**6. Challenges of 3D printing in tissue engineering**

Although tissue engineering emerged with this glory for a few decades, the initial attempts took way long [104], whereas 3D printing of complex biomaterials is a promising means of scaffold designing.

There are different types of 3D printers: laser-, inkjet-, and extrusion-based. However, inkjet-based is more popular in tissue engineering, where cells or biomaterials are incorporated into the substrate, as per digitally set instruction, to recreate a functional organ or tissue. Multiple printheads can be used in the case of organs/ tissue containing different types of cells. However, there are several challenges to address while designing a 3D printed engineered tissue [105].

#### **6.1 Materials**

#### *6.1.1 Choice and processability of materials*

The form of material input is important for this specialized process of 3D printing. Hence, it is important to think through before choosing a material, whether it is compatible to form a filament or powder or pellet or solution, that is required for that process. Another important feature to be considered while choosing the material is the expected mechanical strength of the scaffold and their biocompatibility and biodegradability.

#### *6.1.2 Rate of biodegradation*

The sole intent of engineered tissue is to replace and regenerate damaged tissue or organ. To comply with this requirement, the scaffold material of the transplanted tissue should be subject to remodeling and absorption. They should be able to degrade in equal or similar pace with the regeneration of extracellular matrix and differentiation of cells. This phenomenon depends on several factors, including hydrophilicity of the scaffold, surface area, porosity, degree of crystallinity, presence or absence of certain enzymes, etc. The most critical part here is harmonization in these factors, so that the degradation of biomaterial and stress release to the surrounding tissue is well synchronized, to ensure healing of the damaged tissue.

#### *6.1.3 Biodegradation of product*

Biodegradation rate affects the cell viability and mobility, despite the general concept of this biodegradation being non-cytotoxic. The study finds that the fast degradation of the polymer may affect the cells negatively due to the formation of acidic byproduct. However, more research is required to support these data and to develop the degradation profile of the materials.

#### *6.1.4 Mechanical strength*

Cells are described to be sensitive toward the mechanical strength of the polymer scaffold. Rigid and non-flexible material may hinder the cytoskeleton

**199**

evenly.

*3D Printed Bioscaffolds for Developing Tissue-Engineered Constructs*

assembly, cell organization, and receptor recruitment into "focal adhesion plaques," which is crucial for cell signaling and anchoring. On the other hand, highly pliable material may not be able to provide the mechanical strength for anchoring or

Different tissues require different porosities for the optimum effect. However, little knowledge is available. A general range of pore size is suggested to be considered for any type of cell, based on observations, rather than the established theory

A study by Yin et al. describes that the microgrooves on the scaffold surface directly affect the cardiac function and susceptibility to arrhythmias [106]. This indicates the importance of the scaffold surface microenvironment, which posi-

It is stated that surface roughness may enhance adhesion between cell and extracellular matrix. At the same time, too rough surface of the scaffold may exhaust the cell adhesion capability. On the other side, if the scaffold material is too sharp, the cells may get damaged. However, choosing a smooth surfaced scaffold material may require consideration of further modification or coating, as this feature does not

Small and simpler organ printing has been successful, without much difficulty. However, it is not simple when comes to bigger and complex organ, due to difficulty in vascularization. Small tissues are avascular, and most of the time, aneural, alymphatic, and thin or hollow. They can receive nutrition from host vasculature. But when the transplanted tissue is thicker than 150–200 μm, oxygen cannot be diffused from host tissue to it. As such, to create a functional bigger and complex tissue or organ, an integrated vascular system is to be created, which

The homogenous distribution of the cells throughout the scaffold is important for the effectivity of the tissue. The conventional usage of Petri dish may not be adequate to ensure the uniform seeding of these cells. The bioreactor technology can influence a successful cell seeding, throughout the depth of the scaffold,

Despite all the challenges, 3D bioprinting offers great potential and diverse

tively or negatively affects the success of the tissue transplant.

cytoskeleton assembly and thus affecting the cellular function as well.

*DOI: http://dx.doi.org/10.5772/intechopen.92418*

**6.2 Designing the polymer scaffold structure**

of optimum pore size for each cell type.

*6.2.2 Morphology of the polymer scaffold*

*6.2.3 Surface topography*

facilitate cell adhesion.

is still not in place [105].

**6.5 Future prospect of 3D printing**

applications for the medical and healthcare sector.

**6.4 Cell seeding**

**6.3 Vascularization**

*6.2.1 Porosity*

assembly, cell organization, and receptor recruitment into "focal adhesion plaques," which is crucial for cell signaling and anchoring. On the other hand, highly pliable material may not be able to provide the mechanical strength for anchoring or cytoskeleton assembly and thus affecting the cellular function as well.
