Shandong Medicine, Vol. 61, No. 13, 2021
Li Min', Li Dalu
1School of Stomatology, Dalian Medical University, Dalian 116000, China; 2. Jinan Stomatological Hospital
Abstract:Dental implants are the preferred treatment for many edentulous patients to restore the integrity of their dentition, and the lack of alveolar bone mass in the implant area caused by various factors will obviously affect the success rate of implant surgery. Alveolar bone reconstruction bone augmentation surgery can greatly improve the success rate of oral implant surgery and the clinical effect of implant restoration. Different types of bone grafting materials have different effects in increasing the height and width of missing alveolar bone and reconstructing the original structure and function of bone defects. Keywords: Oral implants; Bone augmentation: Bone graft material
doi:10.3969/i.issn.1002-266X.2021.13.029
CLC Number: R783.1 Document Symbol Code: AArticle Number: 1002-266X(2021)13-0100-04
Adequate peri-implant bone mass is the key to long-term stability after implant placement. However, alveolar bone atrophy caused by inflammation, trauma, tumor, alveolar bone resorption after tooth extraction and long-term missing teeth often causes insufficient alveolar bone mass in the implant area, in this case, surgical methods such as 0NLAY bone grafting, alveolar ridge splitting, stretch osteogenesis, GBR and other surgical methods are required to cooperate with bone grafting materials for bone augmentation to restore the bone mass in the implant area and enable the implant to be implanted at the ideal implant site. The characteristics of bone grafting materials in osteogenesis include osteoconductivity, osteoinduction and bone regeneration, and the ideal bone grafting materials should have the above three characteristics at the same time. The research progress is summarized as follows
1 Autologous bone grafting material
Autologous bone has good osteoconductivity, osteinduction and bone regeneration, which is the gold standard of bone grafting materials, and it is easy to survive after transplantation, without immune rejection, and can shorten the osteogenic cycle. Autologous bone is often used in clinical practice in the form of lumps or granules. Compared with lumpy bone, granular bone chips can release bone-derived growth factors more quickly, and the effect is better in the reconstruction of small and medium-sized bone defects, but its acquisition is relatively limited, and it is easily affected by external forces, and the absorption rate is faster. The choice of autologous bone retrieval site is mainly affected by the amount of bone required by the bone graft site and the biological properties of the donor bone area, and bone is often taken from the patient's head and face, limbs or mouth.
The amount of bone donated outside the mouth, such as the skull, tibia, ilium, etc., is sufficient and can be used for the reconstruction of a large range of bone defects. However, extraoral bone extraction needs to be performed under general anesthesia, which is long, costly, and difficult, and increases the risk of intraoperative and postoperative complications. For example, there is a risk of dural tear, deformity, and residual scar alopecia after bone extraction, among which hair loss is the most common; Bone extraction from the anterior superior iliac spine may lead to sensory nerve damage and gait instability, and in the case of large grafted bone fragments, bone necrosis and resorption may occur due to ischemia; Compared to iliac cancellous bone grafting, the tibia has a higher fat component, and complications such as long-term pain, gait disturbance, wound infection, hematoma, and fracture may occur after surgery.
Intraoral bone extraction can be performed under local anesthesia, the operation time is shorter, postoperative complications are few, and there is no facial scarring, which is more acceptable to patients. In the case that the amount of bone donor can meet the requirements of repair, intraoral bone extraction is preferred. Intraoral bone is often taken in the mandible, the mandibular tuberosity, the mandibular ascending artery, and the posterior molars. The mandible is dominated by cortical bone, which has a high bone density, slower resorption after transplantation, and a short healing period. However, mandible-derived autologous bone fragments have poor revascularization and regeneration, and osseointegration after transplantation may be risky. The chin is located in the anterior part of the mandible, which has a good surgical field and sufficient bone mass to produce rectangular bone with a small amount of cancellous bone. The most common complications after bone retrieval are paresthesia in the frontal skin, numbness of the lower lip, pulp damage of the lower anterior teeth, and depression of the bone extraction area, which may affect the appearance of the chin. In order to effectively avoid the above risks, it is necessary to conduct a detailed examination and evaluation before surgery, and strictly control the scope of bone collection during surgery. Compared with the mandible, the maxillary tubercle area is mainly cancellous bone, which can be used to produce bone chips or cancellous bone fragments, and the possibility of sensory nerve damage during surgery is less, and the postoperative swelling is less than that of mandibular bone retrieval, but the ability to resist resorption is worse than that of mandibular bone pieces.
