Yifei Jin

Self-Supporting Nanoclay as Internal Scaffold Material for Direct Printing of Soft Hydrogel Composite Structures in Air

Three dimensional (3D) bioprinting technology enables the freeform fabrication of complex constructs from various hydrogels and is receiving increasing attention in tissue engineering. The objective of this study is to develop a novel self-supporting direct hydrogel printing approach to extrude complex 3D hydrogel composite structures in air without the help of a support bath. Laponite, a member of the smectite mineral family, is investigated to serve as an internal scaffold material for the direct printing of hydrogel composite structures in air. In the proposed printing approach, due to its yield-stress property, Laponite nanoclay can be easily extruded through a nozzle as a liquid and self-supported after extrusion as a solid. Its unique crystal structure with positive and negative charges enables it to be mixed with many chemically and physically cross-linked hydrogels, which makes it an ideal internal scaffold material for the fabrication of various hydrogel structures. By mixing Laponite nanoclay with various hydrogel precursors, the hydrogel composites retain their self-supporting capacity and can be printed into 3D structures directly in air and retain their shapes before cross-linking. Then, the whole structures are solidified in situ by applying suitable cross-linking stimuli. The addition of Laponite nanoclay can effectively improve the mechanical and biological properties of hydrogel composites. Specifically, the addition of Laponite nanoclay results in a significant increase in the Youngs modulus of each hydrogel-Laponite composite: 1.9-fold increase for the poly(ethylene glycol) diacrylate (PEGDA)-Laponite composite, 7.4-fold increase for the alginate-Laponite composite, and 3.3-fold increase for the gelatin-Laponite composite.

Printability study of hydrogel solution extrusion in nanoclay yield-stress bath during printing-then-gelation biofabrication

Yield-stress support bath-enabled extrusion printing is emerging as a promising filament-based direct-write strategy for different applications in tissue engineering and regenerative medicine. Central to the printing quality of complex three-dimensional structures fabricated by the support bath-enabled fabrication approach is the formation of a continuous filament with well-defined geometry. The objective of this research is to study the printability of hydrogel precursor solutions in a Laponite nanoclay yield-stress bath during extrusion printing where the printed hydrogel precursor solutions remain liquid. The printability herein is mainly evaluated based on the morphology and dimensions of printed liquid filaments. Seven filament types are observed during extrusion in the nanoclay bath: three types of well-defined filaments (swelling, equivalent diameter, and stretched) and four types of irregular filaments (rough surface, over-deposited, compressed, and discontinuous). When the alginate concentration increases, the diameter of filaments made of alginate-gelatin blends decreases. The nanoclay concentration significantly affects the morphology of deposited filaments: low concentration Laponite bath (such as 0.5% (w/v)) may lead to the formation of irregular filaments such as rough surface and over-deposited filaments while high concentration bath (such as 8.0% (w/v)) may result in the formation of compressed filaments. Operating conditions affect the filament diameter and morphology similar to those as observed during conventional extrusion printing. The printability knowledge enables the successful fabrication of cellular vascular constructs in the Laponite nanoclay bath.

Effects of printing-induced interfaces on localized strain within 3D printed hydrogel structures

Additive manufacturing, or 3D printing, is a promising approach for the fabrication of biological structures for regenerative medicine applications using tissue-like materials such as hydrogels. Herein, inkjet printing is implemented as a model droplet-based 3D printing technology for which interfaces have been shown to form between printed lines within printed layers of hydrogel structures. Experimental samples with interfaces in two orientations are fabricated by inkjet printing and control samples with and without interfaces are fabricated by extrusion printing and casting, respectively. The formation of partial and full interfaces is modeled in terms of printing conditions and gelation parameters, and an approach to predicting the ratio of interfacial area to the total contact area between two adjacent lines is presented. Digital image correlation is used to determine strain distributions and identify regions of increased localized deformation for samples under uniaxial tension. Despite the presence of interfaces in inkjet-printed samples, strain distributions are found to be homogeneous regardless of interface orientation, which may be attributed to the multi-layer nature of samples. Conversely, single-layer extrusion-printed samples exhibit localized regions of increased deformation between printed lines, indicating delamination along interfaces. The effective stiffness, failure strength, and failure strain of inkjet-printed samples are found to be dependent on the orientation of interfaces within layers. Specifically, inkjet-printed samples in which tensile forces pull apart interfaces exhibit significantly decreased mechanical properties compared to cast samples.

