Journal of Dental Implant Research 2023; 42(2): 19-23
Long-term effects of demineralized bone matrix incorporated with recombinant bone morphogenetic protein (rhBMP)-2 on large maxillary cystic defects
Sang-Hee Park , Jeong-Kui Ku
Department of Oral and Maxillofacial Surgery, School of Dentistry and Institute of Oral Bioscience, Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonbuk National University, Jeonju, Korea
Correspondence to: Jeong-Kui Ku,
Department of Oral and Maxillofacial Surgery, School of Dentistry and Institute of Oral Bioscience, Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonbuk National University, 567 Baekje-daero, Deokin-gu, Jeonju 54907, Korea. Tel: +82-63-250-2113, Fax: +82-63-250-2089, E-mail:
Received: May 8, 2023; Revised: May 26, 2023; Accepted: May 30, 2023; Published online: June 30, 2023.
© The Korean Academy of Implant Dentistry. All rights reserved.

This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Bone grafts are regularly performed in implant dentistry and several bone substitutes with enhanced safety and efficacy have been developed and introduced. Surgery is one of the common treatments for jaw cysts which may result in postoperative defects or alter the facial contours. Although a large cyst can be reduced in size with decompression over a few months, some of them still leave a large cystic lesion, which may require a bone graft. However, the benefits of using bone substitutes in cystic defects for better post-operative healing and bone regeneration are still quite controversial. This case report aims to demonstrate the long-term outcome of a demineralized bone matrix incorporated with recombinant human bone morphogenic protein-2 on a large maxillary cyst.
Keywords: Bone graft, Cyst, Demineralized bone matrix, rhBMP-2, Maxilla

A cyst is a pathologic cavity that may contain fluid and is lined with epithelial cells. Jaw cysts vary in their etiology, incidence, location, clinical characteristics, and treatments. Jaw cysts can be treated by enucleation, marsupialization, enucleation after marsupialization, and surgical removal. After enucleation treatment, the cavity may heal spontaneously due to bone remodeling1). The blood clot formed after enucleation serves as a biological scaffold for inflammatory cell migration, proliferation, and growth factor production2). In 2022, Ku et al.3) reported that intra-osseous bone healing was approximately 75% in three dimensions. Therefore, in larger cysts, additional bone grafts can be used to fill the cavity to prevent pathological fractures and encourage rapid bone healing4).

Autogenous bone grafts have long been considered the “gold standard”5), but due to the complications of additional surgery, tissue damage, bone resorption, and donor site limitations, alternatives have been developed. Tissue engineering studies have developed xenograft/synthetic bones with excellent osteoconductivity but are difficult to remodel into functional bone. Allografts have potential for bone remodeling into functional bone, but they can develop necrosis/infection in defective areas with poor blood supply. Therefore, recombinant human bone morphogenetic proteins (rhBMP-2 were developed to improve bone regeneration and are known to induce bone and cartilage formation. Among them, rh-BMP-2 and 7 have been reported to have superior bone-inducing abilities6). However, there are problems with their scaffolds. Rapid release in vivo can cause side effects such as ectopic bone formation, erythema, and swelling. In 2020, Hwang and Ku4) reported initial results of DBM/ rhBMP-2, which include gingival swelling and erythema, possibly due to the initial burst release of rhBMP-2. Therefore, it is important to choose an efficient carrier of BMPs that is not harmful to surrounding tissue and can effectively accommodate and deliver BMPs.

Demineralized bone matrix (DBM) is allogenic bone that has both osteoconductive and osteoinductive abilities. It serves as a scaffold for bone healing and a carrier for various growth cells. By applying rhBMP-2, which has angiogenesis and osteoinductivity, to DBM with the ability of bone induction and bone conductivity, effective bone regeneration can occur in large cystic defects. In this case report, a large maxillary cystic lesion was filled with DBM incorporated with rhBMP-2 (DBM/rhBMP-2). This is long-term follow up of previous case report4), and aims to evaluate the long-term results of DBM/rhBMP-2 on large cystic defects by showing biopsy results eight months after the operation and radiographs three years after the operation.


A 22-year-old male presented with swelling on his left cheek and restricted mouth opening. Radiographic examination revealed a large cystic lesion with a diameter of approximately 10 cm on the right anterior to the left maxilla (Fig. 1).

Figure 1. Panoramic radiograph showing radiolucency on the maxillary right anterior to the left.

The patient underwent decompression and incisional biopsy was performed. Histologic results indicated dentigerous cyst. 14 weeks of marsupialization, however, there was no change in the cystic size. The patient underwent decompression for 14 weeks, however, there was no change in the cystic size (Fig. 2A). Therefore, surgery to enucleate the cyst under general anesthesia was planned. Cyst was carefully enucleated. There was partial missing of posterior wall of cystic cavity with perforation of sinus schneiderian membrane. Perforation of maxillary sinus schneiderian membrane was repaired with suture, fibrin glue (Greenplast Q, GC pharma., Kyonggi-Do, Korea) and oxygenized regenerated cellulose (Surgicel, Ethicon from Johnson & Johnson, New Jersey, USA). Due to the anticipated significant defects, a bone graft was performed using DBM/rhBMP-2 (Bio-BMP 2, celled, Seoul, Republic of Korea) and a titanium mesh to contour the bone. Although gingival swelling and erythema were observed early on after the surgery, the patient recovered without infection or wound rupture4). At 6 months after operation, CT showed increased radiopacity indicating remodeling without central necrosis even though a large defect (Fig. 2B).

