## 1 Introduction  
Bone tissue lesions are among the most common injuries of the human body, which affect the quality of millions of people worldwide [1]. It has been estimated that the prevalence of bone lesions requiring treatments will double during a period between 2012 and 2020 due to an aging population, traumas, congenital genetic abnormalities, and obesity [2]. As such, the need for bone replacement increases dramatically worldwide and becomes a key scientific, socio-economic, and clinical challenge. Recently, the use of tissue engineering (TE)-based strategies has appealed greatly for healing the damaged bone tissue. The fundamentals of TE include three principles including cells, biomaterials, and growth factors, which are necessary for generating the regenerated functional tissue [3]. Most of the strategies applied for BTE are based on bone formation through intramembranous ossification (IO), which commonly leads to poor vascularization and limited-area bone regeneration. Therefore, bone regeneration via a cartilage-mediated process similar to endochondral ossification (EO) has recently attracted greater attention in BTE, especially for long bones reconstruction, to overcome the limitations of the IO approach [4; 5]. As one of the main building blocks of TE field, cells have attracted increasing attention for in vitro and in vivo bone regeneration due to their substantial role in the acceleration of the healing process. For example, cells are able to improve the healing process by secreting numerous cytokines including VEGF, HGF, bFGF, and IL-6 [6; 7]. Moreover, cells are involved in the secretion of the extracellular matrix (ECM), which provides necessary physical scaffolding for the cellular constituents as well as initiates essential biochemical and biomechanical cues required for tissue morphogenesis, differentiation, and homeostasis [8]. There are some well-recognized and accepted criteria to use in cells for in vivo bone repair and regeneration including ease availability, abundance, a lack of the induced host immune response, and incorporate the proper potential for osteogenic differentiation [9; 10]. Currently, various types of both differentiated (e.g. osteoblasts) and undifferentiated cells (embryonic, fetal, and adult stem cells) are used for treating damaged bone tissue. It was previously well documented that the nature and commitment of the transplanted cells significantly control the type of ossification in vivo [11; 12; 13]. For example, [PERSON] et al. showed that the activation of an endochondral ossification process happened when they transplanted mesenchymal stem cells (MSCs)-seeded porous ceramic scaffolds in immunocompromised mice, while transplantation of osteoblasts (OB)-seeded scaffolds led to an intramembranous ossification [14]. Appropriate cell types are also used with a \"probing function\" to test the in vitro biocompatibility of biomaterials and scaffolds for possible use in TE approaches. In fact, correct strategies for the selection of implantable constructs for bone healing rely on the initial evaluation of biomaterials using different bone cells, i.e., osteoblasts and osteoclasts [15]. The cell fate in vivo will be determined by many biomaterial-related features, such as surface texture (e.g. micro-roughness and nano-roughness [16; 17]), the size of particles [18], dissolution kinetics, and release of ionic species that may elicit specific biochemical and genetic responses in cells and tissues [19; 20; 21; 22; 23]. It is suggested that the biomedical scientists take measures on the cell source used for BTE strategies to get better outcomes.