In addition to autologous bone, several other materials are used in dentistry and oral and maxillofacial surgeries to replace or repair bone defects. The selection of the best material depends on several factors, including tissue viability, size, shape, and defect volume ^[1][2][1,2].

Bone grafting is a common procedure in dental medicine used in various situations. Some common clinical dental medical procedures in which bone grafts are needed are dental implants, ridge augmentation, sinus lift, socket preservation, and periodontal surgery ^{[3][4][5][6][7][8]}[3,4,5,6,7,8]. Dental implants are artificial tooth roots that are placed into the jawbone to support dental prosthetics, such as crowns, bridges, or dentures. Sufficient jawbone volume and density are crucial for successful implant placement. If a patient lacks adequate bone in the implant site, a bone graft may be necessary to augment the area and provide a solid foundation for the implant [4]. When a tooth is extracted, the surrounding bone may shrink or resorb over time. Ridge augmentation is a procedure in which bone grafts are used to rebuild and restore the height and width of the jawbone ridge. This procedure may be performed to create a suitable foundation for dental implants or to improve the appearance of the gumline [8]. The maxillary sinuses are air-filled spaces located above the upper jawbone. If the upper jawbone has insufficient height or volume to support dental implants in the posterior region, a sinus lift procedure may be required. In this procedure, the sinus membrane is lifted, and bone graft material is placed between the sinus membrane and the jawbone to increase the bone height [6]. When a tooth is extracted, socket preservation techniques can be used to minimize bone loss in the empty socket and preserve the bone volume for future dental implant placement. A bone graft is typically placed in the socket after the tooth extraction to fill the void and maintain the bone structure [7]. In some cases of advanced periodontal disease, bone loss can occur around the teeth, leading to tooth mobility and eventual tooth loss. Bone grafts may be used in periodontal surgery to regenerate and restore the lost bone around the affected teeth, promoting stability and preventing further tooth loss [3].

Under healthy conditions, small bone defects manage to regenerate spontaneously; however, extensive bone defects or loss, pathological fractures, and bone infection due to periodontal problems or systemic diseases can influence bone healing and regeneration, requiring surgical intervention and the choice of a substitute bone ^[1][9][10][1,9,10].

Extensive bone defects are usually treated with autologous bone taken from the iliac crest or the calvaria. Autologous bone contains osteogenic cells capable of synthesizing new bone and its structure serves as a scaffold, making this procedure the gold standard of bone grafting. However, this procedure has some disadvantages ^[1][2][11][1,2,11].

To avoid complications, other bone substitutes are often used in medium and small-size defects and include allografts (human bone other than the patient’s own (e.g., extracted from cadavers)), xenografts (bone from animals other than human species), and synthetic materials with osteoconductive properties that can be reabsorbed by the body, releasing substances that contribute to the formation of new bone (e.g., ceramics, bioactive glasses, polymers, synthetic hydroxyapatite (HA)) ^[12][13][12,13].

Bone grafts should have specific requirements in order to be used and have optimal performance: (i) unlimited supply without compromising the donor area, (ii) promote osteogenesis, (iii) no host immune response, (iv) rapid revascularization, (v) stimulate osteoinduction, (vi) promote osteoconduction, and (vii) be completely replaced with bone in quantity and quality similar to that of the host ^[2][14][15][2,14,15].

Osteoinduction is defined as the process by which osteogenesis (i.e., new bone formation from osteocompetent cells in connective tissue or cartilage) is induced. Osteoconduction is defined as the process of bony ingrowth from local osseous tissue onto surfaces. Osteogenic materials are defined as those which contain living cells and are capable of differentiation into bone [16].

2. Bone Grafts in Dental Medicine

There are several materials available for bone grafts and the selection of the ideal material depends on a number of factors, such as material availability, defect size, size, shape and volume of the graft, biomechanics, handling, cost, ethical issues, biological characteristics, and associated complications [2]. Among the available options in the area of bone regeneration, the gold standard remains autogenous bone, due to its osteoinductive and osteogenic capabilities. All other materials (allograft, xenograft, and synthetic biomaterials) have limitations, which must be taken into account, depending on their use [2]. These categories will be briefly described below.

