Fundamentals and Translational Applications of Stem Cells and Biomaterials in Dental, Oral and Craniofacial Regenerative Medicine.

Regenerative dental medicine continuously expands to improve treatments for prevalent clinical problems in dental and oral medicine. Stem cell based translational opportunities include regenerative therapies for tooth restoration, root canal therapy, and inflammatory processes (e.g., periodontitis). The potential of regenerative approaches relies on the biological properties of dental stem cells. These and other multipotent somatic mesenchymal stem cell (MSC) types can in principle be applied as either autologous or allogeneic sources in dental procedures. Dental stem cells have distinct developmental origins and biological markers that determine their translational utility. Dental regenerative medicine is supported by mechanistic knowledge of the molecular pathways that regulate dental stem cell growth and differentiation. Cell fate determination and lineage progression of dental stem cells is regulated by multiple cell signaling pathways (e.g., WNTs, BMPs) and epigenetic mechanisms, including DNA modifications, histone modifications, and non-coding RNAs (e.g., miRNAs and lncRNAs). This review also considers a broad range of novel approaches in which stem cells are applied in combination with biopolymers, ceramics, and composite materials, as well as small molecules (agonistic or anti-agonistic ligands) and natural compounds. Materials that mimic the microenvironment of the stem cell niche are also presented. Promising concepts in bone and dental tissue engineering continue to drive innovation in dental and non-dental restorative procedures.

Evaluation of alveolar ridge preservation in sockets with buccal dehiscence defects using two types of xenogeneic biomaterials: An in vivo experimental study.

OBJECTIVES: Alveolar ridge preservation (ARP) has been extensively investigated in various preclinical and clinical studies, yielding favorable results. We aim to evaluate the effects of ARP using collagenated bovine bone mineral (CBBM) alone or particulated bovine bone mineral with a non-cross-linked collagen membrane (PBBM/NCLM) in tooth extraction sockets with buccal dehiscence in an experimental dog model. MATERIALS AND METHODS: The mesial roots of three mandibular premolars (P2, P3, and P4) were extracted from six mongrel dogs 4 weeks after inducing dehiscence defects. ARP was randomly performed using two different protocols: 1) CBBM alone and 2) PBBM/NCLM. Three-dimensional (3D) volumetric, micro-computed tomography, and histological analyses were employed to determine changes over a span of 20 weeks. RESULTS: In 3D volumetric and radiographic analyses, CBBM alone demonstrated similar effectiveness to PBBM/NCLM in ARP (p > .05). However, in the PBBM/NCLM group (3.05 ± 0.60 mm), the horizontal ridge width was well maintained 3 mm below the alveolar crest compared with the CBBM group (2.11 ± 1.01 mm, p = .002). CONCLUSION: Although the radiographic changes in the quality and quantity of bone were not significant between the two groups, the use of PBBM/NCLM resulted in greater horizontal dimensions and more favorable maintenance of the ridge profile.

Surface Topography of Titanium Affects Their Osteogenic Potential through DNA Methylation.

It is widely accepted that sandblasted/large-grit/acid-etched (SLA) surfaces of titanium (Ti) have a higher osteogenic potential than machined ones. However, most studies focused on differential gene expression without elucidating the underlying mechanism for this difference. The aim of this study was to evaluate how the surface roughness of dental Ti implants affects their osteogenic potential. Mouse preosteoblast MC3T3-E1 cells were seeded on machined and SLA Ti discs. The cellular activities of the discs were analyzed using confocal laser scanning microscopy, proliferation assays, and real-time polymerase chain reaction (PCR). DNA methylation was evaluated using a methylation-specific PCR. The cell morphology was slightly different between the two types of surfaces. While cellular proliferation was slightly greater on the machined surfaces, the osteogenic response of the SLA surfaces was superior, and they showed increased alkaline phosphatase (Alp) activity and higher bone marker gene expression levels (Type I collagen, Alp, and osteocalcin). The degree of DNA methylation on the Alp gene was lower on the SLA surfaces than on the machined surfaces. DNA methyltransferase inhibitor stimulated the Alp gene expression on the machined surfaces, similar to the SLA surfaces. The superior osteogenic potential of the SLA surfaces can be attributed to a different epigenetic landscape, specifically, the DNA methylation of Alp genes. This finding offers novel insights into epigenetics to supplement genetics and raises the possibility of using epidrugs as potential therapeutic targets to enhance osteogenesis on implant surfaces.

A randomized controlled clinical trial evaluating efficacy and adverse events of different types of recombinant human bone morphogenetic protein-2 delivery systems for alveolar ridge preservation.

