Once the model was validated, it has been used to simulate a quantified understanding of the previously inaccessible local environment, demonstrating the time-dependent changes in the local pH and other species concentrations. The predictive nature of this FEM could then allow the solution composition to be iterated for the best experimental system performance and highest simulated current densities, which were then validated experimentally. Once the local environment had been optimised for the enzymatic HER and CO2RR on mesoporous electrodes, a novel electrode architecture was introduced to demonstrate the applicability of the conclusions on electrolyte composition to a different system. Hierarchical inverse opal (IO) electrodes were chosen due to their macro and mesoporous structure which enables increased enzyme loading compared to purely mesoporous electrodes, as has been previously demonstrated. A shift to TiO2 also allowed the application of more negative reduction potentials (-0.8 V vs. SHE) than that being used with mesoITO (-0.6 V vs. SHE) due to the degradation of ITO at more reducing potentials. The IO-TiO2 electrodes were constructed with co-assembled ~21 nm anatase TiO2 particles and 750 nm diameter polystyrene spheres and then annealed to give IO macropores with a total film thickness of 40 μm (Figure ). With these electrodes the principles of local chemical environment adjustment for enzymatic electrochemistry were applied and hence significant improvements in the current density were again achieved. same buffer capacity at a bulk pH 6.54 (Figure ). The mesoITO|H2ase electrode in the MOPS electrolyte solution displayed 60% higher catalytic activity for proton reduction than the MES solution at an applied bias of -0.6 V vs. SHE (Figure ). The H2 produced was measured by gas chromatography of a sample of the reaction headspace and a Faradaic efficiency (FE) of (88 ± 5)% was determined (Figure ). The average current density of the repeats, with a new bioelectrode in new electrolyte for each repeat, has been shown as the solid line with the standard deviation (N ≥ 3) as the shaded area/error bars. The reproducibility of the system is demonstrated by the narrow standard deviation of both the current density and the product quantification. Voltammetry of the mesoITO|H2ase and mesoITO electrodes are also shown in Figure , showing minimal current density for the enzyme-free control electrodes.