*2.2.1.2 Organic nanomaterial based nanocomposite hydrogels*

Organic nanomaterials, such as dendrimers, liposomes, hyperbranched polymers, and micelles, are some typical polymer NPs that have a wide range of applications in tissue engineering, drug delivery, and cancer immunotherapy. For example, the properties of polymer NPs (such as conductivity) can be adjusted to achieve the repair of myocardial infarction. Particle size and shape are the most widely studied and reported properties, as they affect blood circulation time, cellular uptake, antigen presentation, and T-cell immunity. *In vivo* studies of nanocomposite hydrogels have shown that changing the shape of nanoparticles can lead to changes in the immune

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

#### **Figure 3.**

*Design and fabrication of organohydrogel fibers [34]. (a) Molecular design of hybrid crosslinked polymeric network in organohydrogel fibers and schematic of the wet-spinning process and molecular evolution of hydrogel fibers. (b) Schematic of the preparation of organohydrogel fibers from hydrogel fibers by displacement solvent. (c) Photograph of a long single fiber collected on a continuously winding drum spool. (d) Schematic and photograph of an organohydrogel-fiber knitted textile.*

response. Compared with larger sizes, smaller size nanoparticles show better immune responses due to their larger specific surface area and higher reactivity (**Figure 3**).

#### *2.2.2 Fibers*

Fibrous scaffolds, a considerable option of mimicking the nanostructure of natural ECM, possess a more favorable morphology compared to porous scaffolds and hydrogels [35]. The nanofibers show similarity to the collagen fiber network, whose diameter distributes in the range of 50–500 nm. Besides, nanoscale fiber scaffolds with well-controlled pattern structures have received special attention in enhancing cell functions, such as cell adhesion, migration, proliferation, and differentiation, for their isotropic structure, uniform fiber size, and pore distribution, which also decide their mechanical properties [36]. Nanofiber scaffolds have been used in tissue engineering for heart, bone, cartilage, ligament, skeletal muscle, skin, and nerve tissue engineering, and as a carrier for the controlled delivery of drugs, proteins, and even DNA [37].

Nanocomposite fiber scaffolds can be obtained from polymers and nano-sized phases by molecular self-assembly, phase separation, and electrospinning manufacturing technology. Compared to the other two methods, electrospinning methods can produce fibers with controllable pore size, fiber size, and stiffness, making it the most widely studied technique [38]. Moreover, incorporating nanoparticles into electrospun fibers can improve biomimetic scaffolds because cell-matrix interactions are strongly affected by the presence of chemical cues that support cell attachment, proliferation, and differentiation.

#### **2.3 Preparation of tissue engineering nanocomposite scaffold materials**

The processing method of the above-mentioned nanocomposite scaffold is summarized as follows:

### *2.3.1 Blending*

This mixing method is the simplest preparation method and has many advantages. We can obtain NPs with specialized size by varying the stirring speed, material concentration, and preparation period. Additionally, the preparation process is easy for the separate preparation and cross-linking of NPs. Filippi et al. mixed PEG-functionalized iron oxide (II, III) nanoparticles with an average particle size of 15 nm and cells in sterile Trisbuffered saline to form a nanocomposite hydrogel network [39]. The obtained hydrogel has a smooth texture, possesses excellent mechanical properties, such as stress relaxation and high elastic modulus. However, the asymmetric distribution of nanoparticles in nanocomposite hydrogels and their diffusion behavior in solution needs to be further studied.

### *2.3.2 Solvent casting/particulate leaching*

A combination of solvent casting and particle leaching methods has been widely used to successfully manufacture 3D porous scaffolds [40]. It is a process of dispersing salts in polymers that are dissolved in organic solvents. The solvent is removed and then the salt crystals are leached out with water to form the porous scaffold. Utilizing this process, people can make a scaffold with a porosity value of up to 93% and an average pore diameter of about 500 μm by changing the size of the salt crystals and salt/polymer ratio [41]. However, this method cannot control certain key variables, such as pore shape and pore interconnectivity (**Figure 4**).

#### *2.3.3 Electrospinning*

Electrospinning is a special form of electrostatic atomization of polymer fluids. The biggest difference between the two is that the electrostatic spray uses a lowviscosity fluid, and the product is in the form of nanoparticles, which are mainly used for surface spraying. Electrospinning is a fluid with a higher viscosity, and the product is a nanofiber membrane, which is mainly used to prepare materials with three-dimensional shapes. Electrospinning is essentially a stretching process to generate long nanofibers of uniform diameter from a polymer solution in the electric field [42]. As the electrostatic interaction between the positively charged polymer and the collector increases, the droplets of the polymer solution become finer and stretch further, resulting in an ejection of fibers out of the solution.

This technique allows the production of bio-sized fibers with higher porosity and high surface area-to-volume ratio, making them promising candidates for tissue *Nanocomposite Biomaterials for Tissue Engineering and Regenerative Medicine Applications DOI: http://dx.doi.org/10.5772/intechopen.102417*

**Figure 4.** *Solvent casting/particulate leaching process [40].*

engineering and drug delivery applications. The increased cell surface area provides more cell attachment sites and allows for effective cell adhesion. Compared with synthetic polymers, natural polymers are generally less suitable for spinning. Therefore, for natural polymers, the polymer and solvent concentration optimization must be carefully optimized (**Figure 5**) [43, 44].

Electrospinning technology has been used to develop tissue engineering scaffolds. For example, hepatocyte-like cells from human mesenchymal stem cells (hMSCs) were observed to aggregate on PLLA co-PCL collagen (PLACL/collagen) nanofiber scaffolds to form functional liver spheres. The results indicate that the bioengineered PLACL/collagen nanofiber scaffold may be a promising candidate for the treatment of damaged hepatocytes in advanced liver failure [45]. Researchers have also used electrospinning to manufacture different types of nanocomposite scaffolds for tissue engineering applications, such as polyurethane/cellulose fiber scaffolds, and polyethylene terephthalate (PET) scaffolds [46–48]. The main advantage of nanofibers prepared by electrospinning technology is that it allows easy transport of nutrients and waste across the scaffold. However, there are still some limitations, the use of cytotoxic solvents and a wide range of optimization parameters, such as applied voltage, flow rate, and travel distance to obtain ordered nanofibers, urgently need to be resolved.
