Biopolymers for Tissue Engineering: Crosslinking, Printing Techniques, and Applications.

Currently, tissue engineering has been dedicated to the development of 3D structures through bioprinting techniques that aim to obtain personalized, dynamic, and complex hydrogel 3D structures. Among the different materials used for the fabrication of such structures, proteins and polysaccharides are the main biological compounds (biopolymers) selected for the bioink formulation. These biomaterials obtained from natural sources are commonly compatible with tissues and cells (biocompatibility), friendly with biological digestion processes (biodegradability), and provide specific macromolecular structural and mechanical properties (biomimicry). However, the rheological behaviors of these natural-based bioinks constitute the main challenge of the cell-laden printing process (bioprinting). For this reason, bioprinting usually requires chemical modifications and/or inter-macromolecular crosslinking. In this sense, a comprehensive analysis describing these biopolymers (natural proteins and polysaccharides)-based bioinks, their modifications, and their stimuli-responsive nature is performed. This manuscript is organized into three sections: (1) tissue engineering application, (2) crosslinking, and (3) bioprinting techniques, analyzing the current challenges and strengths of biopolymers in bioprinting. In conclusion, all hydrogels try to resemble extracellular matrix properties for bioprinted structures while maintaining good printability and stability during the printing process.

Three-Dimensionally Printed Hydrogel Cardiac Patch for Infarct Regeneration Based on Natural Polysaccharides.

Myocardial infarction is one of the more common cardiovascular diseases, and remains the leading cause of death, globally. Hydrogels (namely, those using natural polymers) provide a reliable tool for regenerative medicine and have become a promising option for cardiac tissue regeneration due to their hydrophilic character and their structural similarity to the extracellular matrix. Herein, a functional ink based on the natural polysaccharides Gellan gum and Konjac glucomannan has, for the first time, been applied in the production of a 3D printed hydrogel with therapeutic potential, with the goal of being locally implanted in the infarcted area of the heart. Overall, results revealed the excellent printability of the bioink for the development of a stable, porous, biocompatible, and bioactive 3D hydrogel, combining the specific advantages of Gellan gum and Konjac glucomannan with proper mechanical properties, which supports the simplification of the implantation process. In addition, the structure have positive effects on endothelial cells' proliferation and migration that can promote the repair of injured cardiac tissue. The results presented will pave the way for simple, low-cost, and efficient cardiac tissue regeneration using a 3D printed hydrogel cardiac patch with potential for clinical application for myocardial infarction treatment in the near future.

Improving Cell Viability and Velocity in µ-Extrusion Bioprinting with a Novel Pre-Incubator Bioprinter and a Standard FDM 3D Printing Nozzle.

Bioprinting is a promising emerging technology. It has been widely studied by the scientific community for the possibility to create transplantable artificial tissues, with minimal risk to the patient. Although the biomaterials and cells to be used are being carefully studied, there is still a long way to go before a bioprinter can easily and quickly produce printings without harmful effects on the cells. In this sense, we have developed a new µ-extrusion bioprinter formed by an Atom Proton 3D printer, an atmospheric enclosure and a new extrusion-head capable to increment usual printing velocity. Hence, this work has two main objectives. First, to experimentally study the accuracy and precision. Secondly, to study the influence of flow rates on cellular viability using this novel µ-extrusion bioprinter in combination with a standard FDM 3D printing nozzle. Our results show an X, Y and Z axis movement accuracy under 17 µm with a precision around 12 µm while the extruder values are under 5 and 7 µm, respectively. Additionally, the cell viability obtained from different volumetric flow tests varies from 70 to 90%. So, the proposed bioprinter and nozzle can control the atmospheric conditions and increase the volumetric flow speeding up the bioprinting process without compromising the cell viability.

Nanopatterned polystyrene-b-poly(acrylic acid) surfaces to modulate cell-material interaction.

In this work we explore the effect of surface nanoarchitecture of polystyrene (PS) and polystyrene-b-poly(acrylic acid) (PS-b-PAA) diblock copolymer films on cell viability. PS and PS-b-PAA have been nanopatterned at temperatures of 110, 120 and 140°C using nanoporous aluminium oxide membranes (AAO) as a template. Surface architecture strongly depends on the infiltration temperature and the nature of the infiltrated polymer. High patterning temperatures yield hollow fibre shape architecture at the nanoscale level, which substantially modifies the surface hydrophobicity of the resulting materials. Up to date very scarce reports could be found in the literature dealing with the interaction of microstructured/nanostructured polymeric surfaces with cancer cells. Therefore, MCF-7 breast cancer cells have been selected as a model to conduct cell viability assays. The findings reveal that the fine-tuning of the surface nanoarchitecture contributes to the modification of its biocompatibility. Overall, this study highlights the potential of AAO membranes to obtain well-defined tailored morphologies at nanoscale level and its importance to develop novel soft functional surfaces to be used in the biomedical field.