## 1 Introduction  
Bone grafts offer a mechanical support and a biological function in the treatment of several pathologies, among these high-grade open fractures with bone loss, high-energy trauma, non-union or delayed union, resection of bone tumors, infections requiring extensive bone debridement, and secondary bone defects [1]. Opinions diverge as to the most appropriate bone replacement treatment, when considered from both a clinical and an economic perspective. There is a paucity of clinical evidence and controlled studies comparing different techniques to inform strategies and treatments for critical-sized bone defects. Currenttherapeutic approaches include distraction osteogenesis, first reported by [PERSON] in the 1950s [2], as well as [PERSON]'s more recently developed induced membrane technique [3]. Furthermore, the use of bone grafts--autografts, allografts, xenografts, and synthetic grafts--has been widely communicated. Autogenous cancellous bone graft possesses the properties of osteoinduction, osteoconduction, and osteogenesis, making it the current gold standard of treatment for the management of bone defects. Additionally, it is non-immunogenic and does not carry the risk of transmissible infection [4; 5]. However, the morbidity associated with harvesting the amount of graft required to fill the defect is substantial [6; 7; 8]. In orthopedic surgery, there are situations where synthetic bone substitutes have the same clinical results as autografts, but with the advantage that they do not consume surgical time and are not limited in availability. In particular, the development of bone grafts of natural origin obtained from non-human species has received much attention in recent decades. Xenografts are mainly derived from bovine, porcine, equine, and marine sources. These bone grafts can provide structural support and osteoconduction; however, osteogenesis and osteoinduction are not possible. The fabrication process is based on heating and chemical treatments leading to the production of hydroxyapatite (HA) and/or other calcium phosphate compounds. Then, the organic and osteogenic components of the bone are removed, although the potential risk of disease transmission (bovine spongiform encephalopathy) is not completely avoided [9]. Xenografts of bovine origin have given good results in dental and maxillofacial surgeries, but contradictory results have been achieved in orthopedic surgery, in particular foot and ankle surgery [10; 11]. Xenografts obtained from marine sources are of particular interest given the rich biodiversity of ocean organisms with a similar structure to the human bone, which makes them suitable bone graft biomaterials with osteoconductive properties. Corals are among the most studied marine-derived biomaterials. Coral-based biomaterial is mainly calcium carbonate and can be chemically transformed into HA by a hydrothermal conversion to increase the strength of the coral skeletons [12]. Current clinical evidence is limited to well-contained voids in dental and maxillofacial surgery, and to fill bony voids or gaps that do not affect bone stability in limbs and pelvis [13; 14]. In recent years, other marine species have been investigated for use in bone tissue engineering: macro, seashells (foraminifera; bivalve mollus such as oysters and mussels), sponge skeletons, diatom frustules, sea urchin spines, cuttlefish bone, and other fish bones such as tuna [15]. Calcium carbonate predominates in most of these sources, except for certain sponge skeletons namely Demospongiae and Hexactinellida and diatom frustules, which are based on silicon compounds [16]. Marine sources with a calcium phosphate composition are also under investigation. One of these, the subject of this study, is shark tooth from two commercial species, _Isurus oxyrinchus_ and _Prionace glauca_.