Nanoclay-Based Self-Supporting Responsive Nanocomposite Hydrogels for Printing Applications.

Stimuli-responsive hydrogels and/or composite hydrogels have been of great interest for various printing applications including four-dimensional printing. Although various responsive hydrogels and/or composite hydrogels have been found to respond to given stimuli and change shapes as designed, the fabrication of three-dimensional (3D) structures from such responsive hydrogels is still a challenge due to their poor 3D printability, and most of the responsive material-based patterns are two-dimensional (2D) in nature. In this study, Laponite nanoclay is studied as an effective additive to improve the self-supporting printability of N-isopropylacrylamide (NIPAAm), a thermoresponsive hydrogel precursor while keeping the responsive functionality of NIPAAm. Graphene oxide (GO) is further added as a nanoscale heater, responding to near-infrared radiation. Due to the different shrinking ratios and mechanical properties of the poly( N-isopropylacrylamide) (pNIPAAm)-Laponite and pNIPAAm-Laponite-GO nanocomposite hydrogels, printed 2D patterns deform in a predictable way. In addition, 3D microfluidic valves are directly printed and cured in air, which can effectively control the flow directions in response to different stimuli as validated in a microfluidic system. Because Laponite nanoclay can be mixed with various responsive hydrogel precursors to improve their 3D printability, the proposed Laponite nanoclay-based nanocomposite hydrogels can be further expanded to prepare various 3D printable responsive nanocomposite hydrogels.

Fabrication of Stand-Alone Cell-Laden Collagen Vascular Network Scaffolds Using Fugitive Pattern-Based Printing-Then-Casting Approach

Vascular networks are of great significance in tissue engineering and viewed as the first step to fabricate human tissues. Although various techniques have been investigated to create vascular and vascular-like networks, the fabrication of stand-alone pure collagen-based vascular constructs is still a challenge because of the poor extrudability, weak mechanical property, and long cross-linking time of pure collagen solutions. In this study, a fugitive pattern-based printing-then-casting approach is investigated. The proposed alginate-based fugitive ink has excellent mechanical strength (by adding Laponite nanoclay), printability (by adding Laponite nanoclay), and controllable gelation rate (by adding disodium hydrogen phosphate). Using this fugitive ink, complex vascular-like structures can be easily printed and cross-linked in Laponite EP bath as fugitive vascular tree patterns. Each fugitive vascular tree pattern is then embedded in a gelatin bath to make a gelatin mold with the tree patterns. With the help of sodium citrate, the fugitive vascular tree pattern is liquefied and removed to create the gelatin mold with vascular channels. Finally, a stand-alone collagen vascular network scaffold embedded with fibroblasts can be fabricated by casting the cell-laden collagen suspension into the gelatin mold and releasing it from the mold at 37 °C. The cell-related investigations indicate that the cells grow and spread well in the pure collagen vascular network scaffold. The proposed hybrid printing-then-casting approach also provides a feasible technology to fabricate with materials having low viscosity, long gelation time, and poor mechanical property.

Fabrication of Double-Layered Alginate Capsules Using Coaxial Nozzle

Multilayered encapsulation has been of great interest for various pharmaceutical, chemical, and food industries. Fabrication of well-defined capsules with more than one shell layer still poses a significant fabrication challenge. This study aims to investigate the feasibility of using a coaxial nozzle to fabricate double-layered (core–shell–shell) capsules during vibration-assisted dripping. A three-layered coaxial nozzle has been designed, manufactured, and tested for double-layered capsule fabrication when using sodium alginate solutions as the model liquid material for inner and outer shell layers and calcium chloride solution as the core fluid. To facilitate the droplet formation process, a vibrator has been integrated into the fabrication system to provide necessary perturbation for effective breakup of the fluid flow. It is demonstrated that double-layered alginate capsules can be successfully fabricated using the proposed three-layered coaxial nozzle fabrication system. During fabrication, increasing the core flow rate leads to an increase in capsule and core diameters while the inner and outer shell layer thicknesses decrease. Increasing annular flow rate results in an increase in capsule diameter and inner shell layer thickness while the outer shell layer thickness decreases. An increase in the sheath flow rate leads to an increase in capsule diameter and outer shell layer thickness but has no significant effect on the core diameter and inner shell layer thickness. [DOI: 10.1115/1.4037646]