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

Abstract

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.

Flax fibre reinforced alginate poloxamer hydrogel: assessment of mechanical and 4D printing potential

“… 5 Natural hydrogels based on alginate are one of the most widespread biomaterial used in tissue engineering. 6 However, alginate-based solutions are complex to print due to their low viscosity. 6 Hence, alginate can be combined with the surfactant poloxamer, for instance, as wound dressing materials 7 or for 3D bioprinting.…”

“… 6 However, alginate-based solutions are complex to print due to their low viscosity. 6 Hence, alginate can be combined with the surfactant poloxamer, for instance, as wound dressing materials 7 or for 3D bioprinting. 8 However, the range of accessible mechanical properties in hydrogels is somewhat limited, and precludes their more widespread adoption in materials science.…”

The influence of viscosity of hydrogels on the spreading and migration of cells in 3D bioprinted skin cancer models

“…Bioinks are bioprintable materials that are based on natural and synthetic polymers ( Parak et al, 2019 ) and are defined as cell-containing formulations that can be processed by biofabrication technology ( Van Kampen et al, 2019 ). Biopolymers are used as the bioink during the printing process which has the necessary characteristics, including biocompatibility, biodegradability, good degradation kinetics, and safe degradation by-products and they can enhance cell migration and adhesion (or tissue biomimicry) ( Cojocaru et al, 2019 ; Patrocinio et al, 2023 ). Hydrogels are often used as the basis of bioinks because of their ability to retain large amounts of water and form 3D structures ( Figure 4 ).…”