How host and microbial factors combine to structure gut microbial communities remains incompletely understood. Redox potential is an important environmental feature affected by both host and microbial actions. We assessed how antibiotics, which can impact host and microbial function, change redox state and how this contributes to post-antibiotic succession. We showed gut redox potential increased within hours of an antibiotic dose in mice. Host and microbial functioning changed under treatment, but shifts in redox potentials could be attributed specifically to bacterial suppression in a host-free ex vivo human gut microbiota model. Redox dynamics were linked to blooms of the bacterial family Enterobacteriaceae. Ecological succession to pre-treatment composition was associated with recovery of gut redox, but also required dispersal from unaffected gut communities. As bacterial competition for electron acceptors can be a key ecological factor structuring gut communities, these results support the potential for manipulating gut microbiota through managing bacterial respiration.
Vascular endothelial growth factor (VEGF) and dexamethasone (DX) release from hydrogel coatings were examined as a means to modify tissue inflammation and induce angiogenesis. Antibiofouling hydrogels for implantable glucose sensor coatings were prepared from 2-hydroxyethyl methacrylate, N-vinyl pyrrolidinone, and polyethylene glycol. Microdialysis sampling was used to test the effect of the hydrogel coating on glucose recovery. VEGF-releasing hydrogel-coated fibers increased vascularity and inflammation in the surrounding tissue after 2 weeks of implantation compared to hydrogel-coated fibers. DX-releasing hydrogel-coated fibers reduced inflammation compared to hydrogel-coated fibers and had reduced capsule vascularity compared to VEGF-releasing hydrogel-coated fibers. Hydrogels that released both VEGF and DX simultaneously also showed reduced inflammation at 2 weeks implantation; however, no enhanced vessel formation was observed indicating that the DX diminished the VEGF effect. At 6 weeks, there were no detectable differences between drug-releasing hydrogel-coated fibers and control fibers. From this study, hydrogel drug release affected initial events of the foreign body response with DX inhibiting VEGF, but once the drug depot was exhausted these effects disappeared.
The importance of biomechanics in glucose sensor function has been largely overlooked. This article is the first part of a two-part review in which we look beyond commonly recognized chemical biocompatibility to explore the biomechanics of the sensor-tissue interface as an important aspect of continuous glucose sensor biocompatibility. Part I provides a theoretical framework to describe how biomechanical factors such as motion and pressure (typically micromotion and micropressure) give rise to interfacial stresses, which affect tissue physiology around a sensor and, in turn, impact sensor performance. Three main contributors to sensor motion and pressure are explored: applied forces, sensor design, and subject/patient considerations. We describe how acute forces can temporarily impact sensor signal and how chronic forces can alter the foreign body response and inflammation around an implanted sensor, and thus impact sensor performance. The importance of sensor design (e.g., size, shape, modulus, texture) and specific implant location on the tissue response are also explored. In Part II: Examples and Application (a sister publication), examples from the literature are reviewed, and the application of biomechanical concepts to sensor design are described. We believe that adding biomechanical strategies to the arsenal of material compositions, surface modifications, drug elution, and other chemical strategies will lead to improvements in sensor biocompatibility and performance.
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