Multiscale Anisotropic Tissue Biofabrication via Bulk Acoustic Patterning of Cells and Functional Additives in Hybrid Bioinks

Abstract

Recapitulation of the microstructural organization of cellular and extracellular components found in natural tissues is an important but challenging feat for tissue engineering, which demands innovation across both process and material fronts. In this work, a highly versatile ultrasound-assisted biofabrication (UAB) approach is demonstrated that utilizes radiation forces generated by superimposing ultrasonic bulk acoustic waves to rapidly organize arrays of cells and other biomaterial additives within single and multilayered hydrogel constructs. UAB is used in conjunction with a novel hybrid bioink system, comprising of cartilage-forming cells (human adipose-derived stem cells or chondrocytes) and additives to promote cell adhesion (collagen microaggregates or polycaprolactone microfibers) encapsulated within gelatin methacryloyl (GelMA) hydrogels, to fabricate cartilaginous tissue constructs featuring bulk anisotropy. The hybrid matrices fabricated under the appropriate synergistic thermo-reversible and photocrosslinking conditions demonstrate enhanced mechanical stiffness, stretchability, strength, construct shape fidelity and aligned encapsulated cell morphology and collagen II secretion in long-term culture. Hybridization of UAB is also shown with extrusion and stereolithography printing to fabricate constructs featuring 3D perfusable channels for vasculature combined with a crisscross or circumferential organization of cells and adhesive bioadditives, which is relevant for further translation of UAB toward complex physiological-scale biomimetic tissue fabrication. IntroductionCentral to the function of most tissues in the human body is the specific organization of the constitutive cells and extracellular

Instantly adhesive and ultra-elastic patches for dynamic organ and wound repair

“…The patch combination composition is simple enough to easily replicate and fabricate and can be linearly scaled-up for large-scale patch fabrication. Since the patches can be manufactured in a single layer, custom masks can also be used with UV lamps ( 70 ) to fabricate the patches, negating the need for complex projection systems in 3D printers and further reducing the cost of fabrication.…”

Macroporous Aligned Hydrogel Microstrands for 3D Cell Guidance

“…A no-slip condition was applied at the walls of the sizing grid. As for the meshing criteria, a free tetrahedral mesh with maximum element size of 2 μm (i.e., one-tenth the size of the minimum feature dimension of 20 μm), similar to in previous studies, was applied. , The compilation time for a parametric sweep across the three flow consistency indices was 18 min. The resulting shear stress was plotted across the entire width of an opening within the sizing grid.…”

Hydrogels to Recapture Extracellular Matrix Cues That Regulate Vascularization

“…Advanced 3D bioprinting techniques and acoustic cell assembly enabled the creation of microchannels and cellular architectures with various crosssections and different curvature angles (eg, straight, spiral, serpentine, curvilinear, and contraction-expansion), emulating the native, complex microvasculatures. [91][92][93] Techniques such as cavitation molding or multiphoton ablation have been used to generate cell-guiding channels in 3D collagen hydrogel, facilitating endothelialization and blood perfusion at anatomic capillary scale. 94,95 Dynamic flow patterns in 3D microfluidic hydrogel systems also play a prominent role in producing microvasculature in vitro with a length scale of up to 15 mm while maintaining high spatial resolution.…”