**3. Applications of pectin in TE**

Pectin-based formulations have been processed through different fabrication approaches into scaffolds with various shapes for different applications. In particular, pectin has been mainly used for the production of 2D films for wound healing, and 3D scaffolds for tissue regeneration. **Figure 2** provides a graphical overview of the main applications of pectin in TE.

#### **3.1 2D patches for tissue regeneration**

One of the applications of pectin-based formulations is the preparation of 2D hydrogel patches for the treatment of wounds. These patches provide mechanical support to cells during the process of new tissue formation, and an antibacterial barrier preventing eventual infections. Moreover, the hydrophilic pectin molecules in the film can react with the fluids of the wound forming a soft gel. The presence of a gel allows to maintain a moist environment in the wound. This helps to remove or control secretions from the wounded tissue and in turn facilitates the healing process. The regeneration of the damaged tissue can be further promoted by the incorporation of bioactive molecules such as drugs (e.g., antibiotics) and/or growth factors within the pectin patches [21]. The controlled and prolonged release *Pectin-Based Scaffolds for Tissue Engineering Applications DOI: http://dx.doi.org/10.5772/intechopen.101521*

**Figure 2.**

*Illustration of the application of pectin (derived from citrus fruits) for the production of scaffolds for TE applications (created with BioRender.com).*

of these molecules directly in the damaged site can actively contribute to decreasing the risk of infections and accelerating the formation of new tissue. As mentioned in Section 2, pectin is often combined with other biopolymers to enhance its bioactivity and also to modulate the physical properties (e.g., tensile strength) of the final patch.

Pectin-based patches for wound healing reported in the literature so far are principally obtained in the shape of non-porous films and porous membranes, as detailed described in the following Sections 3.1.1 and 3.1.2, respectively.

#### *3.1.1 Pectin-based films*

Pectin-based films are generally 2D, non-porous and flexible substrates able to retain large volumes of water within their matrix. One of the approaches used to produce these films is the so-called 'solvent casting'. In this approach, a pectinbased solution is initially poured into a mold, and the solvent is subsequently let to evaporate leaving a 2D non-porous film (**Figure 3**).

**Figure 3.** *Illustration of the solvent casting approach (created with BioRender.com).*

#### *Pectins - The New-Old Polysaccharides*

Pectin-based patches produced with this approach support cell adhesion and proliferation and accelerate the processes occurring during the formation of new tissue [27–30]. Moreover, films with high toughness and stretchability can be produced with solvent casting, and these can be potentially used as pectin-based patches for load-bearing tissues (e.g., cartilage, tendon) [28]. In addition, pectinbased patches for a controlled drug into the targeted tissue were also produced by incorporating drugs in the pectin matrix [30, 31].

## *3.1.2 Pectin nanoporous membranes*

Nanoporous membranes based on pectin have been mainly obtained through electrospinning. This approach allows to produce highly porous and flexible patches starting from pectin-based/polymer solutions subjected to an external electric field. A standard electrospinning apparatus is illustrated in **Figure 4**. It generally consists of (i) a syringe pump containing the polymer solution, (ii) a metallic needle through which the polymer solution is ejected, (iii) a high voltage power supply (in the range of tens of kVolts), and (iv) a grounded collector (usually a metal plate). When a drop of the polymer solution is extruded through the needle, the high electric forces in the space between the needle and the collector induce its stretching and the formation of fibers from a few nanometers to microns in diameters [32]. These fibers are therefore deposited and collected on the collector forming a nonwoven fibrous membrane after complete evaporation of the solvent (**Figure 4**).

Pectin-based patches obtained by this approach show several advantageous properties for TE applications. The random organization of electrospun pectin fibers together with the hydrogel nature of pectin enables to mimic the nanoscale organization of the native extracellular matrix. Furthermore, the high porosity and high surface-to-volume ratio typical of electrospun patches promote cell migration and nutrient diffusion within the scaffold, which is beneficial for the process of new tissue formation [33]. Nevertheless, it is quite challenging to produce electrospun structures from pristine pectin due to some intrinsic molecular properties of pectin (such as insufficient chain entanglement) that disable the fiber formation [34]. Thus, to improve its electrospinning ability, pectin is often chemically modified [35, 36] and/or combined with other biodegradable biopolymers such as poly(ethylene oxide) [34], polyhydroxybutyrate [37] that work as carrier polymer to induce the formation of stable fibers.

#### **Figure 4.**

*Illustration of an electrospinning setup with a magnification of the electrospun nanofibers on the collector (image obtained with scanning electron microscopy).*

Pectin-based nano-fibers find application for the preparation of films/structures that can be potentially used as patches for wound healing of soft tissues [35–37] (e.g., vascular tissue [35], retinal tissue [37]). In addition, drugs (such as antibiotics [38, 39]) and particles (such as argentum ions for antibacterial purposes [38]) can be successfully loaded in these structures obtaining patches for a local and controlled release of drugs directly into the wound.
