## 3 New GTR and GBR Using Tissue Engineering
### Biomaterial Scaffold for Bone Cell Infiltration
#### 3.3.1 Natural Polymers: Collagen, Alginate, Chitosan, and Hyaluronic Acid  
Natural polymers were adopted as the first biomaterials because of their high biocompatibility, proper cell recognition, enhanced cellular interaction with surrounding tissue, and hydrophilicity [73]. Based on these properties, they were investigated as hydrogels containing cells inside and showed successful results [73; 74]. Collagen is the most abundant protein found in bone, and it provides biocompatibility and structural stability to many tissues [75]. The collagen matrices promote cell adhesion, proliferation, and osteogenic differentiation of bone-marrow stromal cells in vitro [75]. The limitations of collagen, such as low mechanical strength, were improved by modifying collagen cross-linking [76; 77; 78]. Similarly, the denatured form of collagen, called gelatin, enhances osteoblastadhesion, migration, and mineralization based on biological groups [75]. Alginate is a natural material derived from brown algae which forms a gel in contact with water [79]. It is a polysaccharide and is highly accessible to make various forms of scaffolds, and it is easy to encapsulate living cells [79]. The viscosity and the porosity of alginate enable cellular immobilization, integration, and the extended release of factors and cells from the scaffold [80]. To overcome the low mechanical strength, alginate is often combined with other compounds such as chitosan, gelatin, and hydroxyapatite to improve osteoconductivity [80; 81]. Another essential feature of alginate is its factor-releasing effect to enhance cell affinity and angiogenesis [82; 83]. In the polysaccharide group, chitosan is another popular biomaterial based on its antibacterial and antifungal effects [84]. When applied in a scaffold, chitosan accelerates wound healing by avoiding infection of the operation site and preventing exposure of the wound. Hyaluronic acid is another natural polymer and is an essential element in wound healing by aggregating glycosaminoglycans (GAG) in the joint capsule [85]. Hyaluronic acid combines with other compounds to enhance mechanical properties and often contains growth factors for additional regenerative potential [86; 87]. Despite their advantageous biological properties, natural polymers showed a lack of bioactivity for promoting bone tissue regeneration, as well as a rapid degradation rate related to low mechanical strength [79; 88]. To overcome those limitations, natural polymers are usually combined with bioactive materials (i.e., bioceramics) or mechanically strong materials (i.e., synthetic polymers or metals) [89]. 3.2 Synthetic Polymers: Polycaprolactone (PCL), Polyethylene Glycol (PEG), Polylactic Acid (PLA), Polyglycolic Acid (PGA), and Polylactic-\(\infty\)-Glycolic Acid (PLGA)  
Synthetic polymers are utilized for their low cost and their ability to be produced in large quantities with a long shelf life [90]. PCL is a biodegradable compound which has mechanical strength and manufacturability for bone TE. With the help of many processes such as photopolymerization and 3D printing, PCL can have a porous structure [91], and this structure can be used to seed mesenchymal cells and growth factors to improve regeneration [92]. PCL also has biocompatibility and a remarkably slow degradation rate [93]. However, PCL is hydrophobic, which is responsible for low cell affinity and poor cellular response [94]. Similar to PCL, PLA and PLGA are hydrophobic. PEG has low toxicity, in addition to being hydrophilic and soluble. However, it shows a higher degradation rate than PCL [95]. Synthetic polymers degrade via hydrolysis within the interior part of biomaterial, resulting in an empty shell formation [96]. These features make them useful for bone graft materials, but not suitable for a drug-delivery system. Also, their acidic byproducts during degradation induce tissue necrosis and resultant exposure of the scaffold [61]. Therefore, bioceramics are usually combined with synthetic polymers to enhance bioactivity and to neutralize the acidic byproducts [97].