Evaluating alternative crosslinking agents in poly(vinyl alcohol) hydrogels membranes

Hydrogels are a network of polymer chains with properties that absorb, store and transport solutions. A hydrogel membrane has a permeability that allows influx and excretion. Therefore, it is the ideal material for medicated membranes. This study investigates the crosslinking of poly(vinyl alcohol) (PVA) hydrogel membranes using different agents and explores the usability of the candidate membranes as drug delivery systems. The model protein, bovine albumin serum (BSA), was used to test the stability and controlled drug release rate characteristics of the candidate hydrogel membranes. This investigation also evaluated the stability different crosslinkers for hydrogel membranes. Glutaraldehyde (GA) and an alternative crosslinking method of ultraviolet irradiation with the sensitizer, sodium benzoate (SB), were used to crosslink PVA containing BSA. In GA crosslinked membranes, BSA release diffusion experiments showed 48%, 45%, and 63% recovery of protein at pH 6.5, 7.4 and 8.0, respectively; this confirmed that this system is suited for physiological conditions and controlled release. Although SB has been used for membrane fabrication, our Fourier Transform Infrared Spectroscopy (FTIR) and Thermogravimetric Analysis (TGA) results indicate that UV(SB)-crosslinked films are not suited for drug delivery, despite the release of BSA

Inkjet-printed morphogenesis of tumor-stroma interface using bi-cellular bioinks of collagen-poly(N-isopropyl acrylamide-co-methyl methacrylate) mixture

Recent advances in biomaterials and 3D printing/culture methods enable various tissue-engineered tumor models. However, it is still challenging to achieve native tumor-like characteristics due to lower cell density than native tissues and prolonged culture duration for maturation. Here, we report a new method to create tumoroids with a mechanically active tumor-stroma interface at extremely high cell density. This method, named “inkjet-printed morphogenesis” (iPM) of the tumor-stroma interface, is based on a hypothesis that cellular contractile force can significantly remodel the cell-laden polymer matrix to form densely-packed tissue-like constructs. Thus, differential cell-derived compaction of tumor cells and cancer-associated fibroblasts (CAFs) can be used to build a mechanically active tumor-stroma interface. In this methods, two kinds of bioinks are prepared, in which tumor cells and CAFs are suspended respectively in the mixture of collagen and poly (N-isopropyl acrylamide-co-methyl methacrylate) solution. These two cellular inks are inkjet-printed in multi-line or multi-layer patterns. As a result of cell-derived compaction, the resulting structure forms tumoroids with mechanically active tumor-stroma interface at extremely high cell density. We further test our working hypothesis that the morphogenesis can be controlled by manipulating the force balance between cellular contractile force and matrix stiffness. Furthermore, this new concept of “morphogenetic printing” is demonstrated to create more complex structures beyond current 3D bioprinting techniques