Matrix design for optimal pancreatic ß cells transplantation.

New therapeutic approaches to treat type 1 diabetes mellitus relies on pancreatic islet transplantation. Here, developing immuno-isolation strategies is essential to eliminate the need for systemic immunosuppression after pancreatic islet grafts. A solution is the macro-encapsulation of grafts in semipermeable matrixes with a double function: separating islets from host immune cells and facilitating the diffusion of insulin, glucose, and other metabolites. This study aims to synthesize and characterize different types of gelatin-collagen matrixes to prepare a macro-encapsulation device for pancreatic islets that fulfill these functions. While natural polymers exhibit superior biocompatibility compared to synthetic ones, their mechanical properties are challenging to reproduce. To address this issue, we conducted a comparative analysis between photo-crosslinked gelatin matrixes and chemically crosslinked collagen matrixes. We show that the different crosslinkers and polymerization methods influence the survival and glucose-stimulated insulin production of pancreatic ß cells (INS1) in vitro, as well as the in vitro and in vivo stability of the matrix and the immuno-isolation in vivo. Among the matrixes, the stiff multilayer GelMA matrixes (8.5 kPa), fabricated by digital light processing, were the best suited for pancreatic ß cells macro-encapsulation regarding these parameters. Within the alveoli of this matrix, pancreatic ß cells spontaneously formed aggregates.

Ductile-to-brittle transition and yielding in soft amorphous materials: perspectives and open questions.

Soft amorphous materials are viscoelastic solids ubiquitously found around us, from clays and cementitious pastes to emulsions and physical gels encountered in food or biomedical engineering. Under an external deformation, these materials undergo a noteworthy transition from a solid to a liquid state that reshapes the material microstructure. This yielding transition was the main theme of a workshop held from January 9 to 13, 2023 at the Lorentz Center in Leiden. The manuscript presented here offers a critical perspective on the subject, synthesizing insights from the various brainstorming sessions and informal discussions that unfolded during this week of vibrant exchange of ideas. The result of these exchanges takes the form of a series of open questions that represent outstanding experimental, numerical, and theoretical challenges to be tackled in the near future.

Interplay between wall slip and shear banding in a thixotropic yield stress fluid.

We study the local dynamics of a thixotropic yield stress fluid that shows a pronounced non-monotonic flow curve. This mechanically unstable behavior is generally not observable from standard rheometry tests, resulting in a stress plateau that stems from the coexistence of a flowing band with an unyielded region below a critical shear rate c. Combining ultrasound velocimetry with standard rheometry, we discover an original shear-banding scenario in the decreasing branch of the flow curve of model paraffin gels, in which the velocity profile of the flowing band is set by the applied shear rate  instead of c. As a consequence, the material slips at the walls with a velocity that shows a non-trivial dependence on the applied shear rate. To capture our observations, we propose a differential version of the so-called lever rule, describing the extent of the flowing band and the evolution of wall slip with shear rate. This phenomenological model holds down to very low shear rates, at which the dimension of the flowing band becomes comparable to the size of the individual wax particles that constitute the gel microstructure, leading to cooperative effects. Our approach provides a framework where constraints imposed in the classical shear-banding scenario can be relaxed, with wall slip acting as an additional degree of freedom.

Gelatine-collagen photo-crosslinkable 3D matrixes for skin regeneration.

Immediate care of skin wounds and burns is essential to repair this mechanical and chemical barrier to infections. Hydrogels have become one of the standard methods for wound care. Here, gelatine-collagen photo-crosslinkable matrixes or hydrogels were manufactured by two-photon polymerization (TPP) or one-photon UV exposure using a Digital Light Processing (DLP) setup. Both techniques are able to construct matrixes from computer-aided design models, which is important for future clinical applications in which wound dressings should be customized. Although TPP can mimic the 3D dermo-epidermal junction with a high spatial resolution (i.e., ∼6 µm3), the manufacturing time was too slow to produce large wound dressings. Therefore, a DLP setup was explored in this study to fabricate large 2D matrixes of several cm2 using the same photo-resist as for TPP, except for the photoinitiator. The fibroblast viability, adherence, and proliferation were analysed in time on both 3D and 2D matrixes in vitro using two-photon microscopy. For both types of matrixes, the adherence and proliferation of fibroblasts (3T3-NIH) were optimal for stiff structures with a Young's modulus of 191 ± 35 kPa compared to softer matrixes of 37 ± 12 kPa. Fibroblast showed complete confluence on Day 14 after seeding on these matrixes, which may create the granulation tissue composed of fibronectin, collagen, and various proteoglycans in the future dermis before repair of the epidermis and disintegrating of their host matrix. For the monitoring of this repair, gelatine-collagen matrixes can easily incorporate bio-optical sensors for the simultaneous monitoring of inflammation processes and wound healing in time.

Acid-Induced Gelation of Carboxymethylcellulose Solutions.

The present work offers a comprehensive description of the acid-induced gelation of carboxymethylcellulose (CMC), a water-soluble derivative of cellulose broadly used in numerous applications ranging from food packaging to biomedical engineering. Linear viscoelastic properties measured at various pH and CMC contents allow us to build a sol-gel phase diagram and show that CMC gels exhibit broad power-law viscoelastic spectra that can be rescaled onto a master curve following a time-composition superposition principle. These results demonstrate the microstructural self-similarity of CMC gels and inspire a mean-field model based on hydrophobic interchain association that accounts for the sol-gel boundary over the entire range of CMC content under study. Neutron scattering experiments further confirm this picture and suggest that CMC gels comprise a fibrous network cross-linked by aggregates. Finally, low-field NMR measurements offer an original signature of acid-induced gelation from a solvent perspective. Altogether, these results open avenues for the precise manipulation and control of CMC-based hydrogels.