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With the rapid development of micro systems technology and microelectronics, smart implantable wireless electronic systems are emerging for the continuous surveillance of relevant parameters in the body and even for closed-loop systems with a sensor feed-back to drug release systems. With respect to diabetes management, there is a critical societal need for a fully integrated sensor array that can be used to continuously measure a patient’s blood glucose concentration, pH, pCO2 and colloid oncotic pressure twenty four hours a day on a long-term basis. In this work, thin films of metabolite-specific or “smart” hydrogels were combined with microfabricated piezoresistive pressure transducers to obtain “chemomechanical sensors” that can serve as selective and versatile wireless biomedical sensors and sensor arrays for a continuous monitoring of several metabolites. Sensor response time and accuracy with which sensors can track gradual changes in glucose, pH, CO2 and ionic strength, respectively, was estimated in vitro using simulated physiological solutions. The biocompatibility and hermeticity of the developed multilayer encapsulation for the microsensor array has been investigated concerning the long-term stability and enduring functionality that is desired for permanent implants.