Journal of Dental Implant Research 2023; 42(2): 24-29  https://doi.org/10.54527/jdir.2023.42.2.24
Clinical outcomes of micro-sized autogenous demineralized dentin matrix for periodontal bone defects: A case report
Tae Hyeong 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, https://orcid.org/0000-0003-1192-7066
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, Deokjin-gu, Jeonju 54907, Korea. Tel: +82-63-250-2113, Fax: +82-63-250-2089, E-mail: kujk@jbnu.ac.kr
Received: May 31, 2023; Revised: June 16, 2023; Accepted: June 16, 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 (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Periodontal disease is a common oral health problem that can lead to tooth loss. The treatment of periodontal defects involves a resection and regenerative surgery. Autogenous demineralized dentin matrix (auto-DDM), a bone substitute derived from extracted teeth, has shown promise in regenerative periodontal surgery. This case report introduces the clinical outcomes of micro-sized DDM for periodontal bone defects. This case report presents the clinical outcomes of microparticle-sized auto-DDM (<200 μm) for treating periodontal bone defects. A 44-year-old woman with premolar mobility underwent a bone graft for an auto-DDM. The results revealed improved alveolar bone stability and reduced periodontitis symptoms. A radiographic examination revealed increased radio-opacity in the defective area, indicating bone regeneration. Fine-sized auto-DDM particles facilitated the release of growth factors and promoted osteoinductivity. The absence of a barrier membrane did not impede the successful outcomes. Auto-DDM can be used as a biomaterial for periodontal regeneration by delivering endogenous growth factors. Further prospective studies and histological analyses will be needed to validate its effectiveness in regenerating the periodontal ligament and alveolar bone.
Keywords: Periodontitis, Demineralized dentin matrix, Bone regeneration, Dentistry
INTRODUCTION

Periodontal disease is a common oral health problem that can result in the loss of support for the gingiva, eventually leading to tooth loss. The treatment of periodontal defects is divided into two approaches: resective surgery and regenerative surgery1). Resective surgery involves the removal of diseased tissue, such as infected periodontal tissue, to reduce inflammation and improve oral health. In contrast, regenerative periodontal surgery aims to restore damaged or lost tissues, including alveolar bone and periodontal tissue. Regenerative periodontal surgery involves the use of regenerative materials, such as bone substitutes and growth factors, to stimulate the growth of new tissue. Autogenous bone is currently regarded as the optimal option because of its osteoconductivity, osteoinductivity, and osteogenic capacity, along with numerous growth factors2). However, because of the limited availability of autogenous bone, various bone substitutes have been developed for tissue engineering. One such substitute is the autogenous demineralized dentin matrix (auto-DDM), which is derived from a patient's extracted tooth and contains hydroxyapatite, type I collagen, and matrix proteins3). Additionally, regenerative materials, such as bone morphogenetic protein (BMP) and enamel matrix derivatives, have been used.

The chemical composition of dentin is similar to that of bones. Auto-DDM is used in dental implant treatment because it contains endogenous growth factors, or non-collagenous proteins (NCPs), including BMP-2, transforming growth factor-beta, platelet-derived growth factor, fibroblast growth factor, and insulin-like growth factor. In 2022, Kim et al.4) reported the significant impact of Auto-DDM on regeneration of a periodontal bony defect and soft tissue healing at the distal aspect of the mandibular second molar after third molar extraction. Bone substitutes ranging from 300 to 800 µm in size are commonly used for dental implants in jaw defects. As the size of the DDM particles decreases, the surface area increases, allowing for better release of NCPs and promoting osteoinductivity. However, if DDM particles are too small to exhibit osteoclastic activity, their minimum osteoconductivity may be lost, and graft effectiveness may diminish.

Contemporary dentistry places greater emphasis on meeting patient expectations. While dental implant treatment has become the preferred approach for restoring teeth and periodontal components, both patients and clinicians often opt for tooth extraction in cases of damage to the alveolar bone and gingiva1). Nevertheless, periodontal regeneration is an alternative for preserving a patient’s natural teeth. Consequently, the aim of this case report was to present the clinical results achieved through the utilization of microparticle-sized Auto-DDM (<200 µm) for the treatment of periodontal bone defects.

CASE REPPORT

A 44-year-old woman with premolar mobility in the left mandible presented to our hospital. Radiographic examinations and clinical tests were performed (Fig. 1). The results indicated that she had grade 2 mobility in tooth #34 along with periodontal defects, such as marginal bone loss and gingival redness (Fig. 1B).