Figure 2. Pre- and post-operative CT images. (A) Pre-operative. (B) Post-operative six months with bone graft of DBM/rhBMP-2 fixed with titanium mesh.

At eight months after the operation, the titanium mesh was removed (Fig. 3A). A softened area was identified, indicating the central area where the radiopacity did not increase on the CT scan. This area was removed (Fig. 3B, C) and the defect was once again packed with DBM/rhBMP-2 (Fig. 3D). The grafts were covered with ossgide (SK Bioland, Cheonan, Korea) and sutured. A biopsy was performed on the softened area. The biopsy of the softened area showed DBM particles that remained as dead bone fragments covered with a fibrous capsule (Fig. 4).

Figure 3. 8 Months after cyst enucleation. (A, B) Mesh was removed and softened part was detected. (C) Softened part has removed and biopsy was performed. (D) Defect was refilled with DBM/rhBMP-2.
Figure 4. Biopsy specimen and its histologic aspect. (A) Softened bone fragments. (B, C) Hematoxylin and eosin staining. There were non-vital bone particles (*) were mainly observed with fibrous capsule and osteoclast (arrows).

After three years of repacking with DBM/rhBMP-2, there was no sign of recurrence, and a CT scan showed bone remodeling, indicating that the cystic defect had regenerated into cortico-cancellous bone (Fig. 5).

Figure 5. Images at 3-year after operation. (A) Intraoral image. None of gingival swelling or erythema were found. (B) Computer tomography at 3 years after operation. Overall radiopacity on cystic defect which implies cortico-cancellous bone remodeling.

This case report is a long-term follow up of previous report4). In this case, a large cystic lesion in the maxillary area was treated with decompression to reduce the cystic volume, but a significant cystic defect was expected. The authors decided to use DBM/rhBMP-2 with a titanium mesh. After eight months, the mesh was removed. There was softened bone inside the mesh, and removed it to histologic analysis and simultaneously re-grafted with DBM/rhBMP-2. The histology showed were non-vital bone particles with fibrous capsule and osteoclast, which indicating incomplete remodeling process. Three years after the operation, a CT scan showed bone remodeling into functional cortico-cancellous bone.

The use of bone graft materials in cystic defects is controversial. Some researchers have shown that spontaneous bone regeneration can be achieved by cyst enucleation without bone grafting materials2,7). On the other hands, other studies have demonstrated spontaneous bone regeneration even after enucleation of large cysts without any bone graft materials8). However, in cases of damaged periosteum or bone walls, bone grafts may be required, and there are also studies that show the advantages of bone grafts on bone regeneration after the cyst enuclation7,9). In this case report, a large defect in the maxilla into the maxillary sinus was identified. In addition, delayed angiogenesis of bone graft materials in large defects can increase the risk of central necrosis due to the lack of neovascularization into the center4). Therefore, DBM/rhBMP-2, known for its superior osteoinductivity, was used in this case.

While rhBMP-2 has been approved by the FDA for use in human surgery, its use has been associated with soft tissue inflammation and swelling in some cases10). Studies about BMP induced inflammation, Lee et al.10) showed both rhBMP-2 and rhBMP-7 induced high level of IL-6 which is inflammatory mediator and concluded both rhBMP-2 and rhBMP-7 triggers dose-dependent inflammatory reactions. In previous report, gingival swelling and erythematous occurred at 7 days after first operation in this case, which seems to be due to initial burst releasing of rhBMP-2 or inflammatory reaction of rhBMP-24). Regarding the initial result of filling the defect with a bone graft material obtained by soaking rhBMP-2 in DBM, it appears that DBM is not a good carrier of rhBMP-2. However, after eight months of bone grafting, the remaining DBM particles were found to be a dead bone matrix histopathologically, but in terms of the possibility of bone remodeling, the particles are non-vital cortical bone that can be absorbed by osteoclasts and become osteoblast coupling11). Therefore, rhBMP-2 was applied again eight months after the first surgery so that remaining DBM particles that were not used during bone remodeling after the first surgery could be remodeled to cortico-cancellous bone. Even if the titanium mesh had not been removed at eight months after the first operation in this case, there is a possibility that bone healing might have occurred as remaining DBM particles were absorbed.


In conclusion, this case report highlights the use of DBM/rhBMP-2 in the treatment of a large cystic lesion in the maxillary area. Histopathological analysis showed that remaining DBM particles after bone remodeling were non-vital cortical bone that could be absorbed by osteoclasts and become osteoblast coupling, indicating the potential for bone remodeling. Overall, this case demonstrated the potential benefits and challenges of using bone graft materials in the treatment of cystic lesions in the maxillary area.




Due to the retrospective nature of this case report, it was granted a written exemption by the was approved by the Armed Forces Capital Hospital Institutional Review Board (AFCH-21-IRB-001). The authors report no conflicts of interest related to this study.

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