# Material Design in Implantable Biosensors toward Future Personalized Diagnostics and Treatments
## 4 Coating Implantable Biosensors  
Foreign body reactions (FBRs) at the implant site is the main factor in losing the functionality of the implantable biosensors after insertion into the body [77]. The implantation of devices into the body causes tissue trauma, while the poor biocompatibility of the constructive materials causes biofouling, inflammation, and fibrous encapsulation. Thus, modifying the implantable biosensor to inhibit tissue reaction at the implant site is critical for biosensors in vivo applications. Polymers, including polyallylamine, pellethane(tm), polyethylene glycol, and horseradish peroxidase derivatives, are coating materials widely used for enhancing biosensors' biocompatibility and biodegradability due to the decrease in biofouling and FBRs [78,79]. For instance, [PERSON] et al. manufactured a copolymer composite from polyethylene glycol (PEG), 2-hydroxyethyl methacrylate (HEMA), and ethylene dimethacrylate for coating a glucose sensor [78]. The result of the biosensor's post-implantation demonstrated that the copolymer coating produces reliable sensitivities and less fibrous capsule formation after implantation, suggesting less of a foreign response reaction.  
Unfortunately, coating materials cannot entirely omit the inflammatory response, and generally, anti-inflammatory drugs are prescribed to control the inflammation throughout the lifetime of the biosensors [80]. Chronic consumption of these drugs can produce some significant effects. Therefore, from this point of view, drug-loaded polymeric coatings can be the best solution. The hydrophilic nature of traditional polymeric coatings prevents direct drug loading in their structure. The synthesis of hydrophilic polymers could vastly overcome the lack of traditional polymers for the encapsulation of drug molecules, while the diffusion problems due to high hydrophobicity become the main obstacle to using them as coating materials.  
Smart materials with the ability of fast analyte transmission to the sensing component and a controlled drug release during the lifetime of sensors are needed. Creating new coating materials for existing implantable biosensors is a lengthy and expensive procedure due to the need for an overall characterization, generation of a comprehensive understanding of the physicochemical features, and performing exhaustive toxicology studies. Thus, using existing materials and, more specifically, polymers is the logical strategy. Hydrogels (polymers with 3D structures) proved their ability as smart coating materials. For example, polyvinyl alcohol (PVA) hydrogels and PLGA microspheres permitted a fast influx of glucose via the hydrogel matrix combined with a gradual release of drugs from the microspheres [81]. An optimized smart polymer as a coating material should follow several critical features, including creating a uniform and homogenized structure with adequate adhesion over the sensor, long stability during the intended sensor life, and impact on the inflammation and vascularity of the surrounding tissues. Other than being biocompatible and anti-bifouling, hydrogels could show some merits, such as self-cleaning and thermo-responsiveness. For example, [PERSON] et al. proposed a hydrogel membrane with the ability of self-cleaning and thermos-sensitivity that can be utilized as a coating material in implantable biosensors with long-term functionality [82]. This hydrogel consisting of poly (N-isopropylacrylamide) and embedded polysiloxane nanoparticles can serve as a thermo-responsive double network nanocomposite hydrogel (DNNC). Besides traditional coating materials, DNNC-based hydrogel membranes could swell and de-swell in response to local body temperatures at the implant site (Figure 10). Additionally, the DNNC hydrogel membrane exhibited low macrophage numbers after post-implantation, meaning the membrane causes macrophages' detachment. As a result, this biocompatible coating improves biofunctionality, allowing its application in medical implants.