Figure 1. Preoperative clinical and radiographic images. (A) Periodontal defect on the left mandibular first premolar. (B) Localized swelling and redness of gingiva at the left mandibular first premolar.

Bone grafting was planned to enhance alveolar bone stability. The right maxillary molar (#17) was chosen for extraction because of a root fracture. It was then sent to a manufacturer (Korea Tooth Bank, Seoul, Republic of Korea) for processing into Auto-DDMs (AutoBT®). The remaining periodontal and soft tissues were then excised. Cementum and enamel were ground using a rotating instrument (Diamond Bur; Rodent AG, Seoul, Korea). The root canal filling was removed. Subsequently, the tooth was processed for ABTB fabrication (European Patent No. 2462899), as described in previous reports5,6). In brief, auto-DDM underwent demineralization, defatting, dehydration, and freeze-drying. The Auto-DDM particles were prepared to a size <200 µm (Fig. 2C). Since the degree of mobility was grade III, resin splint was applied. Following an envelope incision and elevation of the mucoperiosteal flap (Fig. 2A), the periodontal defect was exposed. Curettage and root planing were performed to remove the inflammatory granulation tissues (Fig. 2B). The hydrated auto-DDM was then grafted onto the defect area (Fig. 2D, E). Suturing was performed using 5-0 nylon without a membrane (Fig. 2F).

Figure 2. Clinical images of the surgical procedure. (A) After envelope incision and mucoperiosteal flap elevation. (B) After elimination of inflammatory granulation tissue by curettage and root planing. (C) Fine-size particle of autogenous demineralized dentin matrix. (D) Hydrated autogenous demineralized dentin matrix. (E) Auto-DDM was packed into the periodontal defect area. (F) Suturing carried out using 5-0 nylon without a membrane.

On postoperative day 17, the stitches were removed without complications (Fig. 3A). The resin splint was removed five months postoperatively. Radiographic examinations were performed immediately and 5 and 12 months postoperatively. Periapical standard views revealed increased radiopacity in the defect area (Fig. 3D∼F). Postoperative clinical images demonstrated reduction in periodontitis symptoms, such as swelling and redness (Fig. 3B, C). Beyond improvement in the radiographic results, clinical mobility of the teeth was significantly reduced, going from grade 2 to grade 0.

Figure 3. Postoperative images. (A) Clinical image 2 weeks postoperatively. (B) Clinical image 5 months postoperatively. (C) Clinical image 12 months postoperatively. (D) Periapical standard view immediately postoperatively. (E) Periapical standard view 5 months post-operatively. (F) Periapical standard view 12 months postoperatively.
DISCUSSION

Typically, a range of 300∼800 µm is considered ideal for DDM (Auto-BT) regarding bioactive scaffolds for osteoclastic activity and coupling with osteoblasts. Nam et al.7) found that DDM ranging from 250 to 1,000 µm were more effective in promoting bone formation compared to particles larger than 1,000 µm. However, there were limited studies evaluating the effect of micro-size range of DDM. Because a particle size of over 300 µm is too large to fit into a periodontal pocket, a fine powder measuring ≤200 µm should be present to enter the pocket. Upon examination of the patient’s results, bony regeneration was evident using the fine-sized DDM, although the HA content was so small that the transplanted bone was not visible on the radiograph immediately postoperatively. While smaller sizes may pose challenges for stable bone healing, rapid absorption of fine-sized DDM particles could release various growth factors bound to the HA-collagen matrix, potentially offering more advantages than larger particles.

Although numerous membranes for periodontal regeneration have been developed in recent years, these barrier membranes prevent the ingrowth of epithelial cells and provide space to regenerate periodontal ligament and alveolar bone8). Guided tissue regeneration (GTR) employs a barrier membrane around the periodontal defect to prevent epithelial downgrowth and fibroblast transgrowth into the wound space, thereby maintaining a space for true periodontal tissue regeneration8). As the concept of tissue engineering has developed, third-generation membranes have evolved, which act as barriers and delivery devices to release specific agents, such as antibiotics, growth factors, adhesion factors, etc9). However, most of them are still in the laboratory stages. The current lack of membranes with improved properties hampers the attainment of successful treatment outcomes10). In this study, DDM showed acceptable results without using a membrane. DDM mainly consists of type I collagen, which is the major protein of intertubular dentin and packed collagen fibers of 20∼50 nm11,12), which can act as osteoinductive collagen membranes with mechanical and clot stability, thereby replacing the osteogenic function of the periosteum13). Hence, the application of a barrier membrane was deemed unnecessary.

