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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. 

Clinical use of pancreatic β islets for regenerative medicine applications requires mass production of functional cells. Current technologies are insufficient for large‐scale production in a cost‐efficient manner. Here, we evaluate advantages of a porous cellulose scaffold and demonstrate scale‐up to a wicking matrix bioreactor as a platform for culture of human endocrine cells. Scaffold modifications were evaluated in a multiwell platform to find the optimum surface condition for pancreatic cell expansion followed by bioreactor culture to confirm suitability. Preceding scale‐up, cell morphology, viability, and proliferation of primary pancreatic cells were evaluated. Two optimal surface modifications were chosen and evaluated further for insulin secretion, cell morphology, and viable cell density for human‐induced pluripotent stem cell‐derived pancreatic cells at different stages of differentiation. Scale‐up was accomplished with uncoated, amine‐modified cellulose in a miniature bioreactor, and insulin secretion and cell metabolic profiles were determined for 13 days. We achieved 10‐fold cell expansion in the bioreactor along with a significant increase in insulin secretion compared with cultures on tissue culture plastic. Our findings define a new method for expansion of pancreatic cells a on wicking matrix cellulose platform to advance cell therapy biomanufacturing for diabetes.