# Material Design in Implantable Biosensors toward Future Personalized Diagnostics and Treatments
## 5 Challenges and Future Perspectives  
Creating implantable biosensors comes with significant obstacles, including the foreign-body response, stability, and biosensor response, as well as the need for continuous monitoring, power supply, and data transmission. Overcoming these obstacles requires meeting specific criteria, such as utilizing more adaptable and biocompatible biomaterials, achieving miniaturization, and ensuring reliability. The implementation of these design parameters is essential in the development of implantable biosensors [84, 85]. Some of the present and anticipated benefits of implantable biosensors for healthcare systems and the general public can be found in Table 3.  
Various concerns should be considered and thought of in advance to design and then apply an ideal implantable biosensor. As aforementioned, biocompatibility of the design materials to avoid any unfavorable reactions in the body is the first and most crucial factor [86]. With developing science, many implantable sensors have shown minor cell injury. However, the materials used in long-term working biosensors (years or even a lifetime) must be biodegradable and biocompatible. For short-term strategies (e.g., digestible biosensors), high biocompatibility is demanded for both the instrument and the degraded products. In addition, some new synthetic biology and gene engineering strategies are being explored to generate biomolecule-based functional materials for the construction of the sensor. These techniques manipulate or mimic biomolecules to produce advanced functions. Additionally, the degradation of the implantable sensors can be controlled by following the manipulation processes theoretically inside cells. Besides biocompatibility, the device should show lasting stability, accuracy, selectivity, miniaturization, downscaled power, and portability. The label-free electrochemical implantable biosensors with the promising features cited earlier have gotten tremendous attention in this field. Integrating nanomaterials and nanotechnology in the biosensor field could improve biosensors' performance and functionality and solve the main problematic issues in designing biosensors [87]. Many reports of in vivo biomedical devices are used for accurate, stable, simultaneous, and continuous monitoring. Developing a completely lab-on-chip system was a huge step toward creating wireless implantable bioch sensors [88]. Figure 10: Schematic comparison between non-thermo-responsive and thermo-responsive hydrogels on immune cell response and fibrous capsule formation after 7\(-\) and 30\(-\)days post-implantation (**A**). \({}^{*}\), \({}^{**}\) and \({}^{***}\) represent statistical significance (\(p<0.05\)\(p<0.01\) and \(p<0.001\)). Various surface patterns of PDMS and their impact on macrophage number and capsule thickness between 2 and 8-weeks post implantation (the black arrows demonstrate fibrous formation) (**B**). Reproduced with permission from ref. [83]. Copyright © 2020, The Korean BioChip Society and Springer. Additionally, implantable bio-micro-electromechanical systems (bio-MEMS) could prove their in-situ monitoring ability of blood flow. [PERSON] et al. fabricated an intelligent and wireless bio-MEMS for non-invasive and early stenosis diagnosis in heart bypass grafts [89]. Despite this achievement, the accurate evaluation of health status requires the detection of more health-related biomolecules as targets. In this case, optimal interactions between the probe and the targeting biomolecules with better anti-fouling is needed for the development of an ideal sensing interface. For instance, a biomolecule may function as a sensing layer, and a detection probe or an implantable biosensor may have multiplexed array constructions. In addition, developing multiplexed arrays of nanosensors that are responsive to a set of targets (molecules, viruses, enzymes, and chemicals) is an outstanding achievement in creating the next generation of implantable biosensors.