## 1 Introduction  
Mineralized bone is a fundamental connective tissue because it supports locomotion, protects the soft tissues and is the reserve of calcium and phosphate in the human body. It is highly remodeled thanks to a process that combines resorption due to osteoclasts and bone formation due to osteoblasts [1]. However, when large bone defects are present due to trauma or skeletal anomalies or when a disease causes an unbalanced regenerative process, as in the case of osteoporosis, bone regeneration is an important issue that requires specific treatments. In these cases, tissue engineering has been shown to offer promising approaches for bone regeneration, most of which are based on replacement with biomaterials that provide specific environments that promote bone formation. The ideal biomaterial should not only be biocompatible and safe, but should be osteoinductive and osteoconductive, also improving cell viability, adhesion, proliferation and osteogenic differentiation [2; 3]. Several biomaterials have been used for bone repair, such as collagen membranes (3D-COL) and polylactide (PLA). 3D-COL membranes have already been used in guided bone regeneration surgery, mainly for maxillofacial regeneration, for instance, to enclose the repaired site filled with bone autograft and promote faster bone healing [4; 5]. As shown in studies on animal models and in clinical applications for the regeneration of dental tissues, the composition and structure of these membranes are of fundamental interest as they influence the effectiveness of bone regeneration [5]. Bio-resorbable membranes made with natural materials, such as collagen and chitosan, have been shown to have excellent biocompatibility; however, they have different mechanical properties, with some of them having a very rapid degradation rate in vivo. In fact, a relatively rapid degradation of barrier membranes has proved to be a cause of spontaneous periodontal healing [6]. PLA is a hydrophobic aliphatic polyester with several biomedical and clinical applications [7]; it is one of the most used biomaterials in regenerative medicine because of its characteristics, as both PLA and its degradation products are biocompatible and safe [8]. For these reasons, PLA was successfully used to realize scaffolds for bone and osteochondral regeneration [9; 10]. The scaffolds can be cultured with cells, such as mesenchymal stem cells (MSCs), favoring bone regeneration through differentiation towards the osteogenic lineage or through the release of specific soluble factors. Alternatively, it is possible to functionalize the scaffolds with soluble molecules, which can then be released into the site to be regenerated, performing a therapeutic action [3]. In particular, MSCs are widely used in regenerative medicine as they can be recruited in different body districts, including dental tissues, and because of their multilineage differentiation potential [11]. In case of bone tissue engineering, MSC's ability to differentiate into osteoblasts has been widely studied [12]. Moreover, even if most of the studies were focused on bone marrow-derived MSCs, MSCs derived from other sites could offer some advantages, as in the case of MSCs derived from dental tissues, that can be easily isolated and have shown good performances in bone regeneration [13; 14; 15]. We have shown that these MSCs and their derivatives, such as conditioned medium (CM) and extracellular vesicles (EV), when seeded on appropriate biomaterials, are able to regenerate bone tissues, especially in calvary defects [16; 17; 18; 19; 20]. Among oral-derived MSCs, periodontal ligament (PDLSCs) and gingival (GMSCs) MSCs showed excellent performances in bone regeneration [16; 17; 18; 19; 20; 21; 22; 23; 24]. PDLSCs are very challenging in bone tissue engineering, showing a high capacity to proliferate, immunomodulatory competencies, ability to differentiate into osteogenic lineages, and also generating new bone after ectopic transplantation [25; 26; 27; 28].