OBJECTIVES: This 12-week clinical trial evaluated efficacy and adverse events for two recombinant human bone morphogenetic protein-2 (rhBMP-2) delivery systems in alveolar ridge preservation. MATERIALS AND METHODS: Sixty-four patients had a single tooth that required replacement with an implant, surrounded by > 50% alveolar bone height. Two cohorts (n = 32 patients each) were randomized to receive a rhBMP-2-soaked absorbable collagen sponge (test group), or ß-tricalcium phosphate and hydroxyapatite particles (control group) immersed in rhBMP-2, at the implant site. Bone height and width changes at 25%, 50%, and 75% of extraction socket level (ESL) were compared. Adverse events were assessed in the same period. In addition to the randomized controlled clinical trial, histological analysis of 21 patients (test group [n = 12], control group [n = 9]) was conducted, 4 months after alveolar ridge preservation. A non-inferiority test was used to analyze changes in alveolar bone height between groups (p = 0.05). A Wilcoxon rank-sum test was used to analyze changes in alveolar bone width and histomorphometric results between groups (p = 0.05). RESULTS: All patients showed good healing without severe adverse events. The lower limit of the one-sided 97.5% confidence interval in the difference between the two groups was 0.0033 (non-inferiority margin: -0.185); thus, the test group showed non-inferiority to the control group. Wilcoxon rank-sum test analysis did not show statistically significant differences between groups with regard to changes in alveolar bone width and histomorphometric analysis. CONCLUSIONS: The delivery systems showed similar efficacy for alveolar ridge preservation without severe adverse events.

Comparison of the osteogenic potential of titanium- and modified zirconia-based bioceramics.

Zirconia is now favored over titanium for use in dental implant materials because of its superior aesthetic qualities. However, zirconia is susceptible to degradation at lower temperatures. In order to address this issue, we have developed modified zirconia implants that contain tantalum oxide or niobium oxide. Cells attached as efficiently to the zirconia implants as to titanium-based materials, irrespective of surface roughness. Cell proliferation on the polished surface was higher than that on the rough surfaces, but the converse was true for the osteogenic response. Cells on yttrium (Y)/tantalum (Ta)- and yttrium (Y)/niobium (Nb)-stabilized tetragonal zirconia polycrystals (TZP) discs ((Y, Ta)-TZP and (Y, Nb)-TZP, respectively) had a similar proliferative potential as those grown on anodized titanium. The osteogenic potential of MC3T3-E1 pre-osteoblast cells on (Y, Ta)-TZP and (Y, Nb)-TZP was similar to that of cells grown on rough-surface titanium. These data demonstrate that improved zirconia implants, which are resistant to temperature-induced degradation, retain the desirable clinical properties of structural stability and support of an osteogenic response.

Clinical evaluation of 3.0-mm narrow-diameter implants: a retrospective study with up to 5 years of observation.

PURPOSE: This study aimed to evaluate the clinical outcomes of a single type of narrow-diameter implant (NDI) by investigating its survival rate and peri-implant marginal bone loss (MBL). In addition, variables possibly related to implant survival and MBL were investigated to identify potential risk factors. METHODS: The study was conducted as a retrospective study involving 49 patients who had received 3.0-mm diameter TSIII implants (Osstem Implant Co.) at Seoul National University Dental Hospital. In total, 64 implants were included, and dental records and radiographic data were collected from 2017 to 2022. Kaplan-Meier survival curves and a Cox proportional hazard model were used to estimate the implant survival rate and to investigate the effects of age, sex, jaw, implant location, implant length, the stage of surgery, guided bone regeneration, type of implant placement, and the surgeon's proficiency (resident or professor) on implant survival. The MBL of the NDIs was measured, and the factors influencing MBL were evaluated. RESULTS: The mean observation period was 30.5 months (interquartile range, 26.75-45 months), and 6 out of 64 implants failed. The survival rate of the NDIs was 90.6%, and the multivariate Cox regression analysis showed that age was associated with implant failure (hazard ratio, 1.17; 95% confidence interval, 1.04-1.31, P=0.01). The mean MBL was 0.44±0.75 mm, and no factors showed statistically significant associations with greater MBL. CONCLUSIONS: NDIs can be considered a primary alternative when standard-diameter implants are unsuitable. However, further studies are required to confirm their long-term stability.

The activin/BMP-2 chimera AB204 promotes periodontal tissue regeneration in a buccal dehiscence model: a pilot study.

