## 3 Graphene and Graphene-Related Materials for Biological Applications
### Graphene and Related Materials as Tool for Regenerative Medicine and Tissue Repair
[134] combined PLA with GO and hydroxyapatite for the production of a high hardness and storage modulus, showing an efficient load transfer between the fillers and the polymeric matrix. These results outperformed those achieved by simply using polyglicolides stereocomplexes [135, 136] and inorganic composites [137]. Furthermore, PLA/poly(caprolactone) (PCL) blends have been used by [PERSON] et al. [138] for the preparation of electrospun fibres with high biocompatibility and a compatible morphology with bone engineering. Poly(ethylene) is another solid solution for the production of biomaterials containing graphene and related materials. [PERSON] et al. [139] dispersed graphene nanoplatelets into ultrahigh-molecular-weight poly(ethylene) for orthopaedic implants by using an electrostatic spraying technique. The authors reported that a graphene concentration of up to 0.1 wt.% induced an improvement of fracture toughness of up to 54% and tensile strength increment of up to 71%, while a filler concentration of 1 wt.% increased the elastic modulus and yield strength with a significant decrement of all other properties. The cytotoxicity of graphene nanoplates to osteoblasts was tested, and the authors showed that it is dependent on concentration and graphene agglomeration. Osteoblasts' survival decreased by up to 86% by using composites loaded with 1 wt.% filler, while composites with only 0.1 wt.% of graphene showed a survival reduction of only 16%. Similarly, [PERSON] et al. [140] studied high-density PE with GO by melt mixing, followed by compression moulding. The uniform dispersion achieved was a key point for the biocompatibility as mentioned before, and the authors achieved an optimum GO dispersion by immobilizing them on the PE surface through nucleophilic addition-elimination reaction. Authors achieved a yield strength of up to 20 MPa, an elastic modulus around 600 MPa, and an elongation-at-failure improvement of up to 70% by using a filler loading of up to 3 wt.%. Furthermore, authors successfully evaluated both the proteins' adsorption on the surface of composites and biophysical precursor process of cell adhesion by using serum albumin. As mentioned before, the presence of a small amount of graphene could dramatically improve the protein interaction on the interphase. Additionally, authors grew osteoblast and human mesenchymal stem cells lines on the composites by showing a significant increase in metabolic cell activity and proliferation. The other interesting class of biomaterials based on graphene and its related derivatives is represented by metal alloys [141]. Graphene promoted the strengthening mechanism of metal alloys due to its excellent bonding interfaces compared with that of traditional alloys [142]. There are still many challenges on the board such as the dispersion of graphene and its related materials into a metal matrix, which is generally done through chemical [143] or mechanical mixing [144] and electrode deposition methods [145]. All of these composites have found interesting biological applications [146]. [PERSON] et al. [147] electrochemically used rGO for the production of a cobalt /chromium alloy revealing an sp\({}^{2}\) bonding together with the presence of oxygenated groups at the interphase between rGO and the metal matrix. The authors tested the biocompatibility of this material by using mouse macrophage J774A.1 cell line, monitoring the ratio between lactate dehydrogenase and mitochondrial activities. Compared with the neat CoCr alloy, the rGO-based composite promoted the presence of well-distributed and well-shaped macrophages. Additionally, vimentin expression was unaltered, proving the enhanced biocompatibility. In vivo tests were run by survivor ability intraperitoneal injection in Wistar rats. The primary interaction with red blood cells showed a reduction of their size raising some concerns about the in vivo properties. Nonetheless, coatings produced by using GO have been used by [PERSON] et al. [148] to reduce the corrosion rate of magnesium alloy.