Hydrocolloids of Egg White and Gelatin as a Platform for Hydrogel-Based Tissue Engineering.

Innovative materials are needed to produce scaffolds for various tissue engineering and regenerative medicine (TERM) applications, including tissue models. Materials derived from natural sources that offer low production costs, easy availability, and high bioactivity are highly preferred. Chicken egg white (EW) is an overlooked protein-based material. Whilst its combination with the biopolymer gelatin has been investigated in the food technology industry, mixed hydrocolloids of EW and gelatin have not been reported in TERM. This paper investigates these hydrocolloids as a suitable platform for hydrogel-based tissue engineering, including 2D coating films, miniaturized 3D hydrogels in microfluidic devices, and 3D hydrogel scaffolds. Rheological assessment of the hydrocolloid solutions suggested that temperature and EW concentration can be used to fine-tune the viscosity of the ensuing gels. Fabricated thin 2D hydrocolloid films presented globular nano-topography and in vitro cell work showed that the mixed hydrocolloids had increased cell growth compared with EW films. Results showed that hydrocolloids of EW and gelatin can be used for creating a 3D hydrogel environment for cell studies inside microfluidic devices. Finally, 3D hydrogel scaffolds were fabricated by sequential temperature-dependent gelation followed by chemical cross-linking of the polymeric network of the hydrogel for added mechanical strength and stability. These 3D hydrogel scaffolds displayed pores, lamellae, globular nano-topography, tunable mechanical properties, high affinity for water, and cell proliferation and penetration properties. In conclusion, the large range of properties and characteristics of these materials provide a strong potential for a large variety of TERM applications, including cancer models, organoid growth, compatibility with bioprinting, or implantable devices.

Collagen-Laponite Nanoclay Hydrogels for Tumor Spheroid Growth.

The extracellular matrix (ECM) plays an important regulatory role in the development and progression of tumoral tissue. Its functions and properties are crucial in determining tumor cell behavior such as invasion, migration, and malignancy development. Our study explores the role of collagen type I in cancer development and spread using engineered tumor models like multicellular spheroids grown in collagen-based hydrogels to simulate early tumor formation. We employ microfluidic techniques to test the hypothesis that (i) adding Laponite nanoclay to collagen hydrogels modifies mechanical and rheological properties and (ii) changing the stiffness of the collagen microenvironment affects tumor spheroid growth. Our findings support our theories and suggest the use of ECM components and engineered tumor models in cancer research, offering a biocompatible and biomimetic method to tailor the mechanical properties of conventional collagen hydrogels.

Improved Copper-Epoxy Adhesion by Laser Micro- and Nano-Structuring of Copper Surface for Thermal Applications.

The objective of this work is the enhancement of metal-to-metal bonding to provide high thermal conductivity together with electrical insulation, to be used as heat sinks at room and cryogenic temperatures. High thermal conductive metal (copper) and epoxy resin (Stycast 2850FT) were used in this study, with the latter also providing the required electrical insulation. The copper surface was irradiated with laser to induce micro- and nano-patterned structures that result in an improvement of the adhesion between the epoxy and the copper. Thus, copper-to-copper bonding strength was characterized by means of mechanical tensile shear tests. The effect of the laser processing on the thermal conductivity properties of the Cu/epoxy/Cu joint at different temperatures, from 10 to 300 K, is also reported. Using adequate laser parameters, it is possible to obtain high bonding strength values limited by cohesive epoxy fracture, together with good thermal conductivity at ambient and cryogenic temperatures.

Reduction in Processing Time in Ca3Co4O9+δ Ceramics through Nanoprecursors Produced by an Easily Scalable and Environmentally Friendly Process.

Attrition milling is an easily scalable and environmentally friendly process used to produce Ca3Co4O9+δ nanoprecursors in a relatively short time. Sintered materials produced through the classical solid-state method, involving ball milling, show much larger grain sizes and slightly lower density than those obtained in samples produced from attrition-milled precursors. On the other hand, electrical resistivity has been drastically decreased, accompanied with a slight decrease in the Seebeck coefficient in samples obtained from these attrition-milled precursors. Moreover, the use of an attrition milling process leads to a very important reduction in processing time (around 75%), together with a slight power factor improvement of around 10%, when compared to the classically prepared samples.

The use of mixed collagen-Matrigel matrices of increasing complexity recapitulates the biphasic role of cell adhesion in cancer cell migration: ECM sensing, remodeling and forces at the leading edge of cancer invasion.

The migration of cancer cells is highly regulated by the biomechanical properties of their local microenvironment. Using 3D scaffolds of simple composition, several aspects of cancer cell mechanosensing (signal transduction, EMC remodeling, traction forces) have been separately analyzed in the context of cell migration. However, a combined study of these factors in 3D scaffolds that more closely resemble the complex microenvironment of the cancer ECM is still missing. Here, we present a comprehensive, quantitative analysis of the role of cell-ECM interactions in cancer cell migration within a highly physiological environment consisting of mixed Matrigel-collagen hydrogel scaffolds of increasing complexity that mimic the tumor microenvironment at the leading edge of cancer invasion. We quantitatively show that the presence of Matrigel increases hydrogel stiffness, which promotes ß1 integrin expression and metalloproteinase activity in H1299 lung cancer cells. Then, we show that ECM remodeling activity causes matrix alignment and compaction that favors higher tractions exerted by the cells. However, these traction forces do not linearly translate into increased motility due to a biphasic role of cell adhesions in cell migration: at low concentration Matrigel promotes migration-effective tractions exerted through a high number of small sized focal adhesions. However, at high Matrigel concentration, traction forces are exerted through fewer, but larger focal adhesions that favor attachment yielding lower cell motility.

Combined experimental and computational characterization of crosslinked collagen-based hydrogels.

Collagen hydrogels are widely used for in-vitro experiments and tissue engineering applications. Their use has been extended due to their biocompatibility with cells and their capacity to mimic biological tissues; nevertheless their mechanical properties are not always optimal for these purposes. Hydrogels are formed by a network of polymer filaments embedded on an aqueous substrate and their mechanical properties are mainly defined by the filament network architecture and the individual filament properties. To increase properties of native collagen, such as stiffness or strain-stiffening, these networks can be modified by adding crosslinking agents that alter the network architecture, increasing the unions between filaments. In this work, we have investigated the effect of one crosslinking agent, transglutaminase, in collagen hydrogels with varying collagen concentration. We have observed a linear dependency of the gel rigidity on the collagen concentration. Moreover, the addition of transglutaminase has induced an earlier strain-stiffening of the collagen gels. In addition, to better understand the mechanical implications of collagen concentration and crosslinkers inclusion, we have adapted an existing computational model, based on the worm-like chain model (WLC), to reproduce the mechanical behavior of the collagen gels. With this model we can estimate the parameters of the biopolymer networks without more sophisticated techniques, such as image processing or network reconstruction, or, inversely, predict the mechanical properties of a defined collagen network.