# Silk Protein-Based Membrane for Guided Bone Regeneration
## 1 Introduction  
Guided bone regeneration (GBR) promotes new bone formation in bone defects using the barrier membrane [1]. The barrier membrane prevents the infiltration of the epithelial cells and the down growth of the connective tissue in the defect area [2]. It secures the space for the migration of osteoblasts and osteogenic cells and for new bone to grow in [2]. The barrier membrane must have several beneficial properties, such as biocompatibility, biodegradability without immune reaction, cell occlusion to prevent epithelial cell migration, the mechanical property for space making, tissue integration, and easy clinical handling [3]. However, there is no ideal barrier membrane that satisfies all of these properties. Generally, two types of the membrane have been used for GBR: resorbable and non-resorbable membranes [4]. Non-resorbable membranes, such as titanium mesh and titanium-reinforced expanded-polytetrafluoroethylene (e-PTFE), have high biocompatibility, mechanical properties, and stability [5]. They can stably maintain the form of grafted bone material and secure the space for bone growth [6]. The e-PTFE membrane effectively occludes the soft tissue cell invasion [7]. Even though non-resorbable membranes have had successful clinical outcomes in GBR, they can be more easily exposed in the oral cavity and lead to wound dehiscence compared with resorbable membranes [8], causing bacterial contamination on the membrane and potentially leading to the failure of the bone graft. Therefore, when membrane exposure occurs, it should be removed immediately [9]. Resorbablemembranes have been widely used in clinical practice due to their advantages with similar results as the non-resorbable membranes [10]. As the main source of the resorbable membrane, collagen has good biocompatibility, low risk of membrane exposure and donor site infection, and no need of a secondary surgery for removal [11]. However, collagen membranes have weak mechanical properties, rapid biodegradation, and lower space-making ability compared to non-resorbable membranes [10]. To overcome this problem, cross-linking membranes have been manufactured, but the agent used in the cross-linking can be cytotoxic during degradation [12; 13]. Silk derived from the silkworm _Bombyx mori (B. mori)_ is a natural biopolymer [14]. Silk is mainly composed of fibroin and sericin [14]. Silk fibroin (SF) has been used as a biomaterial after the removal of sericin by the degumming process [15]. Several types of SF material have been used for bone tissue engineering scaffolding, such as sponge, film, and hydrogel forms [16]. SF has excellent biocompatibility, biodegradation, oxygen and water permeability, and tissue integration [16]. Recently, the application of silk protein-based biomaterial for the GBR membrane has been reported [17; 18]. SF membranes have good osteogenic cell adhesion and induce new bone formation [17]. Although SF has excellent biological benefits as GBR membranes, it has weak mechanical properties and is difficult to handle [19]. The silk mat from cocoons, which is not the result of the degumming process, shows excellent mechanical properties [20]. This silk mat can be separated in different layers by eco-friendly methods [20; 21]. As a GBR membrane, it shows excellent tensile strength and comparable new bone regeneration in vivo [20; 22]. The clinical indication of the GBR procedure has been increased in the maxillofacial bone region [23]. GBR membranes are applied to the areas of bone defect after cyst and tumor excision, tooth extraction, and deficient alveolar bone for implant installation [11; 24]. However, commercially available GBR membranes have limitations according to their material, properties, and high prices [25]. The ideal GBR membrane has biological and mechanical properties, easy handling, and reasonable pricing [26]. Previously, various forms of silk protein-based membrane have been introduced for use in GBR [19].