulose supported the scaffold structure in the hydrogels. Prepared with 1.8 per cent nanocellulose through 40 s of light curing, the nanocellulose/PEGDA hydrogels had a maximum compression modulus of 0.91 MPa. The equilibrium swelling ratio of the nanocellulose/PEGDA hydrogel prepared with 1.8 per cent nanocellulose was 13.56, which increased by 44 per cent compared with that of the PEGDA hydrogel without nanocellulose.Originality/valueThe paper proposed a method for rapidly prototyping the nanocellulose with expected properties, which provided a theoretical basis and technological reference for the 3D additive manufacturing of nanocellulose 3D structure materials with a controlled accurate architecture.

Effect of water concentration on the shock response of polyethylene glycol diacrylate (PEGDA) hydrogels: A molecular dynamics study

Shockwave propagation in polyethylene glycol diacrylate (PEGDA) hydrogels is simulated for the first time using nonequilibrium molecular dynamics simulations. PEGDA hydrogel models are built using the “perfect network” approach such that each crosslink junction is comprised of six chain connections. The influence of PEGDA concentration (20–70 wt%) on shock behavior is investigated for a range of particle velocities (200–1000 m/s). In agreement with reported experimental results in the literature on gels with similar densities, shock velocity and pressure in PEGDA hydrogels are found to increase with polymer concentration, within a range bounded by pure water and pure polymer behaviors. Nonlinear relationships are observed for shock pressure and shock front thickness as a function of concentration, and a logarithmic equation is proposed to describe this behavior. In addition, the relationship between pressure and shock front thickness is compared with hydrodynamic theory. Deviation from hydrodynamic predictions is observed at high particle velocities and this deviation is found to be related to viscosity changes. A power-law relationship between strain rate and pressure in PEGDA hydrogels is identified, similar to that of metals. However, a power-law exponent of 1.4 is computed for all gel concentrations, whereas an exponent of 4 is typically reported for metals.

Fabrication of Functional Biomaterial Microstructures by in Situ Photopolymerization and Photodegradation.

The in situ fabrication of poly(ethylene glycol) diacrylate (PEGDA) hydrogel microstructures within poly(dimethylsiloxane) (PDMS)-based microfluidic networks is a versatile technique that has enabled unique applications in biosensing, medical diagnostics, and the fundamental life sciences. Hydrogel structures have previously been patterned by the lithographic photopolymerization of PEGDA hydrogel forming solutions, a process that is confounded by oxygen-permeable PDMS. Here, we introduce an alternate PEG patterning technique that relies upon the optical sculpting of features by patterned light-induced erosion of photodegradable PEGDA deemed negative projection lithography. We quantitatively compared the hydrogel micropatterning fidelity of negative projection lithography to positive projection lithography, using traditional PEGDA photopolymerization, within PDMS devices. We found that the channel depth, the local oxygen atmosphere, and the UV exposure time dictated the size and resolution of hydrogel features formed using positive projection lithography. In contrast, negative projection lithography was observed to deliver high-resolution functional features with dimensions on the order of single micrometers enabled by its facilely controlled mechanism of feature formation that is insensitive to oxygen. Next, the utility of photodegradable PEGDA was further assessed by encapsulating or conjugating bioactive molecules within photodegradable PEG matrixes to provide a route to the formation of complex and dynamically reconfigurable chemical microenvironments. Finally, we demonstrated that negative projection lithography enabled photopatterning of multilayered microscale objects without the need for precise mask alignment. The described approach for photopatterning high-resolution photolabile hydrogel microstructures directly within PDMS microchannels could enable novel microsystems of increasing complexity and sophistication for a variety of clinical and biological applications.