PURPOSE: A combination of activin and bone morphogenetic protein-2 (BMP-2), termed AB204, has been shown to improve osteogenic potential with fewer side effects than BMP-2 alone. This study was performed to evaluate the effect of AB204 on periodontal tissue regeneration in a dog buccal dehiscence model. METHODS: Buccal dehiscence defects were created on the maxillary premolars (P1, P2, and P3) of 6 mongrel dogs. After 5 weeks, the dogs were randomly assigned to 1 of 3 groups: the control, collagen matrix (CM), and CM/AB204 groups. Grafting procedures were then performed. The dogs were sacrificed 8 weeks after the grafting procedure, and volumetric and histological analyses were conducted. RESULTS: The thickness of the buccal gingiva in the CM/AB204 group was greater than those in the other groups at 2 weeks (P<0.05). The ridge width in the AB204/CM group exceeded the width in the other groups at 4 and 8 weeks; however, the difference was not statistically significant. Histological analysis revealed that the CM/AB204 group demonstrated the formation of new bone surrounded by newly formed periodontal ligament and cementum (P=0.035). CONCLUSIONS: The combined application of CM and AB204 shows promise in facilitating the regeneration of periodontal attachment, including the formation of new bone, cementum, and periodontal ligament.

Bone regeneration using activin A/BMP2 chimera (AB204) with collagen membrane in rats with calvarial defects.

PURPOSE: Collagen has long been recognized as an excellent carrier for growth factors, and membrane-type collagen has been widely applied in dentistry for guided bone regeneration. This study was conducted to examine the effects of an activin A/BMP2 chimera (AB204) combined with a collagen membrane (CM) on bone repair in a rat calvarial defect model. METHODS: A unilateral calvarial defect measuring 5.0 mm was surgically created in 32 Sprague-Dawley rats. The rats were then randomly assigned to 1 of 4 groups, each consisting of 8 animals: control (untreated), CM (treated with a CM only), CM/bone morphogenetic protein 2 (BMP2) (treated with a CM and 1.0 µg of BMP2), and CM/AB204 (treated with a CM and 1.0 µg of AB204). Bone regeneration was evaluated using micro-computed tomography (CT) and histological analysis at 2 and 4 weeks following surgery. RESULTS: Micro-CT analysis revealed that bone formation in the CM/BMP2 and CM/AB204 groups was superior to that observed in the control and CM groups at both 2 and 4 weeks postoperatively. BMP2 induced greater bone regeneration than AB204 at 2 weeks; however, AB204 resulted in a greater bone volume at 4 weeks, achieving the highest values recorded. No significant differences were found between the CM/BMP2 and CM/AB204 groups at either time point (P>0.05). On histological examination, new bone formation was evident in both CM/BMP2 and CM/AB204 groups. CONCLUSIONS: Within the limitations of this study, the findings indicate that AB204 may enhance osteogenic potential when used in combination with CM for bone regeneration.

Effectiveness of a collagen matrix seal and xenograft in alveolar ridge preservation: an experimental study in dogs.

Majority of previous studies on alveolar ridge preservation (ARP) used collagen membranes as barrier membranes, and further evidence for ARP in dehiscent extraction sockets with a deproteinized bovine bone mineral (DBBM) and matrix is needed. The aim of this study is to assess the impact of non-cross linked collagen membranes (membrane) and crosslinked collagen matrices (matrix) on ARP using DBBM in extraction sockets with buccal dehiscence. In six mongrel dogs, the mesial roots of three mandibular premolars (P2, P3, and P4) were extracted 1 month after dehiscence defect induction. Two experimental groups were randomly assigned: (1) DBBM with a membrane (DBBM/membrane group) and (2) DBBM with a matrix (DBBM/matrix group). Three-dimensional (3D) volumetric, microcomputed tomography (µCT), and histologic analyses were performed to assess the ridge preservation. Both groups were effective to maintain the ridge width (p > 0.05), and the DBBM/matrix group showed more favorable soft tissue regeneration and bone quality in the histological analysis (p = 0.05). Based on these results, DBBM/matrix could be better choice for ARP in cases of buccal dehiscence defects.

The cumulative survival rate of dental implants with micro-threads: a long-term retrospective study.

PURPOSE: This study aimed to evaluate the long-term cumulative survival rate (CSR) of dental implants with micro-threads in the neck over a 10-year follow-up period and to examine the factors influencing the survival rate of dental implants. METHODS: This retrospective study was based on radiographic and dental records. In total, 151 patients received 490 Oneplant® dental implants with an implant neck micro-thread design during 2006-2010 in the Department of Periodontology of Seoul National University Dental Hospital. Implant survival was evaluated using Kaplan-Meier analysis. Cox proportional hazard regression analysis was used to identify the factors influencing implant failure. RESULTS: Ten out of 490 implants (2.04%) failed due to fixture fracture. The CSR of the implants was 97.9%, and no significant difference was observed in the CSR between external- and internal-implant types (98.2% and 97.6%, respectively, P=0.670). In Cox regression analysis, 2-stage surgery significantly increased the risk of implant failure (hazard ratio: 4.769, P=0.039). There were no significant differences in influencing factors, including sex, age, implant diameter, length, fixture type, location, surgical procedure, bone grafting, and restoration type. CONCLUSIONS: Within the limitations of this retrospective study, the micro-thread design of the implant neck was found to be favorable for implant survival, with stable clinical outcomes.

