Human‐Recombinant‐Elastin‐Based Bioinks for 3D Bioprinting of Vascularized Soft Tissues

Abstract

Bioprinting has emerged as an advanced method for fabricating complex 3D tissues. Despite the tremendous potential of 3D bioprinting, there are several drawbacks of current bioinks and printing methodologies that limit the ability to print elastic and highly vascularized tissues. In particular, fabrication of complex biomimetic structure that are entirely based on 3D bioprinting is still challenging primarily due to the lack of suitable bioinks with high printability, biocompatibility, biomimicry, and proper mechanical properties. To address these shortcomings, in this work the use of recombinant human tropoelastin as a highly biocompatible and elastic bioink for 3D printing of complex soft tissues is demonstrated. As proof of the concept, vascularized cardiac constructs are bioprinted and their functions are assessed in vitro and in vivo. The printed constructs demonstrate endothelium barrier function and spontaneous beating of cardiac muscle cells, which are important functions of cardiac tissue in vivo. Furthermore, the printed construct elicits minimal inflammatory responses, and is shown to be efficiently biodegraded in vivo when implanted subcutaneously in rats. Taken together, these results demonstrate the potential of the elastic bioink for printing 3D functional cardiac tissues, which can eventually be used for cardiac tissue replacement.

Current Insight of Printability Quality Improvement Strategies in Natural-Based Bioinks for Skin Regeneration and Wound Healing

“…High mechanical force or pressure needs to be applied to push the high viscosity hydrogel out from the nozzle. A previous study on the shear-thinning properties of gelatin-elastin bioinks by using extrusion-based bioprinting indicated that the level of shear stress increases when the pressure in the extrusion piston increases [ 72 ]. Figure 5 a shows the shear stress region in the syringe during the printing procedure.…”

“…However, the shape fidelity of the hydrogel can be improved by printing a complex structure of the hydrogels [ 72 ]. The main concept of 3D-bioprinting is to print the hydrogel layer-by-layer until it forms a composite scaffold.…”

“…Gelatin is known as a natural-based bioink that has a reverse effect on gelation or polymerisation properties. The gelatin’s viscosity is usually incorporated with temperature during printing [ 72 ]. Therefore, to overcome the limitation of the gelatin’s low viscosity, the concentration of the gelatin needs to be increased and in use in combination with other natural bioinks such as alginate or with an additional crosslinker to allow high printing fidelity [ 73 , 74 , 75 ].…”

Natural-Based Hydrogels for Tissue Engineering Applications

“…The blending of MeTro with other polymers has been explored to enhance their elasticity. For instance, it was blended with GelMA to obtain elastic bioinks that were used for 3D printing of vascularized cardiac constructs that showed endothelium barrier function and spontaneous beating of cardiac muscle cells [ 36 ].…”

Thixotropic Hydrogels Composed of Self-Assembled Nanofibers of Double-Hydrophobic Elastin-Like Block Polypeptides

“…Chemically crosslinked, cell-compatible elastin-like hydrogels have been constructed carefully designing the crosslinking reactions. Weiss et al synthesized methacrylate derivative of tropoelastin, the monomeric form of elastin [ 8 , 9 ]. This derivative is photo-crosslinked to form hydrogels within a minute upon ultraviolet (UV) irradiation.…”