2.1. Autografts

Autografts are the gold standard materials for bone grafts in the field of medicine and dentistry due to the fact that these materials have many of the requirements considered optimal for a bone graft as they are biocompatible, non-toxic, osteogenic, osteoinductive, and osteoconductive ^[17][18][17,18]. These advantages are fundamental for fast and efficient bone regeneration, mainly in defects considered of critical size (>5 mm), since the vascularization is reduced in the centre of these defects ^[17][18][17,18]. Healing time is also dependent on the material used, with autologous bone being the most rapidly vascularized and, therefore, the most osteogenic of all materials currently available ^[19][20][19,20]. It is important to emphasize that the combination of cortical and medullary bone is one of the most advantageous in the area of bone regeneration, since it unites two important characteristics: the support and mechanical resistance of the cortical bone and the osteogenic function of the medullary bone [20]. However, this procedure has some disadvantages, namely, the uncertain prognosis and surgery at the bone removal site as well as the sequelae that may occur in the process, such as the risk of infections. Additionally, the quantity and quality of the donor’s bone may be insufficient, due to age-related problems or disorders that may affect the patient’s medical condition (e.g., metabolic diseases, osteoporosis, and diabetes) ^[1][2][11][1,2,11]. In dentistry, this type of procedure is only used in critical cases, such as jaw reconstruction, congenital bone defects, tumours, and bone defects larger than 5 mm, due to the limited amount of intraoral bone and the need for an extra procedure to remove bone from another area, requiring hospitalization, a hospital environment, and a multidisciplinary team [21]. With the need for an extra surgery to remove autogenous bone, the risks inherent to any surgery increase: pain, infection, scars, in addition to extra costs with hospitalization and a multidisciplinary team ^[21][22][23][21,22,23]. Autologous bone, although still considered the best option, has been replaced over the years by other materials, with the aim of reducing patient morbidity, treatment costs, and surgical time, as well as the postoperative period.

2.2. Allografts

Allografts are derived from individuals within the same species. After extensive screening, these grafts are carefully selected, processed, and preserved in bone banks. Allografts can originate from living donors or cadaveric bone material after being processed to eliminate immune responses and prevent transmitting infectious diseases. These grafts are available in different shapes and sizes, including cortical, cancellous, or cortico-cancellous grafts [24]. Allografts, despite being used with some frequency in regenerative treatments in some areas of medicine, these materials are not one of the first-choice materials in dentistry. There is still some controversy regarding their osteoinductivity, as well as their risk of immune rejection, blood incompatibility, and disease transmission ^[2][12][18][2,12,18]. Allogeneic materials are considered a source of type I collagen and morphogenetic proteins (BMPs), which give them osteoinductive capabilities. However, although they originate from the human species, they have different genetic compositions, which raises controversy about immunological rejection, blood compatibility, and transmission of diseases or tumour cells ^[2][12][18][2,12,18]. Considered osteoinductive and osteoconductive, they do not have osteogenic properties, and their processing ends up reducing their biological and mechanical characteristics ^[2][12][18][2,12,18]. Although with some advantages similar to autogenous bone and greater availability, allogeneic materials have a high processing cost, in addition to the already mentioned disadvantages regarding disease transmission, immunological rejection, and religious issues ^[2][12][18][2,12,18].

