# Antibacterial Bio-Based Polymers for Cranio-Maxillofacial Regeneration Applications
## 4 Cements
### Polymethyl Methacrylate-Based Cements  
PMMA-based cements are composed of both a liquid monomer and a solid phase of PMMA and/or other co-polymers as powder. Polymerization occurs when amino and benzoyl-peroxide groups of each phase react, emitting high doses of energy in the form of heat, which in turn limits their applicability in great volumes. Moreover, the other major concern about these resins is their inert behavior, which often leads to bacterial colonization. For this reason, cement-soaking with antibacterial agents was one of the first ways to avoid infections. However, this approach resulted in a diminishment of the mechanical properties of the cements. In this sense, the use of bio-based polymers can fulfill these necessities via reinforcing the mechanical properties of antibacterial-soaked cements or using bio-based polymers with antibacterial properties. [PERSON] et al., tested (in vivo) the effect of quaternized chitosan (hydroxypropyltrimethyl ammonium chloride chitosan, HACC)-loaded PMMA bone cement on methicillin-resistant _S. aureus_ (MRSA)-infections of the tibial metaphysis in a rabbit model, infections which are specially difficult to overcome due to antibiotics resistance. By using this quaternized chitosan, they obtained much better antibacterial results in comparison to the gentamycin-loaded and the chitosan-loaded cements. Moreover, bone lysis, cyst formation and sequestral bone formation was observed in the control, gentamycin-loaded and chitosan-loaded cements while they were not in the HACC-loaded PMMA, obtaining the lowest histopathological scores among all the conditions [107]. [PERSON] et al. studied (in vitro) the effect of loading chitosan and quaternary ammonium chitosan-nanoparticles into PMMA cements with, or without, additional gentamycin. On the one hand, they demonstrated that the addition of the nanoparticles did not alter the mechanical properties of the cement and provided antibacterial effects against _S. aureus_ and _S. epidermidis_[108]. The best antibacterial results were achieved with the quaternary ammonium chitosan nanoparticles, which was in agreement with other authors, probably because of its higher surface density when compared to chitosan, as explained in [109]. Figure 5: Schematic illustration of pendent eugenyl residues from the polymeric network on the surface of the composites (**A**), and images of composites surface antibacterial activity assay according to the ISO 22196:2007 after 24 h of incubation (**B**). Adapted from [PERSON] et al. 2016 [105], with permission from Elsevier. In contrast, [PERSON] et al. loaded chitosan hydrogels into PMMA cements obtaining antibacterial composites with good mechanical properties [110; 111]. In a first work, they functionalized a PMMA-based commercial cement with a hydrogel of chitosan and poly(vinyl alcohol) (PVA) containing nano-sized hydroxyapatite and silver ions. The inclusion of hydrophilic hydrogels like that one within PMMA matrixes creates a porous structure which is beneficial for bone growth, upgrading a bioinert PMMA resin into a bioactive composite which could induce crystals formation. Moreover, the addition of nano-sized hydroxyapatite promoted the formation of a dense layer of apatite on the surfaces of the pores while silver ions provided the antibacterial properties (Figure 6) [111]. In a subsequent work, the authors loaded a quaternized chitosan derivative (HACC)-glycerophosphate hydrogel, which provided both mechanical, antibacterial and osteogenic properties to the cement, diminishing the number of components. Furthermore, it lowered the maximum temperature value of the setting reaction to less than 30 \({}^{\circ}\)C while increasing the working time [110]. Figure 6: Contact bacteriostatic (**A**) and sustained-release bacteriostatic (**B**,**C**) of polymethyl methacrylate (PMMA)-based cements in _E. coli_ and _S.