## 3 New GTR and GBR Using Tissue Engineering
### Scaffold-Based Tissue Engineering  
The scaffolds act as a mechanical structure to support cell infiltration and revascularization. Their design should consider biochemical properties and degradation kinetics to mimic original tissue biology. The external and internal geometry can be referred to as a three-dimensional (3D) scaffold which promotes cell adhesion, proliferation, differentiation, and bone mineral deposition [64; 65].  
In designing 3D scaffolds, the following concerns must be considered: (1) proper architecture such as porosity, pore size, and interconnectivity; (2) mechanical properties to bear the external force during regeneration; (3) physical properties like hydrophilicity, roughness, and surface topography; (4) biocompatibility like cell affinity; (5) biodegradability in harmony with bone maturation; (6) sterilizability without loss of bioactivity; and (7) controlled deliverability of bioactive molecules or drugs [64; 65]. Human cancellous bone has a total porosity from 30% to 90%, and cell interaction occurs within the voids [66]. Several preclinical and clinical studies suggest that scaffolds for alveolar bone regeneration should have 70% overall porosity [66; 67]. When it comes to the pore diameter, a range between 150 \(\upmu\)m to 500 \(\upmu\)m promotes vascularization and infiltration of new cells and tissues without compromising mechanical strength [66]. Not only the presence of pores, but also the interconnection between them is crucial in cell growth within the network and prevention of core necrosis [68]. The physical properties are closely related to biomaterials utilized to make the scaffold [64; 65]. The scaffold should have biocompatibility, bioactivity, and non-cytotoxic effects [68]. Also, adequate hydrophilicity and roughness, and specific surface nanotopography should be developed to replicate the natural process of bone regeneration [69]. Nanotopography increases the surface area, surface-to-volume ratio, and surface roughness [70]. Finally, the control of the scaffold degradation process is the most critical key in successful tissue regeneration. In the early days, even tissue ingrowth was not actual regeneration; however, the sign of direct immature tissue filling was considered a sign of scaffold degradation. Thus, scaffold degradation was faster than tissue remodeling and maturation, which made proper regeneration fail [60]. The onset of scaffold degradation should be followed after tissue remodeling within the scaffold at least once in the natural remodeling cycle [71]. Recently, the concept of scaffolds changed to have sufficiently elongated mechanical strength to bear collapse during tissue maturation. In order to harmonize with dentoalveolar remodeling, scaffold degradation within 5-6 months is considered appropriate [71]. Using this paradigm, a multiphasic scaffold with a different structure and chemical composition was introduced for periodontal regeneration [64]. As the periodontium is a complex of soft and hard tissues, different features of each scaffold layer can induce functionally oriented PDL into the alveolar bone and the cement over time [64]. A 0.0250-mm-thick space to mimic PDL space and to prevent tooth ankylosis was tried in one study and showed positive results [72].