The effect of polymer molecular weight and cell seeding density on viability of cells entrapped within PEGDA hydrogel microspheres

Cell microencapsulation can be used in tissue engineering as a scaffold or physical barrier that provides immunoisolation for donor cells. When used as a barrier, microencapsulation shields donor cells from the host immune system when implanted for cell therapies. Maximizing therapeutic product delivery per volume of microencapsulated cells necessitates first optimising the viability of entrapped cells. Although cell microencapsulation within alginate is well described, best practices for cell microencapsulation within polyethylene glycol is still being elucidated. In this study we microencapsulate mouse preosteoblast cells within polyethylene glycol diacrylate (PEGDA) hydrogel microspheres of varying molecular weight or seeding densities to assess cell viability in relation to cell density and polymer molecular weight. Diffusion studies revealed molecule size permissible by each molecular weight PEGDA towards correlating viability with polymer mesh size. Results demonstrated higher cell viability in higher molecular weight PEGDA microspheres and when cells were seeded at higher cell densities.

Engineering biologically extensible hydrogels using photolithographic printing

Biomaterials for tissue engineering that recapitulate the mechanical response and biological function of native tissue are highly sought after to lessen the burden of damaged or diseased tissue. Poly(ethylene glycol) diacrylate (PEGDA) hydrogels are a popular candidate because of their favorable bioactive properties. However, their mechanical behavior is very dissimilar to that of biological tissue, which behaves in a mechanically anisotropic, nonlinear, and viscoelastic fashion. It has been previously shown that PEGDA hydrogels can be patterned in alternating linear strips of different stiffnesses to generate anisotropic behavior, but these constructs still have a linear stress-strain response. In this study, we imparted nonlinear mechanical properties to PEGDA hydrogels by fabricating composite hydrogel constructs consisting of a stiff sinusoidal reinforcement embedded into a softer base matrix. This was achieved by polymerizing low molecular weight (MW) PEGDA hydrogel precursor into a stiff sinusoidal shape and then polymerizing this construct into a high MW precursor. Samples were generated with different relative stiffness between the two components and a range of sinusoid periodicities to assess the tunability of the resulting stress-strain curve. Tensile testing indicates that the sinusoidal patterning gives rise to nonlinear stress-strain behavior. Varying the relative stiffness was shown to tune the slope of the linear region of the stress-strain curve, and varying periodicity was shown to affect the length of the toe region of this curve. We conclude that composite hydrogels with stiff sinusoidally-patterned reinforcements display mechanical properties more similar to those of biological tissue than uniform or linearly-patterned hydrogels. Statement of SignificanceHydrogel biomaterials are a popular candidate for engineering constructs that can mimic the properties of native tissue for disease modeling and tissue-engineering applications. Studies have shown that poly(ethylene) glycol diacrylate (PEGDA) hydrogels can be fabricated to display many biological aspects of native tissue. However, they are unable to recapitulate fundamental mechanical properties of such tissue, such as anisotropy and nonlinearity. Photolithographic techniques have been employed to generate anisotropic linear PEGDA hydrogels via patterned reinforcement. The present study indicates that such techniques can be modified to generate PEGDA constructs with a sinusoidal reinforcement that display a strongly nonlinear response to tensile loading. This work sets the stage for more intricate patterning for providing increased control over hydrogel mechanical response.

Influence of polymerization conditions on the refractive index of poly(ethylene glycol) diacrylate (PEGDA) hydrogels

This paper studies the influences of fabrication parameters on the optical properties of poly(ethylene glycol) diacrylate(PEGDA) hydrogels during polymerization, including the irradiation intensity, irradiation time, photoinitiator concentration, and water content. The refractive index of PEGDA hydrogels polymerized under various conditions is measured, with the results shown to be valuable for future research applying PEGDA hydrogels as optical materials. In addition, it is found that the photoinitiator concentration used can be as low as 1.0 wt%, which is severalfold lower than that previously reported, making PEGDA hydrogels more desirable for bioapplications.

Human iPSC-derived mesenchymal stem cells encapsulated in PEGDA hydrogels mature into valve interstitial-like cells

