## 4 Discussion

Table 4: Properties of different metal-based fillers and corresponding techniques used in manufacturing scaffolds. conductivity under biological conditions compared to other conductive polymers. Its great stability and biocompatibility make it the most suitable also for in vivo applications in neural engineering [101; 102; 103; 104; 105]. Further, it was shown to enhance cell attachment, differentiation and to improve gene expression level and nerve regeneration. The need to combine PPy with other materials mainly comes from its poor mechanical properties. Thus, while pure PPy is crystalline and brittle, not proper for tissue scaffold materials [117], PPy composite can provide the necessary mechanical properties, while keeping the beneficial conducting and biocompatible properties of PPy. A similar requirement can be highlighted for PEDOT. It possesses better conductivity, thermal stability, electrical, chemical, and environmental stability compared to other conductive polymers, which makes it ideal for providing a continuous stimulation. However, due to its limited processability, it needs to be combined with other kinds of mechanically supporting materials, such as polymers or hydrogels. Thus, it is usually used as coating for fibers of other structures to enhance the conductivity and ensure a proper stimulation to neuronal cells. This was shown to have a positive effect on the development of nerve conduits for axonal regeneration [105; 106]. Among conductive additives, both gold and carbon were employed in several works due to their biocompatibility and great electrical properties to stimulate neuronal cells, thereby enhancing their proliferation. The use of silver was shown to be limited to its antimicrobial properties, thus to avoid bacteria contamination. Despite very promising results could be obtained from in vitro testing, still several concerns exist about the safety of materials or \(Ag\) fillers used for conductance due to their lack of degradability, an important issue if aiming to nerve regeneration in vivo. In this picture, an interesting material, which needs to be pointed out is ZnO. In [99; 100] zinc nanoparticles were proposed as biodegradable and conductive filler for nerve regeneration, and the resulting effect on the promotion of neuroglial cell proliferation suggest this material as a potential candidate for further future investigations. Regarding cardiac tissue engineering applications, the highlighted key requirements are related to the elasticity and the possibility to tune the conducting characteristics, in order to effectively reproduce the well-known behavior of excitation-contraction coupling of the heart, thus ensuring the propagation of electrical signals in a synchronized mode. PANI with its unique tunable electrical properties [50; 51; 52; 53; 54] and PPy with its ability to be easily combined with other polymers to form a composite material with required mechanical characteristics [40; 41; 42] are the most suitable conductive polymers for realizing an engineered tissue that could be suitable for integration with cardiac muscle. With both these materials, an improved adhesion and proliferation of cardiac myoblasts could be observed. Furthermore, supporting the differentiation of these cells into cardiac myocytes, these materials are promising candidates to facilitate the regeneration of cardiac tissue in presence of defects. Interestingly, also nanostructured gold and carbon-based materials were highlighted as extremely promising for improving the regeneration of cardiac defects. Incorporating nanoscale electro-conductive gold nanoparticles into an injectable hydrogel was shown to enhance the properties of myocardial constructs, with extremely powerful potential implication aiming at an injectable smart scaffold [94]. Similarly, nanostructured carbon has been demonstrated as potential strategy to improve the expression of cardiac-specific genes involved in muscle contraction and electrical coupling [83].