2 Natural tooth-derived bone grafting materials
The tissue structure of natural dentin is similar to that of bone tissue, and the organic components are mainly type I collagen, and the inorganic components are mainly hydroxyapatite (HA), and also contain non-collagen and a variety of biological factors. Collagen can be loaded with a variety of growth factors to promote bone formation and mineralization. After the dentin matrix is grafted into the human bone defect area, it can also be used as a reservoir to slowly release non-collagen such as BMP, regulate bone resorption and bone regeneration, and increase and induce osteogenesis. Therefore, dentin has better osteoconductivity and osteoinduction than scaffold materials containing collagen or HA alone, and is more suitable for bone tissue engineering. At present, the forms of dentin mainly include deproteinized dentin and demineralized dentin. The deproteinization treatment can increase the porosity of dentin by about 20% compared with the original one, and effectively play the role of calcium phosphate such as HA as a scaffold to promote regeneration. The demineralized dentin matrix has both collagen and HA, and the dentinal tubules are widened, which is conducive to the release of various growth factors. Demineralized dentin is more easily degraded, and the mechanical properties of the dentin matrix will be reduced by the above treatments.
In recent years, commercialized dentin materials have been used in clinical bone augmentation surgeries such as maxillary sinus lift and GBR alveolar ridge site preservation surgery. JUN et al.4 found that the osteogenesis rate, new bone density, and amount of residual bone graft material in maxillary sinus floor augmentation were similar to those of Bio-0ss bone meal, but the bone thickness was higher. JOSHI applied AutoBT to alveolar ridge site preservation and found that all implants had good initial stability and that the bone resorption rate after autologous dentin transplantation was lower than that of artificial bone.
3 Allogeneic bone graft material
Allogeneic bone is derived from the healthy bone tissue of other individuals in the same population, and is often stored in bone banks for use in the form of fresh frozen bone (FFB), demineralized bone matrix (DBM), lyophilized bone (FDBA), or demineralized lyophilized bone (DFDBA). After demineralization or lyophilization, allogeneic bone retains the three-dimensional structure and BMP of natural bone tissue, and has good cytocompatibility, bone conduction and osteoinduction, but lacks osteogenic characteristics due to the lack of viable cells. Although allogeneic bone has higher mechanical stability than other types of allogeneic bone, it still has the risk of disease transmission and immune rejection, and is no longer used in clinical practice.
3.1 DBM DBM is a bone grafting material obtained by chemical methods after decalcification and degreasing of allogeneic bone, and the original trabecular bone structure remains unchanged and the pores increase, similar to cancellous bone. KIM et al. found that the osteogenic processes of DBM and autologous bone were similar. In maxillary sinus floor lifting, DBM has better osteogenic capacity compared to other xenograft materials that only have osteogeneity. DBM can also rapidly reconstruct blood vessels and is able to act as a carrier for autologous bone marrow. The osteogenic ability and osteogenic quality of DBM combined with autologous bone marrow are better than those of DBM alone. The antigenic structure of the bone surface is destroyed after DBM is treated and does not cause a local foreign body reaction, but it does not provide structural stability and is therefore only used in a structurally stable environment
3.2 FDBA After freeze-drying in a cryogenic freezer, FDBA retains BMP, collagen and the original three-dimensional structure and reduces its antigenicity, which is conducive to cell adhesion, proliferation and osteogenic differentiation. However, after freeze-drying in a cryogenic freezer, its mechanical properties will also be reduced, and it can be used in combination with barrier membranes. FEUILLE ET AL.: THE TREATMENT OF LOCAL ALVEOLAR RIDGE DEFECTS WITH MINERALIZED FDBA COMBINED WITH TITANIUM-REINFORCED POLYTETRAFLUOROETHYLENE BARRIER MEMBRANE SHOWED THAT THE AVERAGE ALVEOLAR RIDGE WIDTH INCREASED BY ABOUT 3.2 MM, AND THE AVERAGE NEW BONE FORMATION RATE WAS 47.6%.