Despite recent advances in tissue engineered heart valves (TEHV), a major challenge is identifying a cell source for seeding TEHV scaffolds. Native heart valves are durable because valve interstitial cells (VICs) maintain tissue homeostasis by synthesizing and remodeling the extracellular matrix. This study demonstrates that induced pluripotent stem cells (iPSC)-derived mesenchymal stem cells (iMSCs) can be derived from iPSCs using a feeder-free protocol and then further matured into VICs by encapsulation within 3D hydrogels. The differentiation efficiency was characterized using flow cytometry, immunohistochemistry staining, and trilineage differentiation. Using our feeder-free differentiation protocol, iMSCs were differentiated from iPSCs and had CD90+, CD44+, CD71+, αSMA+, and CD45− expression. Furthermore, iMSCs underwent trilineage differentiation when cultured in induction media for 21 days. iMSCs were then encapsulated in poly(ethylene glycol)diacrylate (PEGDA) hydrogels grafted with adhesion peptide (RGDS) to promote remodeling and further maturation into VIC-like cells. VIC phenotype was assessed by the expression of alpha-smooth muscle actin (αSMA), vimentin, and collagen production after 28 days. When MSC-derived cells were encapsulated in PEGDA hydrogels that mimic the leaflet modulus, a decrease in αSMA expression and increase in vimentin was observed. In addition, iMSCs synthesized collagen type I after 28 days in 3D hydrogel culture. Thus, the results from this study suggest that iMSCs may be a promising cell source for TEHV. Statement of SignificanceDeveloping a suitable cell source is a critical component for the success and durability of tissue engineered heart valves. The significance of this study is the generation of iPSCs-derived mesenchymal stem cells (iMSCs) that have the capacity to mature into valve interstitial-like cells when introduced into a 3D cell culture designed to mimic the layers of the valve leaflet. iMSCs were generated using a feeder-free protocol, which is one major advantage over other methods, as it is more clinically relevant. In addition to generating a potential new cell source for heart valve tissue engineering, this study also highlights the importance of a 3D culture environment to influence cell phenotype and function.

A bilayer swellable drug-eluting ureteric stent: Localized drug delivery to treat urothelial diseases

A bilayer swellable drug-eluting ureteric stent (BSDEUS) is engineered and implemented, as a sustained drug delivery platform technology that enhances localized drug delivery to the highly impermeable urothelium, for the treatment of urothelial diseases such as strictures and carcinomas. On deployment, the device swells to co-apt with the ureteric wall and ensure drug availability to these tissues.BSDEUS consists of a stent spray-coated with a polymeric drug containing polylactic acid-co-caprolactone (PLC) layer which is overlaid by a swellable polyethylene glycol diacrylate (PEGDA) based hydrogel.In-vitro quantification of released drug demonstrated a tunable time-profile, indicating sustained delivery over 1-month. The PEGDA hydrogel overlayer enhanced drug release and transport into explanted porcine ureteric tissues ex-vivo, under a simulated dynamic fluid flow. A preliminary pilot in-vivo feasibility study, in a porcine model, demonstrated that the swollen hydrogel co-apts with the urothelium and thus enables localized drug delivery to the target tissue section. Kidney functions remained unaffected and device did not result in either hydronephrosis or systemic toxicity.This successful engineering of a bilayer coated stent prototype, demonstrates its feasibility, thus offering a unique solution for drug-based urological therapy.

Drug Delivered Poly(ethylene glycol) Diacrylate (PEGDA) Hydrogels and Their Mechanical Characterization Tests for Tissue Engineering Applications

