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The biocompatibility of materials used in electronic devices is critical for the development of implantable devices like pacemakers and neuroprosthetics, as well as in future biomanufacturing. Biocompatibility refers to the ability of these materials to interact with living cells and tissues without causing an adverse response. Therefore, it is essential to evaluate the biocompatibility of metals and semiconductor materials used in electronic devices to ensure their safe use in medical applications. Here, we evaluated the biocompatibility of a collection of diced silicon chips coated with a variety of metal thin films, interfacing them with different cell types, including murine mastocytoma cells in suspension culture, adherent NIH 3T3 fibroblasts, and human induced pluripotent stem cell (iPSC)-derived neural progenitor cells (NPCs). All materials tested were biocompatible and showed the potential to support neural differentiation of iPSC-NPCs, creating an opportunity to use these materials in a scalable production of a range of biohybrid devices such as electronic devices to study neural behaviors and neuropathies. 

Understanding protein secretion has considerable importance in biotechnology and important implications in a broad range of normal and pathological conditions including development, immunology, and tissue function. While great progress has been made in studying individual proteins in the secretory pathway, measuring and quantifying mechanistic changes in the pathway's activity remains challenging due to the complexity of the biomolecular systems involved. Systems biology has begun to address this issue with the development of algorithmic tools for analyzing biological pathways; however most of these tools remain accessible only to experts in systems biology with extensive computational experience. Here, we expand upon the user-friendly CellFie tool which quantifies metabolic activity from omic data to include secretory pathway functions, allowing any scientist to infer properties of protein secretion from omic data. We demonstrate how the secretory expansion of CellFie (secCellFie) can help predict metabolic and secretory functions across diverse immune cells, hepatokine secretion in a cell model of NAFLD, and antibody production in Chinese Hamster Ovary cells. 

Bio-hybrid devices, combining electronic and photonic components with cells, tissues, and organs, hold potential for advancing our understanding of biology, physiology, and pathologies and for treating a wide range of conditions and diseases. In this review, I describe the devices, materials, and technologies that enable bio-hybrid devices and provide examples of their utilization at multiple biological scales ranging from the subcellular to whole organs. Finally, I describe the outcomes of a National Science Foundation (NSF)–funded workshop envisioning potential applications of these technologies to improve health outcomes and quality of life. 

Recombinant heparin is produced by genetically engineered cells and provides an alternative to the current animal derived heparin. 

Background: Although most biologics are produced using recombinant technologies, heparin persists as a product purified from animal tissues. A cell based system for production of heparin would eliminate risk of supply shortage and contamination. Additionally, genetic engineering could yield heparin with improved qualities such as reduced risk of heparin-induced thrombocytopenia. Aims: This work is focused on engineering mammalian cell lines and bioprocess methods to produce recombinant heparin. Methods: The heparan sulfate biosynthetic pathway of mastocytoma cells was genetically engineered to alter the expression of heparan sulfate sulfotransferases. The resulting cell lines were screened for production of anti-FXa activity. Heparan sulfate production from a candidate cell line was tested in chemically defined medium. The recombinant product was characterized structurally and in clotting, anti-protease and heparin induced thrombocytopenia assays. Results: Engineered cells produced heparan sulfate in chemically defined medium with anti-Xa and anti-IIa activity exceeding the requirement for unfractionated heparin despite having lower sulfate content. Chain length was longer than unfractionated heparin. Additionally, binding to platelet factor 4 was reduced compared to unfractionated heparin, suggesting less risk of heparin-induced thrombocytopenia. Conclusion: These results demonstrate the feasibility of producing a substitute for unfractionated heparin from recombinant cell culture. Additionally, recombinant technology may allow production of heparin substitutes with improved properties such as reduced side effects.