*7.1. Hydrogel Materials*

## 7.1.1. Hydrogel Classifications

Hydrogels are classified based on raw materials, chemical composition, physical structure, type of crosslinking, physical appearances and electrical charge, presented in Table 1.


#### **Table 1.** Classification of hydrogels.

## 7.1.2. Polymer Materials Used for Articular Cartilage Synthesis

Table 2 presents comparative advantages and applications of wide ranges of materials in synthesizing polymeric hydrogels for articular applications.

**Table 2.** Commonly used polymers in articular cartilage synthesis.


\* METAC: 2-(methacryloyloxy)ethyltrimethlammonium chloride.

#### *7.2. Synthesis of Hydrogels*

#### 7.2.1. Crosslinking Hydrogels

Various crosslinking approaches have been reported to synthesize hydrogel, such as chemically modified process, crystallization process, free-radical polymerization and ionic polymerization [127,128]. Table 3 presents four prevalent approaches that are used to synthesize hydrogels for medical applications.


**Table 3.** Crosslinking methods to design hydrogels.

The major limitations for the biomedical application of hydrogels are the nonbiocompatibility of some hydrogels and potential toxicity of residual unreacted small crosslinkers in chemically crosslinked hydrogels [135]. However, among methods mentioned above, free-radical polymerization is a prevalent method used to synthesize hydrogels for biomedical applications [136].

#### 7.2.2. Free Radical Polymerization

Free radical polymerization (FRP) is a capable technique to produce about 50% of monomers to polymers [137]. The major advantage of FRP is its insensitivity to monomer and impurities compared to ionic polymerization [138]. It can be applied in normal room conditions, which minimize the cost of production. A broad range of monomers can be utilized in FRP to turn to polymers which is the great advantage of this technique [139].

Free radical polymerization involves the conversion of monomers into polymers through the initiation, propagation and termination steps. The ''initiation" process involves

the production of radicals that start the reaction with monomer. An existing free-radical interacts with the monomer resulting in a new radical, which in turn opens another molecule monomer. This process repeats to result in a polymer, and this step is called ''propagation". The polymerization reaction stops when the last radical of one polymer chain meets another chain with the free radical, and when they combine, the polymerization process is completed, hence the "termination" step [140].