2.3. Xenografts

Materials of animal origin, xenografts, are widely used in dentistry, being well-documented materials studied for more than three decades [24]. Their osteoconductivity comes from their inorganic structure, composed mainly of HA, obtained through the removal of all organic components [25]. Xenografts can be of the most diverse origins, the most used being those of bovine and porcine origin; however, other origins include horses, coral exoskeleton, and eggshells, among others ^{[26][27][28][29]}[26,27,28,29]. One of the advantages of xenogeneic materials is the similarity of their chemical composition to human bone, with a calcium/phosphate ratio of 1.67, identical to that of human bone [30]. Their disadvantage comes from ethical, religious, and health issues, such as the risk of disease transmission ^[2][31][2,31]. Xenografts are the materials most used by dentists. Their effectiveness is very well documented in several comparative studies with other materials, mainly with autologous bone ^{[2][20][32][33]}[2,20,32,33]. One of the xenogeneic materials on which there are more publications and which is also well known by dentists is Bio-Oss^®. Bio-Oss^® is obtained from bovine HA; one of its main characteristics is its similarity in chemical composition with human HA. Its calcium/phosphate ratio of 1.67 is identical to that found in human bone [18]. Materials from other sources, such as equine, porcine, coral exoskeletons, and even eggshells, have been studied and commercialized ^{[26][27][28][29][34][35][36][37][38]}[26,27,28,29,34,35,36,37,38]. Each material has specific characteristics, but in general, among the advantages of these materials, it is possible to mention their low cost, great availability, and osteoconduction [2]. Consisting entirely of inorganic bone, with no organic or cellular content, some materials, such as Bio-Oss^®, are also considered osteoinductive, information that conflicts with some authors, who consider that osteoinduction occurs when there is cellular material, such as morphogenic proteins, growth factors, or some living material in the composition of the bone graft ^[2][18][2,18]. Due to this osteoinductive characteristic, materials of animal origin have been the subject of controversies and discussions about their use in humans. As a natural material, it is possible that they retain some of their original characteristics after processing, such as some cellular activity that gives them the osteoinductive characteristic ^[31][39][31,39]. Although companies that market bones of xenogeneic origin guarantee that their products are completely free of any organic material, some plastic surgeons have detected proteins, such as collagen, in Bio-Oss^® after orthognathic surgery [40]. In another study, reaction to foreign bodies, which consisted of multinucleated cells encapsulated within inorganic bovine bone particles, was reported after histological analysis [25]. These findings contribute to the controversy about the transmission of diseases that can occur when these materials are used. As sporadic as these cases may be, it is important to inform the patient about this risk and alternatives. If there is no organic component in xenogeneic materials, their osteoinductive capabilities are questionable and, although many studies confirm their osseointegration characteristics, other materials have been the subject of studies, in order to overcome the ethical and religious issues of xenogeneic materials, as well as to improve the manipulation capabilities, to facilitate the procedure for doctors and dentists ^{[20][28][30][39][41][42][43][44][45][46]}[20,28,30,39,41,42,43,44,45,46]. In addition to the issues mentioned above, these materials require experienced handling. As they are particulate materials, they require the use of a membrane to keep the static particles at the defect site and prevent the connective tissue from invading the area that must be remodelled, which makes the procedure more complicated ^[22][29][22,29].

2.4. Synthetic Materials

The role of synthetic bone materials is to promote bone regeneration. Synthetic materials have several advantages concerning the surgical method necessary for obtaining autogenous material: biocompatibility, osteoconduction, injectability, moldability, easy manipulation, minimally invasive procedure, scar reduction (since only the affected area is surgically treated and only one surgery is required), in addition to the decreased risk of infection and other complications ^[47][48][49][47,48,49]. Another advantage is their wide availability, since the material can be easily manufactured in scale, unlike autogenous, allogeneic, or xenogeneic materials. The growing demand for materials for bone reconstruction has stimulated research in the area of biomaterials, in order to supply the scarce source of autogenous and allogeneic bone available [14]. Several bioceramic materials have been developed as an alternative, and several studies—both experimental and clinical—have demonstrated the osteoconductive properties (materials that facilitate infiltration through the bone surrounding the defect) of these materials when used for medium and small bone defects, increasing the bone crest for implant placement, bone defects due to periodontal disease, and maxillary sinus elevation ^{[43][50][51][52][53]}[43,50,51,52,53]. Within the group of ceramics, materials based on calcium phosphate are extensively studied and frequently used as bone grafts due to their compositional similarity with natural bone, with their HA demonstrating excellent biocompatibility. In addition to the granular form, these materials can be manipulated in the form of a paste, which reduces application time and, mainly, improves moldability to the defect ^{[47][50][54][55]}[47,50,54,55]. The use of calcium phosphates for larger defects is restricted due to their lack of osteoinductivity; therefore, there are several studies in order to meet this need [56]. It is important to emphasize that synthetic biomaterials do not have osteoinductive properties (the potential to induce bone formation), considered ideal for the formation of new bone. For this reason, the use of these materials still brings some disadvantages when used in bone defects of critical size, which encourages constant research and the inclusion of other components in an attempt to improve their performance. Other materials can be incorporated into scaffolds of synthetic or xenogeneic origin with the aim of improving their osteogenic properties. Growth factors, cellular content, autogenous bone, and therapeutic elements are some of the materials studied and incorporated into these materials with the aim of increasing biological performance and improving the quantity and quality of new bone ^{[2][57][58][59][60]}[2,57,58,59,60]. This area of study, called tissue bioengineering, is based on key elements, which form the triad: (i) scaffold or carrier material; (ii) biological components (growth factors, drugs); (iii) cells [61].