Biology subjects

Tam, T.

Publications and source records attributed to Tam, T..

3 recordsLinked to original sources

bioRxiv2024

Programmable 3D cell alignment of bioprinted tissue via soft robotic dynamic stimulation

Recent breakthroughs in biofabrication have enabled the development of engineered tissues for various organ systems, supporting applications in drug testing and regenerative medicine. However, current approaches do not allow for dynamic mechanical maturation of engineered tissue in 3D. Although uniaxial mechanostimulation techniques have shown promise in generating anisotropic tissues, they fail to recapitulate the biomechanics of complex tissues. As a result, existing biofabricated tissues lack the ability to replicate complex 3D alignment patterns essential for functional biomimicry. Here, we present a soft robotics-driven approach for programmable 3D alignment in 3D bioprinted tissue. Our method introduces the co-printing of biological tissue with a silicone-based soft robot via a custom core-double shell nozzle. The application of 3D, exogenous, dynamic expansion and torsional forces to the tissue via the co-printed silicone robot was found to drive cell alignment. Confocal imaging revealed pronounced anisotropy of the stimulated tissue samples compared to the unstimulated controls. In addition, different cellular orientation patterns resulted from each mode of stimulation, demonstrating the versatility of the soft robotic approach in tailoring the pattern of tissue alignment based on programmed mechanostimulation.

bioengineering↗

bioRxiv2024

A low-cost, open-source 3D printer for multimaterial and high-throughput direct ink writing of soft and living materials

Direct ink writing is a 3D printing method that is compatible with a wide range of structural, elastomeric, electronic, and living materials, and it continues to expand its uses into physics, engineering, and biology laboratories. However, the large footprint, closed hardware and software ecosystems, and expense of commercial systems often hamper widespread adoption. Here, we present a compact, simple-to-build, low-cost, multimaterial, and high-throughput direct ink writing 3D printer platform with detailed assembly files and instructions provided freely online. In contrast to existing low-cost 3D printers and bioprinters, which typically modify off-the-shelf plastic 3D printers, this system is built from scratch, offering a lower cost and full customizability. Despite its low cost, we demonstrate advanced active mixing and multimaterial multinozzle 3D (MM3D) printing methods, which previously have relied on expensive and custom motion control platforms. We finally introduce embedded multinozzle and 3D gradient nozzle designs that offer high throughput and graded 3D parts. This powerful, easy-to-build, and customizable printing platform can help stimulate a vibrant biomaker community of engineers, biologists, and educators.

bioengineering↗

bioRxiv2022

Androgen receptor condensates as drug targets

Transcription factors are among the most attractive therapeutic targets but are considered largely undruggable due to the intrinsically disordered nature of their activation domains. Here we show that the aromatic character of the activation domain of the androgen receptor, a therapeutic target for castration resistant prostate cancer, is key for its activity as a transcription factor by allowing it to partition into transcriptional condensates. Based on this knowledge we optimized the structure of a small molecule inhibitor, previously identified by phenotypic screening, that targets a specific transactivation unit within the domain that is partially folded and rich in aromatic residues. The optimized compounds had more affinity for their target, inhibited androgen receptor-dependent transcriptional programs, and had antitumorigenic effect in models of castration-resistant prostate cancer in cells and in vivo. These results establish a generalizable framework to target small molecules to the activation domains of oncogenic transcription factors and other disease-associated proteins with therapeutic intent.

biochemistry↗