Development of a hyaluronic acid-collagen bioink for shear-induced fibers and cells alignment.

Human tissues are characterized by complex composition and cellular and extracellular matrix (ECM) organization at microscopic level. In most of human tissues, cells and ECM show an anisotropic arrangement, which confers them specific properties.In vitro, the ability to closely mimic this complexity is limited. However, in the last years, extrusion bioprinting showed a certain potential for aligning cells and biomolecules, due to the application of shear stress during the bio-fabrication process. In this work, we propose a strategy to combine collagen (col) with tyramine-modified hyaluronic acid (THA) to obtain a printable col-THA bioink for extrusion bioprinting, solely-based on natural-derived components. Collagen fibers formation within the hybrid hydrogel, as well as collagen distribution and spatial organization before and after printing, were studied. For the validation of the biological outcome, fibroblasts were selected as cellular model and embedded in the col-THA matrix. Cell metabolic activity and cell viability, as well as cell distribution and alignment, were studied in the bioink before and after bioprinting. Results demonstrated successful collagen fibers formation within the bioink, as well as collagen anisotropic alignment along the printing direction. Furthermore, results revealed suitable biological properties, with a slightly reduced metabolic activity at day 1, fully recovered within the first 3 d post-cell embedding. Finally, results showed fibroblasts elongation and alignment along the bioprinting direction. Altogether, results validated the potential to obtain collagen-based bioprinted constructs, with both cellular and ECM anisotropy, without detrimental effects of the fabrication process on the biological outcome. This bioink can be potentially used for a wide range of applications in tissue engineering and regenerative medicine in which anisotropy is required.

Tubular Bioartificial Organs: From Physiological Requirements to Fabrication Processes and Resulting Properties. A Critical Review.

In this featured review manuscript, the aim is to present a critical survey on the processes available for fabricating bioartificial organs (BAOs). The focus will be on hollow tubular organs for the transport of anabolites and catabolites, i.e., vessels, trachea, esophagus, ureter and urethra, and intestine. First, the anatomic hierarchical structures of tubular organs, as well as their principal physiological functions, will be presented, as this constitutes the mandatory requirements for effectively designing and developing physiologically relevant BAOs. Second, 3D bioprinting, solution electrospinning, and melt electrowriting will be introduced, together with their capacity to match the requirements imposed by designing scaffolds compatible with the anatomical and physiologically relevant environment. Finally, the intrinsic correlation between processes, materials, and cells will be critically discussed, and directives defining the strengths, weaknesses, and opportunities offered by each process will be proposed for assisting bioengineers in the selection of the appropriate process for the target BAO and its specific required functions.

Elastin-like recombinamers in collagen-based tubular gels improve cell-mediated remodeling and viscoelastic properties.

Natural polymers are commonly used as scaffolds for vascular tissue engineering. The recognized biological properties of this class of materials are often counterbalanced by their low mechanical performance. In this work, recombinant elastin-like polypeptides (or elastin-like recombinamers, ELRs) were mixed with collagen gel and cells to produce cellularized tubular constructs in an attempt to recapitulate the mechanical behavior of the vascular extracellular matrix (ECM). The presence of the elastic protein influenced cell-mediated remodeling evaluated in terms of construct compaction, cell proliferation and ECM (collagen, elastin and fibrillin-1) gene expression. The partial substitution of collagen with ELR and the observed differences in cellular behavior synergistically contributed to the superior viscoelastic properties of the constructs containing 30% ELR and 70% of collagen (in mass). This led to the improvement of 40% in the initial elastic modulus, 50% in the equilibrium elastic modulus, and 37% in the tensile strength at break without compromising the strain at break, when compared to a pure collagen scaffold. Suggestions for future research include modifications in the crosslinking technology, ELR composition, polymer concentration, cell seeding density and dynamic stimulation, which have the potential to further improve the mechanical performance of the constructs towards physiological values.