Leachable‐Free Fabrication of Hydrogel Foams Enabling Homogeneous Viability of Encapsulated Cells in Large‐Volume Constructs

Abstract

The popularity of cell-laden injectable hydrogels has steeply increased due to their compatibility with minimally invasive surgical procedures. However, the diffusion of indispensable molecules for cell survival through bulk hydrogel structures, particularly oxygen, is often limited to micrometric distances, often hampering cell viability or uniform tissue formation in constructs with clinically relevant sizes. The introduction of micropores in hydrogels or the use of oxygen-generating materials has enabled combining advantages of porous 3D scaffolds with the injectability properties of in situ-solidifying hydrogels. Here, cell-laden injectable gelatin methacryloyl (GelMA) foams are fabricated using a single polymer formulation. Air bubbles are introduced into GelMA solutions using a simple-to-implement method based on pulling/pushing the solution through a syringe. Human mesenchymal stem cells derived from the adipose tissue (hASCs) cultured in bulk hydrogels (diameter c.a. 5 mm) show low permanence in the core of the materials and stain for factors associated to hypoxia (hypoxia-inducible factor-1 alpha (HIF-1)) after 7 days of culture. In opposition, cells cultured in optimized foams do not stain for HIF-1 , show high permanence, homogeneous viability, and consistent phenotype in the whole depth of the biomaterials, while secreting increased amounts of regenerative growth factors to the surrounding medium.

Architecting polyelectrolyte hydrogels with Cu-assisted polydopamine nanoparticles for photothermal antibacterial therapy

“…Next, the hydrogels were taken out of the PBS and weighed (W t ) at certain intervals after removing the PBS on the hydrogel surface. Finally, the water uptake was calculated employing the following formula [ 29 ]: Water uptake = (W t – W d )/W d Where W t is the mass of the swollen hydrogel specimen and W d is the mass of the initial hydrogel specimen.…”

Colloidal multiscale porous adhesive (bio)inks facilitate scaffold integration

“…Although the formed bubbles enhance cell viability in the core of the hydrogel, there was no control over the bubble (pore) sizes and distribution. 35 In this study, inspired by whipped cream production, we developed porous bioinks through a single step foaming process without using any toxic material. To form porous bioinks, the prepolymer solution was mechanically agitated by simple stirring, at relatively high rates, to generate a foam with a uniform, interconnected pore structure and porosity up to 80%.…”

Minimalist Tissue Engineering Approaches Using Low Material‐Based Bioengineered Systems

“…Strategies to incorporate oxygen microbubbles include the straightforward foaming of methacrylated gelatin, which can then be UV crosslinked, and laden with cells. [ 129 ] Hydrogel bead‐based scaffolds are another alternative for the development of porous macrostructures due to the intrinsic porosity formed between microbeads upon chemical bonding. An example is the application of a 4‐arm polyethyleneglycol (PEG)‐ N ‐hydroxysuccinimide crosslinker for a spontaneous adhesion of cell‐laden, norbornene‐functionalized gelatin microbeads into a robust, porous structure (Figure 5D1).…”