Patterning porosity in hydrogels by arresting phase separation

Poly (ethylene glycol) (PEG) hydrogels have been used extensively in biological and tissue engineering, because of their outstanding biocompatibility and processability. However, it is not yet possible to process soft materials like PEG hydrogels with the requisite precision and throughput needed to recapitulate macroscopic biological tissue with control over every hierarchical scale. In this study, porous PEG hydrogels are processed by a phase separation method and patterned in a single photolithographic step. The thermodynamics of the temperature triggered spinodal decomposition of a ternary mixture of water, salt, and polymer are studied resulting in a ternary phase diagram and a spinodal temperature plot. Importantly, the state of porosity can be frozen by exposing the hydrogel to UV light to form a crosslinked hydrogel network. The average pore size can be tuned by changing delay between the application of heat and UV exposure. By utilizing grey-scale photomasks, a single process can be used to define regions of pure hydrogel, porous hydrogel with a programmed average pore size, and blank substrate with no hydrogel. In addition to representing a combination of a top-down and a bottom-up processes that enables the realization of complex samples, the simplicity of this process and the versatility of the resultant patterns could provide a useful capability for the definition of hydrogel samples for the development of advanced biomaterials

Micro-fabrication of Carbon Structures by Pattern Miniaturization in Resorcinol-Formaldehyde Gel

A simple and novel method to fabricate and miniaturize surface and sub-surface micro-structures and micro-patterns in glassy carbon is proposed and demonstrated. An aqueous resorcinol-formaldehyde (RF) sol is employed for micro-molding of the master-pattern to be replicated, followed by controlled drying and pyrolysis of the gel to reproduce an isotropically shrunk replica in carbon. The miniaturized version of the master-pattern thus replicated in carbon is about one order of magnitude smaller than original master by repeating three times the above cycle of molding and drying. The micro-fabrication method proposed will greatly enhance the toolbox for a facile fabrication of a variety of Carbon-MEMS and C-microfluidic devices.Comment: 16 pages, 5 figure

Hydrogel-Based Colorimetric Assay for Multiplexed MicroRNA Detection in a Microfluidic Device

Although microRNA (miRNA) expression levels provide important information regarding disease states owing to their unique dysregulation patterns in tissues, translation of miRNA diagnostics into point-of-care (POC) settings has been limited by practical challenges. Her; we developed a hydrogel-based microfluidic platform for colorimetric profiling of miRNAs, without the use of complex external equipment for fluidics and imaging. For sensitive and reliable measurement without the risk of sequence bias, we employed a gold deposition-based signal amplification scheme and dark-field imaging, and seamlessly integrated a previously developed miRNA assay scheme into this platform. The assay demonstrated a limit of detection of 260 fM, along with multiplexing of small panels of miRNAs in healthy and cancer samples. We anticipate this versatile platform to facilitate a broad range of POC profiling of miRNAs in cancer-associated dysregulation with high-confidence by exploiting the unique features of hydrogel substrate in an on-chip format and colorimetric analysis

Layered Fabrication of Branched Networks Using Lindenmayer Systems

A current challenge impeding the growth of bone tissue engineering is the lack of functional scaffolds of geometric sizes greater than 10mm due to the inability of cells to survive deep within the scaffold. It is hypothesized that these scaffolds must have an inbuilt nutrient distribution network to sustain the uniform growth of cells. In this paper, we seek to enhance the design and layered fabrication of scaffold internal architecture through the development of Lindenmayer systems, a graphical language based theory to create nutrient delivery networks. The scaffolds are fabricated using the Texas Instruments DLP™ system through UV‐photopolymerization to produce polyethylene glycol hydrogels with internal branch structures. The paper will discuss the Lindenmayer system, process planning algorithms, layered fabrication of samples, challenges and future tasks.Mechanical Engineerin

UV-Photolithography Fabrication of Poly-Ethylene Glycol Hydrogels Encapsulated with Hepatocytes

