*2.3.5 3D printing*

Traditional manufacturing techniques, such as electrospinning, freeze-drying, and solvent casting, have certain defects, including limited control over pore size, fiber arrangement, and pore interconnection, which can lead to poor nutrient transport or reduced cell survival and migration rates. 3D printing is one of the new methods to obtain highly ordered scaffolds. It provides a highly controllable and precise design for the internal structure and surface of the bracket. It can deposit cells and biological materials in a way that mimics the structure of biological tissues [53]. The principle of printing is based on a polymer solution containing cells or cell aggregates "biological ink," which is deposited layer by layer on a substrate to generate 3D structures, such as tissues or organs (**Figure 7**).

3D printing has been used to prepare a nanocomposite scaffold containing nano-HA and chondrogenic transforming growth factor-β1 (TGF-β1) in the highly porous subchondral bone layer. In the cartilage layer, the prepared scaffolds showed osteogenic differentiation, high biocompatibility with hMSC, and mechanical properties required for osteochondral tissue regeneration [55]. 3D printing is promising, but the

#### **Figure 7.**

*Integrated tissue-organ printer (ITOP) system [54]. (a) The ITOP system consists of three major units: (i) 3-axis stage/controller, (ii) dispensing module including multi-cartridge and pneumatic pressure controller and (iii) a closed acrylic chamber with temperature controller and humidifier. (b) Illustration of basic patterning of 3D architecture including multiple cell-laden hydrogels and supporting PCL polymer. (c) CAD/CAM process for automated printing of 3D shape imitating target tissue or organ. A 3D CAD model developed from medical image data generates a visualized motion program, which includes instructions for XYZ stage movements and actuating pneumatic pressure to achieve 3D printing.*

application of this technique in tissue engineering still needs to be explored due to high device costs, limited available materials, and low mechanical strength.

### *2.3.6 Self-assembly/self-organizing*

It is an effective method to generate well-organized and stable supramolecular structures through the spontaneously rearranging of molecules under thermodynamic equilibrium conditions. Self-assembly can occur spontaneously in nature through hydrogen and ionic bonds, hydrophobicity, etc., like the self-assembly of phospholipid bilayer membranes in cells. Molecular self-assembly is a useful method for generating supramolecular structures that rely relies on the potential of molecules to spontaneously rearrange themselves into well-organized and stable structures under thermodynamic equilibrium conditions. Such molecular interaction is non-covalent and can occur through hydrogen and ionic bonds, hydrophobicity, van der Waals forces, metal coordination, and electromagnetic interactions [56]. Self-assembly can occur spontaneously in nature, just like the self-assembly of lipid

*Nanocomposite Biomaterials for Tissue Engineering and Regenerative Medicine Applications DOI: http://dx.doi.org/10.5772/intechopen.102417*

#### **Figure 8.**

*Schematic representation of self-assembly/self-organizing [58].*



#### **Table 1.**

*Nanocomposites biomedical materials for tissue engineering applications.*

bilayer membranes in cells. Molecular self-assembly is a strategy to develop nanofiber materials with tissue engineering potential [57]. At the molecular scale, the precise and controlled application of intermolecular forces can lead to new and previously unachievable nanostructures. Thus, with proper design, the mechanical properties and release characteristics of the assembled material can be tailored specifically for its intended use through appropriate design (**Figure 8** and **Table 1**).
