Tissue Engineering Cartilage with Deep Zone Cytoarchitecture by High‐Resolution Acoustic Cell Patterning

Abstract

The ultimate objective of tissue engineering is to fabricate artificial living constructs with a structural organization and function that faithfully resembles their native tissue counterparts. For example, the deep zone of articular cartilage possesses a distinctive anisotropic architecture with chondrocytes organized in aligned arrays ≈1-2 cells wide, features that are oriented parallel to surrounding extracellular matrix fibers and orthogonal to the underlying subchondral bone. Although there are major advances in fabricating custom tissue architectures, it remains a significant technical challenge to precisely recreate such fine cellular features in vitro. Here, it is shown that ultrasound standing waves can be used to remotely organize living chondrocytes into high-resolution anisotropic arrays, distributed throughout the full volume of agarose hydrogels. It is demonstrated that this cytoarchitecture is maintained throughout a five-week course of in vitro tissue engineering, producing hyaline cartilage with cellular and extracellular matrix organization analogous to the deep zone of native articular cartilage. It is anticipated that this acoustic cell patterning method will provide unprecedented opportunities to interrogate in vitro the contribution of chondrocyte organization to the development of aligned extracellular matrix fibers, and ultimately, the design of new mechanically anisotropic tissue grafts for articular cartilage regeneration.

Development of a Nanohybrid Peptide Hydrogel for Enhanced Intervertebral Disc Repair and Regeneration

“…NHPH with hierarchal structures demonstrated biomimetic mechanical properties that mimic natural collagen ECM at the nanoscale as well as microscale, while providing 3D-printing macroscale capabilities over conventional polymeric hydrogel materials used for biomedical applications such as gelatin or alginate. Although hierarchical structures have been previously applied for modulation of regenerative cell behaviors, our NHPH is injectable, thus representing clear advantages over traditional approaches. − We further show that NHPHs have superior biophysical features due to nanomaterial-mediated accelerated drug release, tunable biodegradation, ROS scavenging, and MRI activity. However, due to the multifunctionality of NHPH, it is unclear which therapeutic function of NHPH is making the most significant contributions to the fibrocartilaginous tissue regeneration, necessitating future studies on its mechanism.…”

Rational Design and Acoustic Assembly of Human Cerebral Cortex‐Like Microtissues from hiPSC‐Derived Neural Progenitors and Neurons

“…[ 24 ] Bulk acoustic waves have been used to generate stripe, ring, cluster shaped tissue architectures and further applied to fabricate muscle, [ 25 ] cortex, [ 17 ] and cartilage tissues. [ 26 ] Notably, bulk acoustic waves have been demonstrated to construct concentric cytoarchitectures by patterning DRG neurons and PC12 cells. [ 27 ] However, these patterned neural cells did not exhibit any physiological functions.…”

Hypotrochoidal scaffolds for cartilage regeneration

“…The cells that attach to the fibers of the scaffold could start secreting pro-collagen and assemble it into collagen fibrils following the hypotrochoidal pattern. Other techniques such as single cell acoustic patterning already allow cells to be arranged in a way that mimics the deep zone of cartilage [54]. The combination of cell patterning and having a template for the cells to follow could be worth exploring.…”