One‐Step Formation of Protein‐Based Tubular Structures for Functional Devices and Tissues

Abstract

Tubular biological structures consisting of extracellular matrix (ECM) proteins and cells are basic functional units of all organs in animals and humans. ECM protein solutions at low concentrations (5-10 milligrams per milliliter) are abundantly used in 3D cell culture. However, their poor "printability" and minute-long gelation time have made the direct extrusion of tubular structures in bioprinting applications challenging. Here, this limitation is overcome and the continuous, template-free conversion of low-concentration collagen, elastin, and fibrinogen solutions into tubular structures of tailored size and radial, circumferential and axial organization is demonstrated. The approach is enabled by a microfabricated printhead for the consistent circumferential distribution of ECM protein solutions and lends itself to scalable manufacture. The attached confinement accommodates minute-long residence times for pH, temperature, light, ionic and enzymatic gelation. Chip hosted ECM tubular structures are amenable to perfusion with aqueous solutions and air, and cyclic stretching. Predictive collapse and reopening in a crossed-tube configuration promote all-ECM valves and pumps. Tissue level function is demonstrated by factors secreted from cells embedded within the tube wall, as well as endothelial or epithelial barriers lining the lumen. The described approaches are anticipated to find applications in ECM-based organ-on-chip and biohybrid structures, hydraulic actuators, and soft machines.

High Throughput Omnidirectional Printing of Tubular Microstructures from Elastomeric Polymers

“…Despite the development of biofabrication techniques in generating cell‐free tubular scaffolds or cell‐laden microtubes with hydrogels such as collagen, gelatin methacryloyl, and alginate, [ 14b,27 ] the lack of mechanical strength and elasticity from hydrogel‐based scaffolds often leads to deformation of the tissue constructs as a result of cellular remodeling, which hinders the applicability of hydrogels to supporting long term culture. Thus, we chose to use synthetic elastomeric polymers as the material to make our tubes since they can provide the mechanical integrity required as structural support for cells and in particular, PICO and POMaC also offer the flexibility of tunable elasticity that can be adjusted via modifying synthesis conditions to suit the needs of specific applications.…”

“…The incorporation of natural elastic materials, namely elastin, into hydrogel networks of natural polysaccharides can improve stability and elasticity of these hydrogels, such that they form tubular structures that can resist the collapse during cellular remodeling. [14] In addition, collagen hydrogels used in tissue culture systems have often had different characteristics in comparison to the collagen structures of native tissues and these hydrogels have generally weak mechanical properties without further covalent crosslinking. [15] Synthetic elastomeric polymers can maintain their structure during the remodeling process of dense tissues.…”

Chiral Inorganic Nanomaterials for Photo(electro)catalytic Conversion

“…The use of diverse chiral templates results in abundant chiral assembly structures. In addition to silica helix, organic chiral supramolecular assemblies offer a more diverse and mature set of chiral templates. , Recently, owing to the natural chirality, some biopolymers and their derivatives have attracted much attention as chiral templates, such as cellulose nanocrystals (CNCs) for chiral liquid crystal superstructures, , proteins with different sequences and lengths for tubular and helical superstructures, , and helical DNA chains assembly or DNA origami templates for metal chiral pyramids or helices. , So far, Au NPs are commonly used as building blocks for chiral template-assisted assembly. There are two main methods to induce chiral configurations in achiral inorganic NPs via chiral templates.…”

Collagen Tubular Airway-on-Chip for Extended Epithelial Culture and Investigation of Ventilation Dynamics

“…Here, we report an advanced airway-on-a-chip model to overcome these limitations. Utilizing the previously reported extrusion of collagen-based tubular structures, [36] we present: ( 1…”

“…Here, we report an advanced airway-on-a-chip model to overcome these limitations. Utilizing the previously reported extrusion of collagen-based tubular structures, [36] we present: (1) A collagen tube based airway model for the human bronchial and alveolar ducts embedded with a custom designed microfluidic device; (2) The capacity of tuning the compliance and elasticity of the airway model wall within physiologically relevant ranges by tailoring collagen source and incubation protocol; (3) Confluent human bronchial epithelia lining the lumen of the tubular airway model, which developed and maintained under physiological air flow for up to 14 days; (4) Three ALI conditions: static, unidirectional, and bidirectional airflow, allow the investigation of airway dynamics during mechanical ventilation including shear stress, transmural pressure, tidal volume, cyclic stretch, effect of surfactant, expiratory flow resistance, as well as repetitive collapse and reopening; (5) The unique collapsible, stretchable and biocompatible nature of our tubular airway model allows combined studies of ventilation dynamics and resulting tissue injury.…”