3.3 DFDBA After freeze-drying and demineralization, the BMP in the matrix is exposed, which makes it have good bone conduction and osteoinduction. In the clinical application of periodontal bone grafting surgery, DFDBA has been proven to be a safe and effective bone grafting material. After periodontal flap surgery, implantation of DFDBA in the subosseous pocket site can provide more increased attachment and filling of bone defects. DFDBA can be used in combination with the patient's own bone marrow to promote new bone formation. At the same time, the combination of DFD-BA and platelet-rich plasma can also improve its osteogenic effect." However, DFBDA is easily absorbed after implantation into the maxillary sinus, and the possibility of maxillary sinus regasification increases after seed loading, so some scholars believe that DFDBA is not suitable for maxillary sinus floor lifting
Clinically, autologous bone can be combined with allogeneic bone, and the mixed bone graft material can combine the advantages of the two to improve osteogenic efficiency, shorten osteogenesis time, reduce bone resorption, and reduce the required autologous volume. Fresh autologous bone fragments and blood can also be mixed 1:1 with allogeneic bone graft material, or allogeneic bone can be combined with autologous bone marrow.
4 Heterogeneous bone material
Xenogeneic bone graft materials are bone graft materials from different species: bone substrates mainly from animals (such as cattle, pigs, etc.), calcified coral substrates, etc., with a wide range of sources and low prices. At present, the commonly used xenotransplantation material in clinical practice is deproteinized calf bone (DBBM). DBBM is a bone conduction bone graft material that can resist bone resorption after implantation and is a good scaffold material. Bio-0ss bone meal is the most representative commercial product of DBBM. The three-dimensional structure of Bio-0ss bone meal is similar to that of human cancellous bone, and has good mechanical properties, osteoconductivity and biocompatibility, which can provide a stable osteogenic environment. After grafting the bone defect area, it can be directly guided into bone formation around the bone graft material to form a new bone structure in which bone meal particles are fused with new bone0, and the site preservation after tooth extraction can be obtained by applying Bio-0ss bone powder. JENSEN et al. used Bio-0ss and its combination with autologous bone to lift the maxillary solid bottom, and found that the stability of the bone graft material after grafting the human bone defect area was directly proportional to the proportion of Bio-0ss. Because granular bone meal is susceptible to deformation and displacement under the influence of external forces, it is not easy to maintain the shape after bone grafting, so it can be used in combination with a barrier membrane that can maintain space in clinical practice. The combination of Bio-0ss and biofilm can significantly inhibit the horizontal and multiplication of bone resorption in alveolar bone and promote the formation of new bone.
5. Synthetic bone grafting materials
5.1 Bioceramics The main component of bioceramics is calcium phosphate (CP), which is a synthetic scaffold material, easy to produce and preserve, non-immunogenic, with good biocompatibility and osteoconductivity, but without osteogenesis or osteogenic induction. At present, commonly used bioceramic materials include tricalcium phosphate (TCP), hydroxyapatite (HA) and biphasic calcium phosphate (BCP). The Ca0:P0. ratio of TCP ceramic material is 3:1, which has the best biocompatibility, good osteoconductivity and porosity, and can promote the vascularization of regenerated tissues, and its degradation rate in vivo is faster than that of HA. B-tricalcium phosphate (B-TCP) is a commonly used TCP ceramic material, which has been proven to be used for bone defect repair and maxillary sinus floor lifting. Some scholars have found that the application of B-TCP in maxillary sinus floor lift has a similar osteogenic effect to autologous bone, and is an ideal maxillary sinus bone grafting material. HA is a highly hardened hydroxylated calcium phosphate, and the properties of HA ceramics are almost the same as those of natural HA, which can release calcium and phosphorus ions in living organisms, and is a good scaffold material. However, pure HA has high brittleness, poor bending resistance, and slow degradation after implantation, so the long-term effect of clinical application is not ideal. However, ultrafine hydroxyapatite particles (nHA) have high solubility, and the growth rate of human osteoblasts on the surface of nHA is higher than that of other materials, and it is non-cytotoxic, which has great application potential. BCP is a bioceramic composed of HA and B-TCP, which has good biocompatibility and bone conduction. Among them, BCP with a ratio of HA to B-TCP of 3:7 had the best osteoconductivity. 0HE et al.: It has been confirmed by clinical experiments that BCP has high volumetric stability and can be used for maxillary sinus lifting. However, BCP is not as good as autologous bone and can be used alone or in combination with growth factors.
