**1. Introduction**

Advances in biomaterials are implicated in the huge results as the artificial support matrices penetrate the barrier of all physicochemical properties in clinical tissue implantation, an artifact of regenerative tissue engineering applications. Unlike traditional tissue grafting, the artificial implanting process involves the replacement of any damaged tissues irrespective of age, diseases, and kinds of trauma. Based on the potential requirements, efforts in different fields that include material science, cell biology, medicine, theory and computational studies represent a versatile contribution in regenerative medicine to save thousands of lives. The preliminary idea of tissue engineering is to reconstruct the traditional surgical or mechanical device-related techniques; those though significantly prevented the untimely demises of lives. The time on demand of available organ donors and appropriate complimentary biological environments are implemented in the term 'Tissue Engineering' (TE) in 1933 by Langer and Vacanti [1]. TE is the versatile gift of scientists who have greatly remodeled and mimicked the *in vivo* biological niche through a combination of engineered biomaterials, cells of interest and biochemical factors, which are important factors for tissue development. The manufacture of the implantation of the desired shape is the key factor in TE, which could support

seeding of isolated cells, cell–cell interaction, and its proliferation and migration. The cell adhesion and secretion of extracellular matrixes (ECM) are switched through growth factor-mediated signaling pathways [2]. The growth factors are the class of cytokines, at the basis of cell attachment, proliferation and migration in tissue regeneration, remodeling and other various cellular functions [3, 4]. Epithelial growth factors (EGFs), platelet-derived growth factors (PDGFs), insulin-like growth factors (IGFs), and hematopoietic cell growth factors (HCGFs) are promising types of cytokines that have played a significant role in tissue engineering.

The new generation of biomaterials has revolutionized the fields of regenerative medicine while, the development of 3D architecture could enable us to mimic the ideal *in vivo* tissue organoid*.* Other important parameters of the supporting scaffolds include the porosity, biodegradability, biocompatibility and good carrier of the therapeutic molecules, immobilized onto the matrixes. Due to intrinsic biological characteristics, both synthetic and natural materials have been investigated to formulate the three-dimensional support structure, but the requirements related to microbial resistance, genotoxicity, and mechanical strength remain to be questioned. Collagen, gelatin, hyaluronic acid, alginate, guar gum, chitosan, polyhydroxyalkanoates are the well-known naturally originated, biocompatible and biodegradable polymers, which have emerged as a bio-mimicking matrixes in the development of artificial 3D construct, but their mechanical as well as hydrophilicity limited its unique usages. The drawback is significantly erased by the appearance of biosynthetic technology. In particular, the discovery of carbon compounds such as carbon nanotubes, graphene oxide nanoparticles, etc., has revolutionized the fields of tissue engineering. The additional biocompatibility, antimicrobial activity and mechanical stability of such compounds are considered to fabricate the bioimitating 3D construct. Furthermore, synthetic materials such as poly (lactidecoglycolide) and poly (ethylene glycol) play an important role in the construction of the ideal scaffold [5, 6].

The challenge in tissue regeneration is the seeding of cells. The risk factors such as *in vivo* immune-rejection, viral or microbial contaminations, processing of clean healthy cells are the main obstacles in choosing of the desired cells. Keeping in mind, the allogeneic cells, i.e., cells from a healthy person is considered for the several tissue regeneration systems. A variety of stem cells has been an essential and elementary option for the *in vitro* cell growth in the regeneration of cartilage tissues [7]. Nevertheless, an ideal scaffold with interconnected porous networks, proper mechanically and biologically appropriate engineering should lead to ECM secretion with prominent adhesion, and cell transduction and proliferation are best suited for tissue engineering applications.

This chapter will explore the sources of the 3D polymer construct and its validity in the biological niche, i.e. biocompatibility and cell motility through different growth factors.

#### **2. Why is the 3D construct in tissue regeneration (TE)?**

In tissue engineering, the assessment of cell compatibility is evaluated in a *"in vitro*" model of either 2D or 3D based on the results of optimal support arrays in which cells must continually increase their colonies as the native tissue environment as shown in **Figure 1**. The trafficking of therapeutic delivery in several cases is to get rid of all kinds of forthcoming issues. Therefore, it must circumvent these obstacles by taking into account various facts such as the extracellular matrix density, the nature of the cell-tissue interaction, and the penetration of nano carriers through

*Current Scenario of Regenerative Medicine: Role of Cell, Scaffold and Growth Factor DOI: http://dx.doi.org/10.5772/intechopen.94906*

**Figure 1.** *Schematic comparison of 2D and 3D cell culture model.*

tissue layers, etc. In 2D cell culture, the cells are grown, adhered to flat polystyrene surfaces in a thin monolayer's manner. The proliferation, migration, epigenetic and genetic expressions are varied as compared to *in vivo* tissue regeneration. Cell attachments and motility also constraint within monolayer frames and are exposed to unlimited nutrient sources. The two-dimensional culture is related to an easy and cost-effective process. However, it deprives the study of cell–cell interaction, cellmatrix interaction, cell signaling, and the nature of cell elasticity, which promotes the usefulness of the biological niche, i.e. the 3D construct.

Unlike 2D model, 3D constructs regulate the cell growth and proliferation in heterogeneity similar to *in vivo* tissue as the exposure of growth factors, oxygen, nutrients distributed unevenly in the scaffold or any other 3D construction. The cell morphology as well as the cell polarity is maintained because it greatly controls the cell-signaling, cell topology and various metabolic activities [8, 9]. However, culturing in 3D models is a lengthy and expensive process and is formulated in several ways: 3D spheroid where cells spend their survival time in layers, mimicking the correct cell–cell and cell-matrix interaction as in the environment of native tissue. The identification of biomarkers and the expression of genes that are involved in topological processes as well as the polarity changes of cancer cells are examined in the spheroid models [10]. Furthermore, it is expected that the adherence and proliferation of primary cells follow all the characteristics of *in vivo* tissue processes [11]. The 3D scaffolding systems, made of biodegradable and biocompatible materials, have demonstrated superior cell migration, proliferation through a network of porous 3D microenvironments [12]. In view of the significant advantages, the utility of bio-imitating 3D constructs is however encompassed in the niche of tissue regeneration though; 2D cell culture is still used as a reliable method before initiating the animal studies.
