Microfluidic Flow Cell Array for Controlled Cell Deposition in Engineered Musculoskeletal Tissues

Abstract

Musculoskeletal tissues contain critical gradients in extracellular matrix (ECM) composition and cell types that allow for proper mechanical function of tissues and integration between adjacent tissues. However, properly controlling these patterns in engineered tissues is difficult and tissue engineering (TE) is presently in need of methods to generate integration zones for tissue anchoring, transition zones between tissues, and controlled ECM gradients for proper mechanical function. In this study, we present a novel method of using a microfluidic flow cell array (MFCA) to precisely control cell deposition onto TE constructs to produce tunable cell patterns on engineered constructs. In this study, we characterized MFCA cell deposition to efficiently and reliably deposit cells in controllable patterns and densities. We developed methods for deposition of human adipose-derived stem cells and human osteoblasts using a 12-channel pilot printhead. We mimicked key gradients and transitions by creating two-cell and three-cell-type transitions characteristic of the integration zones of musculoskeletal tissues. Overall, we demonstrate the ability to precisely and reproducibly control cell deposition on engineered constructs using this method and control cell population gradients. We establish the production of multicell transitions and multicell interfaces utilizing MFCA cell deposition, to demonstrate the potential of the method to create an extensive variety of engineered musculoskeletal tissues. Furthermore, customization of the printhead design can accommodate various structures, sizes, shapes, and number of flow cell channels to meet specific requirements for a broad range of musculoskeletal tissues.

Development of a 3D-Printed Drug-Eluting Stent for Treating Obstructive Salivary Gland Disease

“…This phenomenon may facilitate the loading of various antibiotics. In addition, unlike PLA and PLGA, PCL does not produce acidic byproducts during the biodegradation process, thereby causing less damage to the surrounding tissues. , So far, PCL has been used as a biomaterial for the reconstruction of various tissues such as bone, cartilage, liver, muscle, vessel, ligament, and trachea in regenerative medicine. − When AMOX or CTX was mixed with PCL and stents were fabricated by 3D printing system, tensile and yield strength were increased by included drugs as a composite material. Although an elongation of the drug-eluting stent was reduced compared to the drug-free stent, because it was increased by more than 50% from the initial structure, so it will be able to maintain the structure through an expansion of the lumen in a situation of the increased saliva flow.…”

Review of Low-Cost 3D Bioprinters: State of the Market and Observed Future Trends

“…Recently, the advancement of microfluidic plumbing technologies has increasingly led to their use in synthesizing biomaterials, 216 printing high-throughput assays, 217 and seeding cells in engineered tissues. 218 Likewise, microfluidic print heads have demonstrated great potential in replacing the traditional extrusion-based and droplet-based technologies due to numerous advantages, such as fast continuous switching and mixing of materials, high-resolution bio-ink deposition, and reducing the shear stresses experienced by the extruded cells (see the "High-End Microfluidics-Based Printers" section for more details). 219,220 These new capabilities can potentially revolutionize the 3D fabrication of artificial tissues by enabling the generation of highly organized and patterned microenvironments and organoids using multicell/multimaterial bio-inks.…”

Three‐dimensional printing: The potential technology widely used in medical fields

“…The skeletal muscle system has a key gradient in the composition and cell type of extracellular matrix, which is reflected in some transition areas, such as the calcified and noncalcified areas of ligaments, and the cartilaginous vertebral endplate of the intervertebral disc. Ede et al used a special print head with a microfluidic device to generate a complex tendon, ligament and intervertebral disc in vitro (Ede, Davidoff, Blitch, Farhang, & Bowles, 2018). The print head can lay fat stem cells as needed to precisely deposit the cells and produce a steady gradient of cells.…”