7.1.2. Biodegradable Trends of Various Conductive PEDOT-Based Scaffold Composites

The research focusing on scaffolds for biomedical applications has made significant strides with the advent of new technologies. The mechanical and electrical properties of scaffolds will affect the scaffold's biodegradation rate and biocompatibility [72,95–97]. Wang et al. (2017) experimented with varying weight percentages of PEDOT-HA nanoparticles in the fabrication of hyaluronic acid-doped PEDOT/chitosan/gelation porous conductive scaffolds [9]. They reported that the in vitro biodegradation of the scaffold had an inverse relationship with the weight percentage of PEDOT-HA. The scaffold displayed high biodegradability when there was a minute amount of PEDOT-HA. A large volume of PEDOT-HA enhanced the stability and biodegradation resistance of the scaffold. The addition of hydrophobic PEDOT likely reduced the hydrophilicity of the scaffolds [9].

**Table 3.** Biodegradation index of various composite scaffolds.



**Table 3.** *Cont*.

Wang et al. (2017) also researched PEDOT nanoparticles/chitosan/gelatinous porous scaffolds. They claimed that the presence of PEDOT nanoparticles significantly reduced the degradation rate of the scaffolds. Interestingly, the presence of PEDOT nanoparticles in the scaffold increased the cell viability. This is due to the genial interactions between the scaffold and the cell surface, which encourage cell proliferation and growth [40]. Another contribution from Wang et al. (2018) was the study of PEDOT/chitosan/gelatinous scaffolds for neural cells. The electrical conductivity of hydrated and dehydrated PEDOT/chitosan/gel scaffolds gradually diminished over time [10]. This observation could be attributed to the disintegration of the PEDOT layers on the surface of the chitosan/gelatinous matrix. The dissipation of PEDOT layers occurs when chitosan and gelatine are gradually degraded in the presence of the enzymes that are supposed to stimulate physiological conditions. Although the electrical conductivity of the scaffold reduced over time, as summarised in Table 3, it still met the electrical conductivity requirements for electrical stimulation in neural TE application.

Another study demonstrated that the addition of conductive PEDOT: PSS in nHAp/chitosan composite scaffolds using the lyophilisation method reduced the scaffold's biodegradability rate in the PBS solution. Although the scaffold with PEDOT: PSS had low biodegradability, its mechanical properties were consistent [26]. Lari et al. (2020) attempted to decrease the wettability, while dialling up the mechanical properties, of PEDOT: PSS/nHA/CS biocomposite, by integrating polycaprolactone (PCL) into the scaffold. PCL was selected due to its biodegradability and ease of blending with chitosan [5]. In another study, a PCL-CS-PPy conductive biocomposite nanofibrous scaffold is also a subject of interest in TE. The nanofibrous-structured scaffolds with sufficient biodegradability can be fashioned using electrospinning. It is worth mentioning that the mechanical properties decrease in tandem with the weight percentage of PPy. When the weight percentage of PPy used was reduced, it was easier for the scaffold to disintegrate, exhibiting the non-polymeric scaffold's typical mechanical behaviour [68].

In addition, Abedi et al. (2019) fabricated a conductive nanofibrous chitosan/PEDOT: PSS scaffold using the electrospinning method [25]. They reported that the addition of PEDOT: PSS in the scaffold may support cell growth without any toxic effects. Nonetheless, the biodegradability of the scaffold has yet to be explored. It was reported that the use of PEDOT: PSS in fabricating the scaffold did not change the biodegradability of the scaffold, due to the presence of alginate [98]. In addition, they also stated that an increase in PEDOT: PSS concentration in gelatine-alginate scaffolds could increase cell proliferation, although they did not report the cause. A takeaway from these studies is that the addition of CPs in the polymer matrix is a prerequisite for acquiring electrically conductive scaffolds. Adjusting the weight percentage of the CPs in the matrix composite of the scaffolds will affect their biodegradability. Therefore, further studies focusing on the relationship between the addition of CPs and the superior biodegradability of conductive scaffolds are warranted.

#### *7.2. Collagen-Based Scaffolds*

The addition of collagen or silk fibroin in scaffolds as biodegradable substituents can enhance their biodegradability, due to the nature of their proteins. Bioactive molecules, such as collagen, chitosan, and hydroxyapatite (HAp) were described as compatible, nontoxic, non-carcinogenic, non-immunogenic, and soluble in physiological conditions [13]. Due to these properties, the application of a collagen scaffold is prevalent in the field of damaged tissue regeneration [12,13]. Unfortunately, collagen is vulnerable to rapid degradation in body fluid or cell culture media [99]. The breakdown of collagen fibres depends upon the proteolytic action of collagenases, which are part of the large family of matrix metalloproteinases. For type I collagen, the cleavage site is specific, generating threequarter and one-quarter length fragments. These fragments are further degraded by their matrix proteinases, as illustrated in Figure 14. Therefore, it is mandatory to blend collagen with other materials to augment the mechanical properties of collagen-based scaffolds.

**Figure 14.** Process of collagen breakdown with the presence of a physiologic collagenase enzyme [100].
