# Antibacterial Bio-Based Polymers for Cranio-Maxillofacial Regeneration Applications
## 1 Introduction
### Cranio-Maxillary Tissue Engineering  
In this review, we have focused on tissue regeneration, having limited our search to the cranio-maxillary region, a complex area which includes different structures such as the bones of the face (e.g., maxillary bones), the skull, dental organs and their surrounding tissues. In turn, all these structures are composed of both hard and soft tissues like bone, cartilage, epithelium, or periodontal tissues, thus presenting many pathologies which might require clinical intervention. On the one hand, there are many congenital, genetic disorders and multiple anomalies that interfere with bone development in the area of the skull and maxillary bones, which are encompassed under the collective term \"craniofacial syndromes\". They are directly associated with the development of bone and cartilage, affecting the form and function of the head and face [17], and include those associated with the oral cavity too. An illustrative example is the cleft lip/palate, a syndrome which occurs as a result of the non-fusion of the primary palate, causing a severe absence of bone in this area [2; 18]. These orofacial cleft conditions have been estimated to have a global annual prevalence of 7.94 cases per 10,000 live births with high variances of treated patients across regions and countries causing a high economic impact worldwide [1; 19; 20; 21]. In these cases, a replacement through autologous grafting would be required, but due to its invasiveness and high cost, there are other strategies like the use of hybrid scaffolds or composites which can replace the palatal, maxillary and the alveolar cleft defects [22]. On the other hand, there are multiple conditions which are not caused by a genetic malformation such as an alveolar atrophy, trauma-related pathological defects, odontogenic keratocysts, giant cell lesions, or ameloblastoma, among others. However, all these anomalies, and some clinical procedures (e.g., maxillary sinus elevation surgery), result in critical bone defects [2; 23; 24]. However, apart from the tissues' complexity, the most important issue regarding craniofacial syndromes and related dental procedures are the resident, pathogenic microorganisms found in these regions, and how they negatively influence the recovery of patients [25; 26]. The microbiota of the nasal and oropharyngeal cavities is predominantly composed of _Lactobacillus_ species and a variety of Gram-negative organisms such as _Staphylococcus_ and _Enterobacter_ species, among others, that can cause concomitant infections, resulting in severe medical pathologies like osteomyelitisitis or other chronic bacterial infections (e.g., periodontitis and peri-implantitis) [26; 27]. For all these reasons, there is a clinical need to develop biomaterials that meet the demands of each area to achieve tissues regeneration while having antibacterial properties to avoid secondary bacterial infections [27]. In this sense, the most clinically applied systems in oro-cranio-facial regeneration are (Figure 1):  
1. **Membranes for Guided Tissue/Bone Regeneration. ** During bone-regenerative treatments, soft tissues of the oral cavity tend to proliferate too and can impede the correct restoration of the area. For this reason, it is necessary to employ a physical barrier (a membrane) to exclude the gingival epithelium and connective tissue ingrowth, while enhancing the formation of bone and/or periodontal tissues [28; 29; 30; 31]. 2. **Scaffolds and Implanting Medical Devices for Soft and Hard Maxillofacial Tissues:** 1. **Hybrid scaffolds** act as extracellular matrix substitutes, improving cell viability, attachment, proliferation and differentiation, as well as vascularization, host integration, and load bearing. They are mainly used for cranial and maxillary regenerative therapies like preventing oroantral fistulae or for treating maxillary peri-implantitis [32; 33]. 2. **Dental implants** are a common choice for substituting missing teeth due to the excellent mechanical and chemical properties of the employed alloys.