Full Regeneration of Maxillary Alveolar Bone Using Autogenous Partially Demineralized Dentin Matrix and Particulate Cancellous Bone and Marrow for Implant-Supported Full Arch Rehabilitation

In implant dentistry, bone augmentation is sometimes necessary for ideal dental implant placement because of the lack of sufficient bone volume, as a result of either height and/or width. Autogenous bone is the gold standard for bone graft material because of its superior osteogenic properties.^1,2  It is typically harvested from jaw or iliac bone and is used in either particulate and/or block bone form. Block bone from the iliac crest is often applied for augmentation of relatively large sections of the alveolar ridge. However, patients often experience discomfort during harvest of block bone from the iliac crest, and it is sometimes difficult to carve the bone to fit the shape of the alveolar arch. In contrast, particulate cancellous bone and marrow (PCBM) harvested from the iliac bone is less detrimental and can be easily formed into the shape of the alveolar ridge with molded titanium mesh; moreover, it has higher osteogenic potential than that of cortical block bone from the iliac crest. Although autogenous bone grafting is a reliable procedure for alveolar ridge augmentation, autogenous bone exhibits nearly 50% resorption after the completion of healing,^1,3  especially after PCBM. To prevent this unpredictable resorption, artificial bone substitutes, such as hydroxyapatite or deproteinized bovine bone, have been mixed with autogenous bone such as PCBM^2,4–7 ; however, these graft materials are not incorporated into natural bone turnover and are present for extended periods of time, which may cause infection.

Demineralized dentin matrix (DDM) is reportedly an excellent bone graft material with osteoinductive and osteoconductive properties⁸ ; it has a structure and components similar to those of natural bone, including the presence of bone morphogenetic protein,^9,10  and can be fully involved in host bone remodeling.¹¹  We have previously shown that autogenous partially demineralized dentin matrix (APDDM) has superior properties relative to those of nondemineralized or completely DDM¹² ; we have also reported its clinical application in implant dentistry,¹³  with favorable results in alveolar bone augmentation procedures, such as alveolar ridge augmentation, socket preservation, and sinus floor augmentation. However, the bone defects were relatively small in cases that resulted in successful alveolar bone regeneration by grafting with APDDM alone. In the present case, we presumed that it would be difficult to regenerate large bone defects by grafting with APDDM alone, because of the deficit of graft material volume and the lack of osteogenic activity. Therefore, we planned to regenerate the alveolar bone by grafting with a mixture of APDDM and PCBM, as we expected the 2 graft materials to mutually compensate for each other's disadvantages.

Here, we report a case in which the patient underwent wide-range maxillary alveolar bone and bilateral sinus floor augmentation by grafting with a mixture of APDDM and PCBM, prior to implant-supported full arch rehabilitation.

A 52-year-old Japanese man was referred to the Center for Oral and Maxillofacial Implants at Nagasaki University Hospital for oral rehabilitation. He had undergone interferon treatment for hepatitis C for 3 months before his first visit to our hospital. He did not have any hemostasis abnormalities, and there were no specific findings in his facial appearance. He exhibited severe periodontitis and had previously lost multiple teeth: Nos. 11, 12, 18, 21, 22, 25, 26, 28, 34, 37, 46, and 47. We concluded that the remaining teeth could not be preserved (Figure 1).

Bimaxillary implant-supported full arch rehabilitation was planned after all teeth had been extracted. Augmentation of the alveolar bone and bilateral sinus floor was necessary because of severe alveolar bone atrophy at the anterior region and insufficiency of alveolar bone height in the posterior maxillary region (approximately 2–3 mm; Figures 2 and 3). We planned grafting with a mixture of APDDM and PCBM for bone augmentation. Dental implants were planned to be placed with a staged approach after bone augmentation was completed. During the healing period, oral rehabilitation was performed with temporary implants and a prosthesis. The clinical use of APDDM was approved by the Ethical Committee for Clinical Studies of Nagasaki University Hospital (approval No. 11052368).

