There is a growing interest in the design and engineering of operational biofuel cells that can be implanted. This review highlights the recent progress in the electrochemistry of biofuel cell technologies, but with a particular emphasis on the medical and physiological aspects that impact the biocompatibility of biofuel cells operating inside a living body. We discuss the challenge of supplying power to implantable medical devices, with regard to the limitations of lithium battery technology and why implantable biofuel cells can be a promising alternative to provide the levels of power required for medical devices. In addition to the challenge of designing a biofuel cell that provides a stable level of sufficient power, the review highlights the biocompatibility and biofouling problems of implanting a biofuel cell that have a major impact on the availability of the substrates inside body that provide fuel for the biofuel cell. These physiological challenges and associated ethical considerations are essential to consider for biofuel cells that are designed to be implanted for long-term operation inside a living animal and eventually to human clinical applications.

Because accessing the small intestine is technically challenging, studies of the small intestinal microbiome are predominantly conducted in patients rather than in healthy individuals. Invasive clinical procedures, such as endoscopy or surgery, usually performed for therapeutic purposes, are typically required for sample collection. Although stomas offer a less invasive means for repeated sampling, their use remains restricted to patient populations. As a result, the small intestinal microbiome of healthy individuals remains largely understudied. This study evaluated a novel ingestible medical device for collecting luminal samples from the small intestine. A monocentric interventional trial (NCT05477069) was conducted on 15 healthy subjects. Metagenomics, metabolomics, and culturomics were used to assess the effectiveness of the medical device in characterizing the healthy small intestinal microbiome and identifying potential biomarkers. The small intestinal microbiota differed significantly from the fecal microbiota, displaying high inter-individual variability, lower species richness and reduced alpha diversity. A combined untargeted and semi-targeted LC–MS/MS metabolomics approach identified a distinct small intestinal metabolic footprint, with bile acids and amino acids being the most abundant metabolite classes. Host- and host/microbe-derived bile acids were particularly abundant in small intestinal samples. Using a fast culturomics approach on two small intestinal samples, we achieved species-level characterization and identified 90 bacterial species, including five potentially novel ones. This study demonstrates the efficacy of our novel sampling device in enabling comprehensive small intestinal microbiome analysis through an integrative, multi-omics approach. This approach allows distinct microbiome signatures to be identified between small intestinal and fecal samples.

We discuss the perspectives of designing implantable medical devices that have the criterion of being symbiotic. Our starting point was whether the implanted device is intended to have any two-way (“duplex”) communication of energy or materials with the body. Such duplex communication extends the existing concepts of a biomaterial and biocompatibility to include the notion that it is important to consider the intended functional use of the implanted medical device. This demands a biomimetic approach to design functional symbiotic implantable medical devices that can be more efficient in mimicking what is happening at the molecular and cellular levels to create stable interfaces that allow for the unfettered exchanges of molecules between an implanted device and a body. Such a duplex level of communication is considered to be a necessary characteristic of symbiotic implanted medical devices that are designed to function for long periods of time inside the body to restore and assist the function of the body. We illustrate these perspectives with experience gained from implanting functional enzymatic biofuel cells.