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Tolentino, M. K.

Publications and source records attributed to Tolentino, M. K..

2 recordsLinked to original sources

A 3D bioprintable hydrogel with tuneable stiffness for exploring cells encapsulated in matrices of differing stiffnesses

In vitro cell models have undergone a shift from 2D models on glass slides to 3D models that better reflect the native 3D microenvironment. 3D bioprinting promises to progress the field by allowing the high throughput production of reproducible cell-laden structures with high fidelity. As this technology is relatively new, the current stiffness range of printable matrices surrounding the cells that mimics the extracellular matrix environment remains limited. The work presented here aims to expand the range of stiffnesses by utilising a 4-armed polyethylene glycol with maleimide functionalised arms. The complementary crosslinkers comprised a matrix metalloprotease (MMP)-degradable peptide and a 4-armed thiolated polymer which were adjusted in ratio to tune the stiffness. The modularity of this system allows for a simple method of controlling stiffness and the addition of biological motifs. The application of this system in drop-on-demand printing is validated in this work using MCF-7 cells which were monitored for viability and proliferation. This study shows the potential of this system for the high-throughput investigation of the effects of stiffness and biological motif compositions in relation to cell behaviours.

cell biology↗

A high-throughput 3D bioprinted cancer cell migration and invasion model with versatile and broad biological applicability

Understanding the underlying mechanisms of migration and metastasis is a key focus of cancer research. There is an urgent need to develop in vitro 3D tumor models that can mimic physiological cell-cell and cell-extracellular matrix interactions, with high reproducibility and that are suitable for high throughput (HTP) drug screening. Here, we developed a HTP 3D bioprinted migration model using a bespoke drop-on-demand bioprinting platform. This HTP platform coupled with tunable hydrogel systems enables (i) the rapid encapsulation of cancer cells within in vivo tumor mimicking matrices, (ii) in situ and real-time measurement of cell movement, (iii) detailed molecular analysis for the study of mechanisms underlying cell migration and invasion, and (iv) the identification of novel therapeutic options. This work demonstrates that this HTP 3D bioprinted cell migration platform has broad applications across quantitative cell and cancer biology as well as drug screening.

cell biology↗