Depending on whether or not biomaterials are used, tissue engineering strategies for periodontal regeneration can be categorized into scaffold-free and scaffold-based approaches10). In the scaffold-free approach, cells or cell aggregates are transplanted into a defect area without a cell carrier. Several cell types, including bone marrow-derived mesenchymal, periodontal ligament, adipose-derived, and dental pulp stem cells, have been tested for their potential to form periodontal tissues14-16). Direct cell implantation faces the problem of cell diffusion from the defect area. The cell sheet technique, which entraps cells in an extracellular matrix (ECM) secreted by the cells, can prevent cell migration. Cell sheet therapy induces more bone formation than cell suspensions in swine periodontal defects17). However, cell sheet technology can regenerate only a layer of tissue with a simple structure. Considering the complicated architecture of the periodontium, which includes two hard tissues (alveolar bone and cementum) and a soft tissue (periodontal ligament), the use of a scaffold-based approach is the only choice for regeneration of the periodontal ligament–cementum–alveolar bone complex18). However, an ideal strategy has not been suggested, and efforts are still required to improve regenerative outcomes for damaged periodontal components, such as the alveolar bone, gingiva, and periodontal ligament. In this case, the author used DDM as a scaffold-free approach. Considering that DDM has been proposed as a potential carrier of growth factors such as rhBMP-218), further research would be required to utilize DDM as carrier for cells.

DDM contains various endogenous growth factors, with TGF-β1 being the most abundant; FGF2, BMP-2, IGF-1, and vascular endothelial growth factor (VEGF) present in intermediate amounts; and BMP-4 and BMP-7 being the least abundant3). Among these, FGFs, PDGF, and VEGF promote the differentiation and growth of different cells involved in soft tissue healing, such as fibroblasts and osteoblasts19). TGF-β1 has a wide range of actions in various wound healing processes, including angiogenesis, inflammation, fibroblast proliferation, and collagen synthesis. It affects all cell types and plays a role in all stages of soft tissue healing. Therefore, the release of NCPs in DDM could initiate the healing process for alveolar bone remodeling and soft tissue regeneration related to the periodontium20). Two recent clinical split-mouth trials conducted in 2020 and 2022 demonstrated a reduction in the probing depth when using tooth bone21,22). Another clinical study also showed that DDM could improve alveolar bone healing in cases of exposed tooth roots4). Based on these results, DDM has high potential as a biomaterial for periodontal regeneration with various growth factors as a bioactive scaffold. However, owing to the limitations of retrospective case reports, we could not perform a histological analysis to confirm the regeneration of the periodontal ligament or alveolar bone. Nevertheless, evidence of bone healing was observed on the radiographs. Further prospective studies on alveolar bone regeneration in periodontal defects, including histological analyses, should be conducted based on the findings of the present study.

CONCLUSION

In this case report, the use of a microparticle-sized autogenous demineralized dentin matrix (auto-DDM) for the treatment of periodontal bone defects showed promising clinical results, even without any barrier membrane. Although scaffold-based approaches are necessary to regenerate complex periodontal components, auto-DDM shows potential as a biomaterial for periodontal regeneration, delivering endogenous growth factors, and promoting healing. Further prospective studies and histological analyses are required to validate the effectiveness of auto-DDM in regenerating the periodontal ligament and alveolar bone.