5.2 In addition to bioceramics, other materials such as calcium phosphate bone cement (CPC) and bioactive glass (BAG) can also be used for bone augmentation. CPC consists of 1 or 2 powder components and an aqueous solution, which can be applied directly after binding or used by a syringe, and the precipitate linked by CP is directly hardened in situ. The mechanical properties and decomposition behavior of CPC depend on the composition of its raw materials and their processing, which can promote osseointegration and resorption through good vascular support. However, CPC has low porosity, slow degradation after implantation, and low bearing capacity, so it is not suitable for high-pressure loading areas and is only suitable for filling bone defects. BAG is a bioactive material based on acidic oxides (e.g., phosphorus pentoxide), silica (also including alumina), and alkalis (e.g., calcium oxide, magnesium oxide, and zinc oxide) that are osteoinducible. When BAG is exposed to interstitial fluid, a silicone-containing gel layer is formed on the surface and a calcium phosphate layer is formed on the top, which can promote osteoblast adsorption and aggregation, forming extracellular matrix mineralization. Some scholars believe that nanoscale BAG has similar properties to HA, but its surface area is larger, and it can also enhance osteoblast adhesion, proliferation and differentiation, and promote periodontal tissue regeneration and bone tissue mineralization. However, at present, the clinical application of CPC and BAG is not as extensive as that of bioceramics to assist osteogenic growth factor
At present, the clinically known growth factors are closely related to bone regeneration, such as bone forming protein (BMP), platelet-rich plasma (PRP), platelet-derived growth factor (PDGF), platelet-rich fibrin (PRF), concentrated growth factor (CGF), etc. These growth factors associated with bone production and remodeling can promote the differentiation of mesenchymal stem cells into osteoblasts and can induce collagen synthesis to regulate bone matrix mineralization.6.1BMPBMP is non-collagen and plays an important regulatory role in bone mineralization, the most commonly used of which is bone-forming protein-2 (BMP-2). BMP-2 can induce the differentiation of pluripotent stem cells into cells, and can also promote the aggregation of endogenous osteocytes to the defective site, and has strong bone induction activity in vitro and in vivo. Some scholars have found that the bone graft material of composite BMP-2 can effectively increase the area and bone density of implant osseointegration, but the rate of new bone formation is slower than that of autologous ilium. Due to the short half-life of protein-based composites, it is difficult to maintain high concentrations, and large doses are often required for multiple uses, which are expensive and often unevenly distributed. Topical application of BMP-2 in excess of physiologic doses during surgery may also lead to serious complications such as extensive soft tissue hematoma and excessive inflammatory response. Therefore, further research is needed on the safe application of BMP in the repair of large-scale bone defects, and BMP has not yet been applied in clinical practice due to ethical issues.
6.2 Platelet-derived growth factors PRP, PDGF, PRF and CGF are all plasma preparations, which are made by centrifuging autologous whole blood and concentrating platelets, all of which have good biodescriptiveness. PRP provides regenerative stimulation, enhances healing and promotes the repair of tissues with low healing potential. The application of PRP at the extraction site after tooth extraction can promote alveolar fossa bone regeneration, and the addition of PRP to the reconstruction of mandibular continuous bone defects can increase bone formation. However, PRP is more effective in promoting the healing of tendons, ligaments, and cartilage than in osteogenesis. PRP preparations are usually activated prior to dosing to release high concentrations of growth factors, and activated PRP can release up to 71% of growth factors within 10 minutes, but there is uncertainty about whether the results of rapid and high-dose delivery of growth factors are ideal. Moreover, studies have shown that PRP has a similar bone regeneration effect with or without PRP activation. Given the limited data, there is no consensus on whether activation is beneficial or not, but activation can alter the nature of PRP and should be considered when comparing the results of clinical studies.