The development of biomanufacturing technologies particularly, layered manufacturing has advanced cell encapsulation processes in an effort to mimic the cellular microenvironment for invitro studies. This paper illustrates an inexpensive UV-photolithographic method for encapsulation of human hepatocytes in three dimensional structures using poly-ethylene diacrylate (PEGDA) hydrogels as candidate substrates. In order to further develop this technology for layered fabrication, we have quantified the long-term effects of the photo-initiator concentration and UV light exposure on the metabolic rates of encapsulated human hepatocytes under a 21 day study. The photoinitator toxicity was observed immediately after polymerization with no significant cytotoxicity on a long term basis. A cellular viability is examined and reported for the UV photopolymerization process. Cell phenotype maintenance was observed by measuring the amount of urea produced over a 1 week time period. This photo encapsulation process may find use in the fabrication of spatially complex 3D scaffolds for tissue engineering applications, elucidation of the 3D structure-pharmacokinetic response relationship and the fabrication of complex multi-compartment liver tissue analog devices for drug screening applications.Mechanical Engineerin

Prescribed pattern transformation in swelling gel tubes by elastic instability

We present a study on swelling-induced circumferential buckling of tubular shaped gels. Inhomogeneous stress develops as gel swells under mechanical constraints, which gives rise to spontaneous buckling instability without external force. Full control over the post-buckling pattern is experimentally demonstrated. A simple analytical model is developed using elastic energy to predict stability and post-buckling patterns upon swelling. Analysis reveals that height to diameter ratio is the most critical design parameter to determine buckling pattern, which agrees well with experimental and numerical results.Comment: 32 pages, 7 figure

Design and in Vitro Evaluation of a New Nano-Microparticulate System for Enhanced Aqueous-Phase Solubility of Curcumin

Curcumin, a yellow polyphenol derived from the turmeric Curcuma longa, has been associated with a diverse therapeutic potential including anti-inflammatory, antioxidant, antiviral, and anticancer properties. However, the poor aqueous solubility and low bioavailability of curcumin have limited its potential when administrated orally. In this study, curcumin was encapsulated in a series of novel nano-microparticulate systems developed to improve its aqueous solubility and stability. The nano-microparticulate systems are based entirely on biocompatible, biodegradable, and edible polymers including chitosan, alginate, and carrageenan. The particles were synthesized via ionotropic gelation. Encapsulating the curcumin into the hydrogel nanoparticles yielded a homogenous curcumin dispersion in aqueous solution compared to the free form of curcumin. Also, the in vitro release profile showed up to 95% release of curcumin from the developed nano-microparticulate systems after 9 hours in PBS at pH 7.4 when freeze-dried particles were used.CONACYTCUPIAPharmac

Simple one pot preparation of chemical hydrogels from cellulose dissolved in cold LiOH/urea

In this work, non-derivatized cellulose pulp was dissolved in a cold alkali solution (LiOH/urea) and chemically cross-linked with methylenebisacrylamide (MBA) to form a robust hydrogel with superior water absorption properties. Different cellulose concentrations (i.e., 2, 3 and 4 wt%) and MBA/glucose molar ratios (i.e., 0.26, 0.53 and 1.05) were tested. The cellulose hydrogel cured at 60 °C for 30 min, with a MBA/glucose molar ratio of 1.05, exhibited the highest water swelling capacity absorbing ca. 220 g H2O/g dry hydrogel. Moreover, the data suggest that the cross-linking occurs via a basic Michael addition mechanism. This innovative procedure based on the direct dissolution of unmodified cellulose in LiOH/urea followed by MBA cross-linking provides a simple and fast approach to prepare chemically cross-linked non-derivatized high-molecular-weight cellulose hydrogels with superior water uptake capacity.Portuguese Foundation for Science and Technology, FCT, via the projects PTDC/AGR-TEC/4814/2014, PTDC/ASP-SIL/30619/2017 and UIDB/05183/2020, and the research grant IF/01005/2014.info:eu-repo/semantics/publishedVersio