**1. Introduction**

There are 206 bones in human bodies and they consisted of 15% of body weight [1]. Bone defects usually occur by trauma, arthritis, fracture, diseases, etc. and large bone defects need extra intervention to regenerate bone structure and functionality [2]. Bone fractures are very common in societies and around 15.3 million bone fractures with 14 million healthcare visits annually in the United States and it expands with the incensement of the elderly population [3]. The bone defects treatment process can be unsuccessful and lead to delays in treatment, non-unions, and malunions. According to the definition of the Food and Drug Administration (FDA), if the treatment lasts more than 9 months, we are faced with non-unions, but in clinical investigations, this can vary from 2 to 12 months [4]. Considering the high prevalence and the importance of the successfulness of the treatment process, scientists are looking for the best treatment method to treat bone injuries, especially large bone injuries. Today common regeneration replacements are autografts and allografts. Although their limitations such as rare tissue supplements, additional surgeon sites, immunological rejection, and disease transferring restricted their usage. Another treatment method is using implants and bone scaffolds. Although the emergence of tissue engineering in the early 1990s has led to a revolution in bone substitutes, we are facing many challenges in this technique, and efforts must continue to optimize replacement with the highest similarity to natural bone and cartilage tissue [5]. Also, the process of treating bone damage is a complex process that includes various factors. Immune cells and mesenchymal stromal cells (MSCs) cells play an effective role in this process and their behavior should be regulated in such a way that the treatment process is carried out well and does not lead to unwanted reactions such as acute inflammations [6]. Considering the importance of scaffold properties used in cell interactions and as a result in the treatment process, scaffold design should be optimized in such a way that it can provide the desired needs of bone tissue [7]. Recently, 3D printing was introduced as a novel scaffold fabrication method to create a complex cell-laden design with a high mimicking capability of natural tissue using various natural and synthetic materials [8]. Efforts continue to design an ideal scaffold, and perhaps an ideal scaffold for cartilage and bone replacement can be designed in the near future.

In this chapter, the process of bone tissue repair and effective parameters are given first. Then, current used treatment methods and materials for bone tissue repair were summarized. In the following, we will mention the methods of making bone scaffolds based on the 3D printing method and discuss various effective aspects of the 3D printing process, such as the printing methods, the desired needs of the bone scaffolds, and model optimization. Then some of the studies that have been done in this field are discussed. It is hoped that this section can be a guide for researchers in the treatment of bone injuries, especially large bone defects.
