## 3 Graphene and Graphene-Related Materials for Biological Applications
### Graphene and Related Materials as Tool for Regenerative Medicine and Tissue Repair  
The combination of graphene and graphene derivatives with plenty of different matrices has represented a game changing event in the production of biomaterials [119; 120]. Fixing or replacing both tissues and organs has been boosted by the graphene-based composites by combining biocompatible scaffolds due to a variety of surface interactions [121]. Tissue engineering is one of the frontiers of medicine, aiming to overcome the drawbacks of the classical transplant procedure through the production of hybrid materials able to perform the same activity as the tissues replaced [122]. Graphene and its related materials have shown very attractive results related to the production of polymeric composites with great mechanical performances together with high biocompatibility for several applications ranging from bone to soft tissue repair [123]. [PERSON] et al. [124] combined polyurethane with graphene for the production of conducting-polymer-based-material tissue regeneration. The authors aimed to grow L929 fibroblast and blood vessel endothelial cells on a membrane containing graphene flakes. This was particularly interesting in the case of endothelial cells. Indeed, they could be grown on the inner surface of tubular scaffolds by mimicking the native blood vessel structure [74]. The authors proved the ability of composites to support the attachment, spreading, and proliferation of cell lines. A very close approach was used by [PERSON] et al. [125] for the production of coated stents by using graphene oxide mixed with polyurethane. As shown in Figure 3, graphene-oxide-based composites create a stable coating on the surface of the stent without any tearing or ablation phenomenon. The modification of interphase properties due to the presence of graphene clearly increased the durability of the stent due to the radical-scavenging effect, which preserves the polymeric matrix from degradation promoted by extracellular fluids. Similar results could be achieved by using titanium-based materials [126], which however show the critical drawback of cellular morphology alteration. [PERSON] et al. [127] dispersed graphene oxide into fibrin hydrogel as scaffolds for bone repair proving an enhanced level of biocompatibility, alkaline phosphatase activity, and calcium deposits. This was particularly interesting due the difficulty of solid bone repairing by using polymeric composites and could lead the way to avoid the use of metal alloys [128], preventing the vicious effects related to metal release [129]. [PERSON] et al. [130] studied the use of an electroactive poly (p-phenylene sulphide) /chitosan mixed with rGO as a potential candidate for tissue engineering. These authors found that high biocompatibility was reached by using an rGO loading of up to 10 wt.% proving a cell attachment and a general porosity of up to 80%. Chitosan was also used in combination with GO and calcium silicate to produce a hierarchical microstructured biomaterial for wound dressing [131]. The authors aimed to reproduce the orderly, porous,  
Figure 3: Caption of polyurethane and graphene-oxide-based polyurethane (GO/PU) membrane before and after the coated stent durability test, as reported by [PERSON] et al. [125]. larmellar micron-scale structure of a healing wound, producing a material acting as wound dressing. It was also able to induce photothermal antibacterial and anticumour activity together with wound healing. [PERSON] et al. [132] moved a step forward and combined GO with silk's proteinaceous structure. Silk fibroin materials embedding GO showed an improvement of both mechanical and thermal properties of silk biomaterials, reaching a [PERSON]'s modulus of up to 1.65 GPa by using only 0.5 wt.% of filler. By in vivo studies, authors showed the improved cell adhesion, growth, and proliferation of fibroblast cells. Graphene and its related materials have boosted the use of poly(lactic acid) (PLA) as matrix for bone repair and tissue engineering [133]. [PERSON] et al.