Three-dimensional (3D) bioprinting is on the cusp of permitting the direct fabrication of artificial living tissue. Multicellular building blocks (bioinks) are dispensed layer by layer and scaled for the target construct. However, only a few materials are able to fulfill the considerable requirements for suitable bioink formulation, a critical component of efficient 3D bioprinting. Alginate, a naturally occurring polysaccharide, is clearly the most commonly employed material in current bioinks. Here, we discuss the benefits and disadvantages of the use of alginate in 3D bioprinting by summarizing the most recent studies that used alginate for printing vascular tissue, bone and cartilage. In addition, other breakthroughs in the use of alginate in bioprinting are discussed, including strategies to improve its structural and degradation characteristics. In this review, we organize the available literature in order to inspire and accelerate novel alginate-based bioink formulations with enhanced properties for future applications in basic research, drug screening and regenerative medicine.

A model is developed that describes the sharp indentation behavior of time-dependent materials. The model constitutive equation is constructed from a series of quadratic mechanical elements, with independent viscous (dashpot), elastic (spring), and plastic (slider) responses. Solutions to this equation describe features observed under load-controlled indentation of polymers, including creep, negative unloading tangents, and loading-rate dependence. The model describes a full range of viscous–elastic–plastic responses and includes as bounding behaviors time-independent elastic–plastic indentation (appropriate to metals and ceramics) and time-dependent viscous–elastic indentation (appropriate to elastomers). Experimental indentation traces for a range of olymers with different material properties (elastic modulus, hardness, viscosity) are econvoluted and ranked by calculated time constant. Material properties for these polymers, deconvoluted from single load–unload cycles, are used to predict the indentation load–displacement behavior at loading rates three times slower and faster, as well as the steady-state creep rate under fixed load.

Tissue architecture is intimately linked with its functions, and loss of tissue organization is often associated with pathologies. The intricate depth-dependent extracellular matrix (ECM) arrangement in articular cartilage is critical to its biomechanical functions. In this study, we developed a Raman spectroscopic imaging approach to gain new insight into the depth-dependent arrangement of native and tissue-engineered articular cartilage using bovine tissues and cells. Our results revealed previously unreported tissue complexity into at least six zones above the tidemark based on a principal component analysis and k-means clustering analysis of the distribution and orientation of the main ECM components. Correlation of nanoindentation and Raman spectroscopic data suggested that the biomechanics across the tissue depth are influenced by ECM microstructure rather than composition. Further, Raman spectroscopy together with multivariate analysis revealed changes in the collagen, glycosaminoglycan, and water distributions in tissue-engineered constructs over time. These changes were assessed using simple metrics that promise to instruct efforts toward the regeneration of a broad range of tissues with native zonal complexity and functional performance.

Instrumented indentation is a widespread tool for characterising the mechanical properties of biological materials. Here, we show that the ratio between indentation hardness and modulus is approximately constant in biological materials. A simple elastic-plastic series deformation model is employed to rationalise part of this correlation, and criteria for a meaningful comparison of indentation hardness across biological materials are proposed. The ratio between indentation hardness and modulus emerges as the key parameter characterising the relative amount of irreversible deformation during indentation. Despite their comparatively high hardness to modulus ratio, biological materials are susceptible to quasiplastic deformation, due to their high toughness: quasi-plastic deformation is hence hypothesised to be a frequent yet poorly understood phenomenon, highlighting an important area of future research.

Depth-sensing indentation testing is a common way to characterize the mechanical behavior of stiff, time-independent materials but presents both experimental and analytical challenges for compliant, time-dependent materials. Many of these experimental challenges can be overcome by using a spherical indenter tip with a radius substantially larger than the indentation depth, thus restricting deformation to viscoelastic (and not plastic) modes in glassy polymers and permitting large loads and contact stiffness to be generated in compliant elastomers. Elastic-viscoelastic correspondence was used to generate spherical indenter solutions for a number of indentation testing protocols including creep following loading at a constant rate and a multiple ramp-and-hold protocol to measure creep response at several loads (and depths) within the same test. The ramp-creep solution was recast as a modification to a step-load creep solution with a finite loading rate correction factor that is a dimensionless function of the ratio of experimental ramp time to the material time constant. Creep tests were performed with different loading rates and different peak load levels on glassy and rubbery polymeric materials. Experimental data are fit to the spherical indentation solutions to obtain elastic modulus and time-constants, and good agreement is found between the results and known modulus values. Emphasis is given to the use of multiple experiments (or multiple levels within a single experiment) to test the a priori assumption of linear viscoelastic material behavior used in the modeling.