Betty Cai

All Publications

• Gelation of Uniform Interfacial Diffusant in Embedded 3D Printing ADVANCED FUNCTIONAL MATERIALS Shin, S., Brunel, L. G., Cai, B., Kilian, D., Roth, J. G., Seymour, A. J., Heilshorn, S. C. 2023

  View details for DOI 10.1002/adfm.202307435

  View details for Web of Science ID 001040672400001

• Spatially controlled construction of assembloids using bioprinting. Nature communications Roth, J. G., Brunel, L. G., Huang, M. S., Liu, Y., Cai, B., Sinha, S., Yang, F., Pașca, S. P., Shin, S., Heilshorn, S. C. 2023; 14 (1): 4346

  Abstract

  The biofabrication of three-dimensional (3D) tissues that recapitulate organ-specific architecture and function would benefit from temporal and spatial control of cell-cell interactions. Bioprinting, while potentially capable of achieving such control, is poorly suited to organoids with conserved cytoarchitectures that are susceptible to plastic deformation. Here, we develop a platform, termed Spatially Patterned Organoid Transfer (SPOT), consisting of an iron-oxide nanoparticle laden hydrogel and magnetized 3D printer to enable the controlled lifting, transport, and deposition of organoids. We identify cellulose nanofibers as both an ideal biomaterial for encasing organoids with magnetic nanoparticles and a shear-thinning, self-healing support hydrogel for maintaining the spatial positioning of organoids to facilitate the generation of assembloids. We leverage SPOT to create precisely arranged assembloids composed of human pluripotent stem cell-derived neural organoids and patient-derived glioma organoids. In doing so, we demonstrate the potential for the SPOT platform to construct assembloids which recapitulate key developmental processes and disease etiologies.

  View details for DOI 10.1038/s41467-023-40006-5

  View details for PubMedID 37468483

  View details for PubMedCentralID PMC10356773

• Gelation of Uniform Interfacial Diffusant in Embedded 3D Printing. bioRxiv : the preprint server for biology Shin, S., Brunel, L. G., Cai, B., Kilian, D., Roth, J. G., Seymour, A. J., Heilshorn, S. C. 2023

  Abstract

  While the human body has many different examples of perfusable structures with complex geometries, biofabrication methods to replicate this complexity are still lacking. Specifically, the fabrication of self-supporting, branched networks with multiple channel diameters is particularly challenging. Here, we present the Gelation of Uniform Interfacial Diffusant in Embedded 3D Printing (GUIDE-3DP) approach for constructing perfusable networks of interconnected channels with precise control over branching geometries and vessel sizes. To achieve user-specified channel dimensions, this technique leverages the predictable diffusion of crosslinking reaction-initiators released from sacrificial inks printed within a hydrogel precursor. We demonstrate the versatility of GUIDE-3DP to be adapted for use with diverse physiochemical crosslinking mechanisms by designing seven printable material systems. Importantly, GUIDE-3DP allows for the independent tunability of both the inner and outer diameters of the printed channels and the ability to fabricate seamless junctions at branch points. This 3D bioprinting platform is uniquely suited for fabricating lumenized structures with complex shapes characteristic of multiple hollow vessels throughout the body. As an exemplary application, we demonstrate the fabrication of vasculature-like networks lined with endothelial cells. GUIDE-3DP represents an important advance toward the fabrication of self-supporting, physiologically relevant networks with intricate and perfusable geometries.

  View details for DOI 10.1101/2023.04.02.535250

  View details for PubMedID 37066190

• 3D bioprinting of dynamic hydrogel bioinks enabled by small molecule modulators. Science advances Hull, S. M., Lou, J., Lindsay, C. D., Navarro, R. S., Cai, B., Brunel, L. G., Westerfield, A. D., Xia, Y., Heilshorn, S. C. 2023; 9 (13): eade7880

  Abstract

  Three-dimensional bioprinting has emerged as a promising tool for spatially patterning cells to fabricate models of human tissue. Here, we present an engineered bioink material designed to have viscoelastic mechanical behavior, similar to that of living tissue. This viscoelastic bioink is cross-linked through dynamic covalent bonds, a reversible bond type that allows for cellular remodeling over time. Viscoelastic materials are challenging to use as inks, as one must tune the kinetics of the dynamic cross-links to allow for both extrudability and long-term stability. We overcome this challenge through the use of small molecule catalysts and competitors that temporarily modulate the cross-linking kinetics and degree of network formation. These inks were then used to print a model of breast cancer cell invasion, where the inclusion of dynamic cross-links was found to be required for the formation of invasive protrusions. Together, we demonstrate the power of engineered, dynamic bioinks to recapitulate the native cellular microenvironment for disease modeling.

  View details for DOI 10.1126/sciadv.ade7880

  View details for PubMedID 37000873

• Enhancing Metabolome Coverage in Data-Dependent LC-MS/MS Analysis through an Integrated Feature Extraction Strategy ANALYTICAL CHEMISTRY Hu, Y., Cai, B., Huan, T. 2019; 91 (22): 14433-14441

  Abstract

  In untargeted metabolomics, conventional data preprocessing software (e.g., XCMS, MZmine 2, MS-DIAL) are used extensively due to their high efficiency in metabolic feature extraction. However, these programs present limitations in recognizing low-abundance metabolic features, thus hindering complete metabolome coverage from the analysis. In this work, we explored the possibility of enhancing the metabolome coverage of data-dependent liquid chromatography-tandem mass spectrometry (LC-MS/MS) results by rescuing metabolic features that are missed by conventional software. To achieve this goal, we first categorized the metabolic features into four confidence levels based on their chromatographic peak shapes and the presence of corresponding MS/MS spectra. We then assessed the false positives and quantitative accuracy of the metabolic features that contain MS/MS spectra but are not recognized by conventional software. Our results indicate that these missed features contain valid and important metabolic information and should be integrated into the conventional metabolomics results. Thus, we developed a data-preprocessing pipeline to extract low-abundance metabolic features and integrate them with the results from conventional programs. This integrated feature extraction strategy was tested on a set of fecal metabolomic data retrieved from mice who have undergone normal diet vs high-fat diet treatments. In our test data set, the integrated feature extraction approach increased the number of significant features being extracted by 24.4% and identified five additional metabolites bearing critical biological meanings. Our results show that this integrated feature extraction strategy remarkably improves the metabolome coverage beyond that of conventional data preprocessing, therefore facilitating the confirmation of metabolites of interest and accomplishment of a higher success rate in de novo metabolite identification.

  View details for DOI 10.1021/acs.analchem.9b02980

  View details for Web of Science ID 000498280100038

  View details for PubMedID 31626534