AbstractTissue Engineering has been studied to develop tissues as an alternative approach to the organ regeneration. Successful artificial tissue growth in regenerative medicine depends on the precise scaffold fabrication as well as the cell-cell and cell-scaffold interaction. Scaffolds are extracellular matrices that guide cells to grow in 3D to regenerate the tissues. Cell-seeded scaffolds must be implanted to the damaged tissues to do the tissue regeneration. Scaffolds’ mechanical properties and porosities are the two main scaffold fabrication parameters as the scaffolds must be able to hold the pressure due to the surrounding tissues after the implantation process. In this research, scaffolds were fabricated by photolithography and Poly(ethylene glycol) Diacrylate (PEGDA) which is a biocompatible and biodegradable material was used as a fabrication material. In order to compare the compressive properties of PEGDA only with the compressive properties of drug delivered PEGDA, firstly, PEGDA only solutions were prepared. Then, PEGDA was mixed with Meloxicam 15 mg, Hydrochlorothiazide 12.5 mg, Cyclobenzaprine 10 mg and Spironolactone-hctz 25-25 mg respectively and they were placed under the UV light for about 15 minutes to solidify the cylindrical shaped hydrogels. 5 samples from each group were fabricated under the same conditions. Laboratory temperature, photoinitiator concentration and UV light intensity was kept constant during the fabrication process. After the fabrication was completed, Instron 3369 universal mechanical testing machine with the 5 mm/min compression rate was used to do the compression tests to compare the drug effects on PEGDA hydrogels. Our results indicate that average ultimate strength of PEGDA only samples was 3.820 MPa. Also, due to the fact that Meloxicam 15 mg and PEGDA mixture did not solidify under the UV light at all, compression test could not be performed for PEGDA- Meloxicam 15 mg mixture. However, Hydrochlorothiazide 12.5 mg, Cyclobenzaprine 10 mg and Spironolactone-hctz 25-25 mg dissolved within the PEGDA completely and our compression results show that average ultimate strengths were 3.372 MPa, 1.602 MPa, 1.999 MPa respectively. This preliminary research showcases that compressive properties of the PEGDA-based photopolymerized scaffolds can be altered with the control of the drug type and drug concentration.

Covalent incorporation of tobacco mosaic virus increases the stiffness of poly(ethylene glycol) diacrylate hydrogels.

Hydrogels are versatile materials, finding applications as adsorbers, supports for biosensors and biocatalysts or as scaffolds for tissue engineering. A frequently used building block for chemically cross-linked hydrogels is poly(ethylene glycol) diacrylate (PEG-DA). However, after curing, PEG-DA hydrogels cannot be functionalized easily. In this contribution, the stiff, rod-like tobacco mosaic virus (TMV) is investigated as a functional additive to PEG-DA hydrogels. TMV consists of more than 2000 identical coat proteins and can therefore present more than 2000 functional sites per TMV available for coupling, and thus has been used as a template or building block for nano-scaled hybrid materials for many years. Here, PEG-DA (Mn = 700 g mol−1) hydrogels are combined with a thiol-group presenting TMV mutant (TMVCys). By covalent coupling of TMVCys into the hydrogel matrix via the thiol-Michael reaction, the storage modulus of the hydrogels is increased compared to pure PEG-DA hydrogels and to hydrogels containing wildtype TMV (wt-TMV) which is not coupled covalently into the hydrogel matrix. In contrast, the swelling behaviour of the hydrogels is not altered by TMVCys or wt-TMV. Transmission electron microscopy reveals that the TMV particles are well dispersed in the hydrogels without any large aggregates. These findings give rise to the conclusion that well-defined hydrogels were obtained which offer the possibility to use the incorporated TMV as multivalent carrier templates e.g. for enzymes in future studies.

Hydrogel micropost-based qPCR for multiplex detection of miRNAs associated with Alzheimer's disease

Quantitative polymerase chain reaction (qPCR) renders profiling of genes of interest less time-consuming and cost-effective. Recently, multiplex profiling of miRNAs has enabled identifying or investigating predominant miRNAs for various diseases such as cancers and neurodegenerative diseases. Conventional multiplex qPCR technologies mostly use colorimetric measurements in solution phase, yet not only suffer from limited multiplexing capacity but also require target-screening processes due to non-specific binding between targets and primers. Here, we present hydrogel micropost-based qPCR for multiplex detection of miRNAs associated with Alzheimer's disease (AD). Our methodology promises two key advantages compared with the conventional solution-based PCR: 1) nearly no non-specific crosstalks between targets and primers, and 2) practically valuable multiplexing by spatial encoding within a single microchamber. Specifically, we immobilized hydrogel microposts (~ 400µm in diameter) within commercially available polycarbonate PCR chips by multi-step ultraviolet (UV, 365nm) exposure. We optimized this photoimmobilization for thermal cycles of PCR as well. Acrylated forward primers incorporated in polyethylene glycol diacrylate (PEGDA) posts played a crucial role to confine fluorescent signal of cDNA amplification within the PEGDA hydrogel. To demonstrate the potential of our platform, we successfully verified multiplex detection of five miRNAs, which were reported to be highly correlated with AD, from a complex buffer of human plasma.