References
  1. Kwon T, Lamster IB, Levin LJIdj. Current concepts in the management of periodontitis 2021;71:462-76.
    Pubmed KoreaMed CrossRef
  2. Jang KY, Lee JH, Oh SH, Ham BD, Chung SM, Lee JK, et al. Bone graft materials for current implant dentistry. Journal of Dental Implant Research 2020;39:1-10.
    CrossRef
  3. Avery SJ, Sadaghiani L, Sloan AJ, Waddington RJ. Analysing the bioactive makeup of demineralised dentine matrix on bone marrow mesenchymal stem cells for enhanced bone repair. Eur Cell Mater 2017;34:1-14.
    Pubmed CrossRef
  4. Kim Y, Ku JK, Um IW, Seok H, Leem DH. Impact of autogenous demineralized dentin matrix on mandibular second molar after third molar extraction: retrospective study. J Funct Biomater 2022;14.
    Pubmed KoreaMed CrossRef
  5. Um IW, Ku JK, Lee BK, Yun PY, Lee JK, Nam JH. Postulated release profile of recombinant human bone morphogenetic protein-2 (rhBMP-2) from demineralized dentin matrix. Journal of the Korean Association of Oral and Maxillofacial Surgeons 2019;45:123-8.
    KoreaMed CrossRef
  6. Um IW, Ku JK, Kim YM, Yun PY, Chang NH, Kim YK, et al. Allogeneic demineralized dentin matrix graft for guided bone regeneration in dental implants. Applied Sciences 2020;10:4661.
    CrossRef
  7. Nam JW, Kim MY, Han SJ. Cranial bone regeneration according to different particle sizes and densities of demineralized dentin matrix in the rabbit model. Maxillofac Plast Reconstr Surg 2016;38:27.
    KoreaMed CrossRef
  8. Sam G, Pillai BR. Evolution of barrier membranes in periodontal regeneration-"are the third generation membranes really here?". J Clin Diagn Res 2014;8:Ze14-7.
    Pubmed KoreaMed CrossRef
  9. Wang HL, MacNeil RL. Guided tissue regeneration. Absorbable barriers. Dent Clin North Am 1998;42:505-22.
    Pubmed CrossRef
  10. Liang Y, Luan X, Liu X. Recent advances in periodontal regeneration: a biomaterial perspective. Bioact Mater 2020;5:297-308.
    Pubmed KoreaMed CrossRef
  11. Goldberg M, Kulkarni AB, Young M, Boskey A. Dentin: structure, composition and mineralization. Frontiers in bioscience (Elite edition) 2011;3:711-35.
    Pubmed KoreaMed CrossRef
  12. Murata M. Collagen biology for bone regenerative surgery. J Korean Assoc Oral Maxillofac Surg 2012;38:321-5.
    CrossRef
  13. Ku JK, Um IW, Jun MK, Kim IH. Dentin-derived-barrier membrane in guided bone regeneration: a case report. Materials (Basel) 2021;14.
    Pubmed KoreaMed CrossRef
  14. Yu BH, Zhou Q, Wang ZL. Periodontal ligament versus bone marrow mesenchymal stem cells in combination with Bio-Oss scaffolds for ectopic and in situ bone formation: a comparative study in the rat. J Biomater Appl 2014;29:243-53.
    Pubmed CrossRef
  15. Seo BM, Miura M, Gronthos S, Bartold PM, Batouli S, Brahim J, et al. Investigation of multipotent postnatal stem cells from human periodontal ligament. Lancet 2004;364:149-55.
    Pubmed CrossRef
  16. Liu Y, Zheng Y, Ding G, Fang D, Zhang C, Bartold PM, et al. Periodontal ligament stem cell-mediated treatment for periodontitis in miniature swine. Stem Cells 2008;26:1065-73.
    Pubmed KoreaMed CrossRef
  17. Hu J, Cao Y, Xie Y, Wang H, Fan Z, Wang J, et al. Periodontal regeneration in swine after cell injection and cell sheet transplantation of human dental pulp stem cells following good manufacturing practice. Stem Cell Res Ther 2016;7:130.
    Pubmed KoreaMed CrossRef
  18. Bousnaki M, Beketova A, Kontonasaki E. A review of in vivo and clinical studies applying scaffolds and cell sheet technology for periodontal ligament regeneration. Biomolecules 2022;12.
    Pubmed KoreaMed CrossRef
  19. Dimitriou R, Tsiridis E, Giannoudis PV. Current concepts of molecular aspects of bone healing. Injury 2005;36:1392-404.
    Pubmed CrossRef
  20. Um IW, Ku JK, Kim YK, Lee BK, Leem DH. Histological review of demineralized dentin matrix as a carrier of rhBMP-2. Tissue Eng Part B Rev 2020;26:284-93.
    Pubmed KoreaMed CrossRef
  21. Sánchez-Labrador L, Martín-Ares M, Ortega-Aranegui R, López-Quiles J, Martínez-González JM. Autogenous dentin graft in bone defects after lower third molar extraction: a split-mouth clinical trial. Materials (Basel) 2020;13.
    Pubmed KoreaMed CrossRef
  22. Wushou A, Zheng Y, Han Y, Yang Zc, Han Fk. The use of autogenous tooth bone graft powder in the treatment of osseous defects after impacted mandibular third molar extraction: a prospective split-mouth clinical pilot study. BMC Oral Health 2022;22:433.
    Pubmed KoreaMed CrossRef


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