PDGF is mainly produced from platelets, among which recombinant human platelet street growth factor-BB (rhPDCF-BB) is commonly used. rhPDCF-BB can promote angiogenesis, accelerate periodontal tissue regeneration and attachment, and facilitate postoperative wound healing. It was found that the combination of bone graft material and rhPDGF-BB could achieve smooth bone healing. However, the optimal dose, optimal scaffold material and mechanism of action of rhPDGFBB in bone augmentation surgery are not very clear, and further research is needed.
PRF simplifies the preparation process of platelet-rich biomaterials such as PRP, has good biological characteristics, and can better promote osteogenesis when used in combination with bone grafting materials. Bio-0ss combined with PRF for maxillary sinus lift can shorten the healing time, and the osteogenesis effect is better than that of Bio-0ss bone meal alone. AT THE SAME TIME, AGARWAL ET AL. APPLIED PRF ALONE AND IN COMBINATION WITH DFDBA IN THE TREATMENT OF BONE DEFECTS CAUSED BY CHRONIC PERIODONTITIS, AND THE RESULTS SHOWED THAT THE COMBINATION OF PRF AND DFDBA HAS OBVIOUS ADVANTAGES IN THE TREATMENT OF BONE DEFECTS. However, the addition of PRF to B-TCP does not promote new bone formation and may exacerbate the inflammatory response.
CGF contains higher concentrations of growth factors than PRF. MASUKI ET AL. FOUND THAT HIGH-GRADE PLATELET-RICH FIBRIN AND CGF EXTRACTS CONTAINED HIGH LEVELS OF PLATELETS AND PLATELET-DERIVED GROWTH FACTORS, WHICH COULD SIGNIFICANTLY PROMOTE THE PROLIFERATION OF HUMAN PERIOSTEAL CELLS IN VITRO STUDIES, AND COULD BE USED AS A RESERVOIR TO RELEASE GROWTH FACTORS AFTER BEING APPLIED TO BONE DEFECTS. LEI et al.8 found that CCF could stably and continuously release growth factors within 14 days after being applied to the bone defect area, and improve the effect of tissue regeneration in bone defect reconstruction. Some scholars used CGF combined with Bio-0ss to reconstruct the collar bone defect, and it was found that the bone mineral density of the bone defect in the experimental group was higher than that in the Bio-0ss group alone 6 months after surgery. In immediate implantation, the use of CGF combined with Bio-0ss for GBR can effectively improve the clinical treatment effect, inhibit the inflammatory response, and promote bone regeneration. However, the long-term effect of CGF in combination with other materials is not clear.
7. Summary and outlook
At present, bone defect reconstruction can be carried out by using a variety of surgical methods in combination with bone grafting materials. The ideal bone graft substitute should have the advantages of good biocompatibility, bioresorbability, osteoconductive osteoinduction, similar structure to bone, ease of use, and low cost. Considering the different characteristics of bone graft materials from different sources, different kinds of bone graft materials can be mixed to improve the osteogenic performance and stability of bone graft materials. Through clinical application, it has been found that a good osteogenic effect can be obtained by mixing autologous bone chips with Bio-0ss bone meal 1:1 or mixing autologous bone chips, granular allogeneic bone and Bio-0ss bone meal 1:1:1. In addition to bone grafting materials, there are also a variety of growth factors that are used in clinical practice to assist in osteogenesis, but they still have the potential to lead to disease transmission, immune problems, and uncontrolled bone formation. It is believed that with the development of oral implant technology and bone tissue engineering, bone grafting materials with better osteogenic performance and better use schemes will emerge in the future, so that the success rate and long-term effect of oral implant surgery will be more ideal.
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