Nine teeth that exhibited severe mobility (Nos. 13–17, 35, 36, 38, and 48) were extracted under local anesthesia and preserved at −20°C. The remaining 11 teeth were removed under general anesthesia during the bone augmentation procedure. APDDM was prepared from all extracted teeth except for No. 16, in accordance with the method used in previous reports.^12,13  Briefly, extracted teeth were denudated of soft tissue and any restoration materials; they were then crushed with ice cubes by milling (Takigen, Tokyo, Japan), resulting in refined dentin particles with a diameter of approximately 1 mm. The dentin particles were partially demineralized in 2% HNO₃ and rinsed in 0.1 M Tris-HCl (pH 7.4). APDDM was prepared during the operation for bone augmentation.

A bone-supported surgical guide (Bionic Bone Navi System, BioNIC, Wada Precision Dental Laboratories, Osaka, Japan) was placed on the severe atrophied alveolar bone after mucoperiosteum flap elevation (Figure 4a and b). Guide pins (Nobel Biocare, Zürich-Flughafen, Switzerland) were temporarily inserted at the correct position as landmarks for temporary implants (Figure 4c). A bone window was created at the anterior wall of the maxillary sinus, and the sinus membrane was gently elevated to separate the sinus membrane from the bottom of the sinus floor (Figure 4d). Simultaneously, PCBM was harvested from the iliac bone, and APDDM was prepared in the laboratory. PCBM and APDDM were mixed at equal volume; for ease of handling, the mixture was gelatinized with autologous fibrinogen glue purified from peripheral blood. It was then used to fill the space between the bottom of the sinus floor and the sinus membrane (Figure 4e, h, and i).

Following the perforation of cortical bone in the anterior maxillary alveolar bone, the APDDM and PCBM mixture was grafted onto the atrophied alveolar bone to enhance the bone width and height. The mixture was covered by absorbable guided bone regeneration membrane (BIOMEND, Zimmer Biomet Dental, Palm Beach Gardens, Fla), and 0.1-mm-thick titanium mesh (Le Forte System, Jeil Medical, Seoul, Korea) was placed on the membrane to mold the shape of the alveolar bone (Figure 4f). Finally, 5 temporary implants (IP Implant, Nobel Biocare) were placed for temporary oral rehabilitation after surgery (Figure 4g). The acrylic resin provisional restoration was immediately loaded with temporary implants.

Bimaxillary provisional restorations were placed on the day after surgery. Cone-beam computerized tomography images were taken 3 months after bone augmentation; these confirmed that sufficient bone volume for dental implant placement was acquired in both the anterior and posterior regions of the maxilla (Figure 5). Following removal of the maxillary IP implants, 7 dental implants (Speedy Groovy, Nobel Biocare) were inserted with surgical guide navigation (Nobel Guide, Nobel Biocare) at 3.5 months after bone augmentation. All inserted implants had a diameter of 4.0 mm, while the lengths of the inserted implants were 10 mm at No. 12; 11.5 mm at Nos. 14, 17, 22, and 24; and 13 mm at Nos. 16 and 26. The provisional maxillary restoration was performed concurrently with dental implant placement in retaining by screws (Figure 6). Final restorations were placed in the mandible and maxilla at 13 and 21 months after bone augmentation, respectively. The final prosthesis was constructed by the titanium flame and hybrid resin with screw retaining. The occlusal contacts scheme was capsid-guided occlusion. There have been no major complications, including implantitis, for nearly 4 years since the placement of the final restorations. The bone level surrounding the dental implants had no remarkable bone absorption (Figures 7 and 8). Bone volume has been stable for 58 months after bone augmentation, as demonstrated by computerized tomography examination; computerized tomography images revealed that augmented bone appeared to be similar to natural bone with cortical bone and marrow (Figure 9).

