## 1 Introduction
Additionally, the socio-economic outcomes together with the long-term results obtained by using currently available treatments for bone-associated conditions have motivated researchers to consider nanotechnology and bone tissue engineering promising ways for developing more efficient and cost-effective solutions [11; 12; 13; 14]. The aim of this review is to offer a view of current state of the art about the use and synthesis of hydroxyapatite particles and their interaction with the physiological media under certain circumstances. The Importance of Bone Remodeling, Osteoinduction, and Mechano-Transduction Phenomenon in Scaffold Design  
In general, tissue engineering is an approach which involves multiple science domains, such as biology, engineering, medicine, chemistry, and physics, so as to create complex structures which encourage and intensify the human body's response to an injury [15]. In bone tissue engineering, the main scope is to restore the native function of the bone tissue in the case of fractures or diseases. One of the most essential components of such structures is represented by scaffolds which are matrices that act as a platform for guiding the cellular response and, consequently, tissue formation. There are numerous considerations which need to be taken into account when developing a scaffold for bone tissue applications including, but not limited to, native bone structure, biomechanics, pore characteristics, mechanical strength, chemical properties, and manufacturing technique [16]. Over the last decades, a variety of techniques have been used with the purpose of developing highly complex bone scaffolds, e.g., solvent casting, 3D printing (additive manufacturing), chemical foaming, and foam-gel [17; 18; 19]. As previously stated, one current challenge of orthopedic implants, prostheses, or other treatments is represented by the high rate of local infections which may lead to serious pain and complications and consequently to a second surgical intervention, amputation, or, in the worst case, the death of the patient. This is a major drawback considering both patient recovery and the economic impact on the healthcare system. Therefore, the development of a strategy which presents dual-functionality is needed. Bone tissue engineering aims to acquire a system which can direct the cellular response in the human body and present antimicrobial properties. Such a system will potentially induce osteoinduction and limit the use of antibiotics after surgery. Thus, the materials chosen for bone scaffolds have a considerable impact on the final system performance [20,21]. The main mechanism that offers the ability of self-regeneration in bones is the bone remodeling process, which is a permanent process based on bone resorption (regulated by osteoclasts) and bone formation (regulated by osteoblasts). However, there are many cells involved in this process (e.g., osteocytes, lining cells) all performing together in a manner which assures a stable equilibrium between resorption and formation [12]. Bone remodeling occurs in five distinct stages (Figure 1), starting with the resting state in which the tissue surface is covered by cells that are not active and followed by the activation stage where two types of stimuli (physical or hormonal) guide the migration pathway of macrophages and monocytes to the remodeling site where they are subjected to osteoclastic differentiation. In the meantime, the third stage is activated and the osteoclasts start to remove both inorganic and organic components of the bone and form a cutting cone in the compact bone and a so called \"Howship's lacuna\" (a cavity in the trabecular bone). This is important because when the cavity reaches a certain dimension and shape in each type of bone the resorption stage stops. The fourth stage is called reversal and it starts when osteoclasts disappear and the cells which migrated in the second stage deposit a substance on the bone surface which is very close in structure to a cement.