## 1 Introduction  
When compared to other human body tissues, bone tissue is a distinctive tissue in terms of regeneration and self-repair. However, the process of bone healing might be restricted by a series of factors which may include on-site infections, location of the defect, depth, width, or other individualities of trauma, disease, immune system performance, or patient particularities. According to recent estimations, the incidence of bone fractures is constantly growing, while the rate of healing failure is more than 10%, especially in patients that suffer from age-related disorders, genetic diseases, malformations, or even bone tissue diseases (e.g., osteoporosis, rheumatoid arthritis) because all of these factors are restricting the self-healing ability of the tissue [1; 2]. For instance, the International Osteoporosis foundation stated that every 3 s a fracture caused by osteoporosis occurs worldwide, with a total of around 9 million annually. The total number of patients affected by this disease was estimated to be around 75 million in Europe, United States of America, and Japan. Moreover, there is a high disability associated with osteoporosis, having a major impact on the economic sector of each country as less patients are able to work or continue with their daily activities [3,4]. The treatments available on the market are based on medication which aims to decrease the risk of fracture, including biophosphonates (risedronate, zoledronic acid), teriparatide, romozumab, denosumab, or raloxifene. However, the risk of fracture and massive bone loss is still high, the osseointegration of an implant or prosthesis is difficult, and the native regeneration processes are slow and difficult [5]. These issues are also applicable in other bone diseases, for example, in patients with arthritis, where the incidence is one in five. Arthritis affects the joints by damaging the cartilage causing bones to start to press on each other, leading to bone loss, fractures, and disability [6]. Small bone injuries are usually stable and benefit from spontaneous native healing without the need for surgery. However, injuries correlated with bone loss lead to inadequate alignment of bone structures and present high instability, therefore the need for surgical intervention becomes a must. Bone fracture healing occurs by numerous events starting with hematoma formation, followed by inflammation and cartilaginous structure creation, angiogenesis, and mineralization. This process is complicated in large bone defects and, when other pathologies are present, complete fracture healing is almost impossible to achieve [7]. In such cases, bone grafts are used to fill the defects caused and speed up the healing process. The use of a proper bone graft is correlated with multiple aspects, including defect nature and size, graft characteristics (size or shape), biomechanical performance, physiological conditions, handling, manufacturing process, production costs, or ethical principles [8]. Three main classes of bone grafts can be distinguished: allografts, xenografts, and autografts [9]. While autografts present important osteogenic characteristics with a key role in bone healing and remodeling processes and represent the 'gold standard', their use has been associated with a variety of drawbacks, such as donor site morbidity, injuries at the harvesting site, or severe pain. On the other hand, xenografts and allografts present good osteoinduction and osteoconduction, but both of them present a deficient osteogenic performance. Moreover, xenografts and allografts showed high rejection rates and increased risk in disease transmission [10]. Therefore, tissue engineering strategies based on the use of biomaterials as scaffolds for filling bone defects have attracted a great interest.