Based on the outcome of the present case, grafting with the mixture of APDDM and PCBM could be an effective method of treatment for alveolar bone augmentation that requires a relatively large volume of bone regeneration; it could thus provide an excellent long-term prognosis. APDDM and PCBM may play synergistic roles in the induction and maturation of bone, and the 2 graft materials may compensate for each other's mutual disadvantages. PCBM has superior osteogenic potential because it contains both osteoblasts and osteoprogenitor cells but easily undergoes resorption. In contrast, APDDM has limited osteogenic potential but could be a suitable scaffold for osteoblastic cells. Furthermore, APDDM resists the rapid resorption of graft material. Complete resorption of DDM and remodeling into host bone has been reported to require >6 months.¹⁴  APDDM appears to resorb more slowly because it contains approximately 70% of original dentin matrix mineral. This partial demineralization of dentin matrix may affect the long-term stability of regenerated bone. Indeed, the augmented bone volume has been stable for nearly 58 months since bone augmentation using the mixture of APDDM and PCBM (Figures. 8 and 9).

Several clinical studies have demonstrated the effectiveness of DDM for bone augmentation and alveolar bone preservation after tooth extraction.^11,13–15  However, the bone defects were relatively small in those cases, because of the limited availability and insufficient osteoinductivity of DDM. To enhance the osteogenic activity of DDM, Um et al¹⁵  added recombinant bone morphogenetic protein (BMP)–2 to DDM and used this preparation for socket preservation; they presumed that the synergistic effect of exogenous BMP-2 and the growth factors released from DDM would enhance new bone formation. While DDM may constitute an excellent BMP-2 carrier, APDDM could be a suitable substrate for cell attachment and differentiation. Notably, partial demineralization of dentin exposes collagen fiber, which enables cells to easily attach to substrate; the growth factors released from APDDM might concurrently stimulate osteoblastic differentiation. Furthermore, residual mineral in APDDM could enhance osteoclastic activity, thereby promoting bone remodeling. These factors may have contributed to the rapid and sufficient bone formation for dental implant placement with primary fixation (within 3.5 months after bone augmentation), which enabled immediate temporary restoration in the present case.

Although APDDM may constitute an excellent bone graft, its most critical limitation is its availability. Few patients undergo extraction of a large number of teeth similar to the treatment plan in the present case. A solution for this problem may be the use of allogeneic dentin, as allogeneic bone matrix is widely applied clinically as freeze-dried bone allograft (FDBA) and demineralized freeze-dried bone allograft (DFDBA). Allogeneic dentin has some advantages relative to allogeneic bone. First, a specific amount of allogeneic partial DDM could be provided, because it could be prepared from discarded teeth (eg, wisdom teeth) that are extracted in dental offices. In contrast, FDBA and DFDBA are prepared from cadaver bones. Second, allogeneic dentin may be less likely to transmit unknown diseases, because the dentin matrix does not remodel after the completion of organization and does not have any blood vessels. In contrast, bone matrix exhibits continuous remodeling and has abundant blood vessels that may enable pathogen invasion. Further studies of the safety and efficacy of allogeneic partial DDM are needed, as are investigations of methods to establish a reliable source of allogeneic dentin.

In conclusion, grafting with the mixture of APDDM and PCBM was a reliable method for wide-range alveolar bone augmentation. The volume of bone augmented by the graft was maintained for an extended period, which might be an important consideration in the application of the APDDM and PCBM grafting mixture for extended regeneration of alveolar bone when a substantial number of teeth will be extracted.

Abbreviations

APDDM:

autogenous partially demineralized dentin matrix

DDM:

demineralized dentin matrix

DFDBA:

demineralized freeze-dried bone allograft

FDBA:

freeze-dried bone allograft

PCBM:

particulate cancellous bone and marrow

We thank Ryan Chastain-Gross, PhD, from the Edanz Group (https://www.edanzediting.com/ac) for editing a draft of this article.

The authors have no conflicts of interest to declare.