The cumulative survival rate of sandblasted, large-grit, acid-etched dental implants: a retrospective analysis.

PURPOSE: This retrospective study aimed to assess the long-term cumulative survival rate of titanium, sandblasted, large-grit, acid-etched implants over a 10-year follow-up period and investigate the factors affecting the survival rate and change in marginal bone loss (MBL). METHODS: The study included 400 patients who underwent dental implant placement at the Department of Periodontology of Seoul National University Dental Hospital (SNUDH) between 2005 and 2015. Panoramic radiographic images and dental records of patients were collected and examined using Kaplan-Meier analysis, Cox proportional hazards regression analysis, and multiple regression analysis to determine the survival rates and identify any factors related to implant failure and MBL. RESULTS: A total of 782 implants were placed with a follow-up period ranging from 0 to 16 years (mean: 8.21±3.75 years). Overall, 25 implants were lost, resulting in a cumulative survival rate of 96.8%. Comparisons of the research variables regarding cumulative survival rate mostly yielded insignificant results. The mean mesial and distal MBLs were 1.85±2.31 mm and 1.59±2.03 mm, respectively. Factors influencing these values included age, diabetes mellitus (DM), jaw location, implant diameter, bone augmentation surgery, and prosthetic unit. CONCLUSIONS: This study found that the implant survival rates at SNUDH fell within the acceptable published criteria. The patients' sex, age, DM status, implant location, implant design, implant size, surgical type, bone augmentation, and prosthetic unit had no discernible influence on long-term implant survival. Sandblasted, large-grit, acid-etched implants might offer advantages in terms of implant longevity and consistent clinical outcomes.

Gingival biotype modification with collagen matrix or autogenous subepithelial connective tissue graft: Histologic and volumetric analyses in a beagle model.

Objectives: To evaluate the volumetric effect and biocompatibility of porcine tendon-derived type I collagen matrix graft (CG) in gingival biotype modification (GBM) compared with subepithelial connective tissue graft (SCTG) in a beagle model. Methods: Surface analysis using scanning electron microscopy and a collagen degradation assay of CG was performed in vitro. Six adult dogs were used in in vivo experiment, and each received autologous SCTG or CG at the anterior side. Histometric and three-dimensional digital volume analyses were conducted to compare quantitative changes in CG and SCTG in GBM. Immunohistochemical analysis was performed for the qualitative evaluation of CG compared to SCTG. Results: CG had a double-layered structure, and its degradation was slower than that of other well-reported materials. No critical problems were associated with the healing procedure. Changes in gingival thickness and volume in the CG and SCTG groups were equivalent, with no significant differences between the groups. Type I collagen and vascular endothelial growth factor expression levels were similar in both groups. Significance: CG and SCTG had equivalent potential for GBM in terms of quantity and quality. Additionally, CG could be used as a reasonable substitute for SCTG, making surgery convenient and predicting successful clinical outcomes.

A retrospective study of the long-term survival of RESTORE® dental implants with resorbable blast media surface.

PURPOSE: The aim of this study was to retrospectively evaluate the survival and failure rates of RESTORE® implants over a follow-up period of 10-15 years at a university dental hospital and to investigate the factors affecting the survival rate of these dental implants. METHODS: A total of 247 RESTORE® dental implants with a resorbable blast media (RBM) surface inserted in 86 patients between March 2006 and April 2011 at the Department of Periodontology of Seoul National University Dental Hospital were included. Patients with follow-up periods of less than 10 years were excluded, and data analysis was conducted based on dental records and radiographs. RESULTS: Over a 10- to 15-year period, the cumulative survival rate of the implants was 92.5%. Seventeen implants (6.88%) were explanted due to implant fracture (n=10, 4.05%), peri-implantitis (n=6, 2.43%), and screw fracture (n=1, 0.4%). The results of univariate regression analysis using a Cox proportional hazards model demonstrated that implants placed in male patients (hazard ratio [HR], 4.542; 95% confidence interval [CI], 1.305-15.807; P=0.017) and implants that supported removable prostheses (HR, 15.498; 95% CI, 3.105-77.357; P=0.001) showed statistically significant associations with implant failure. CONCLUSIONS: Within the limitations of this retrospective study, the RESTORE® dental implant with an RBM surface has a favorable survival rate with stable clinical outcomes.

Effects of adjacent periodontitis on osseointegrated dental implants.

PURPOSE: This study aimed to investigate whether new-onset periodontitis or apical periodontitis in the adjacent teeth affects osseointegrated dental implants in a beagle dog model. METHODS: One control group and 2 experimental groups (periodontitis and apical periodontitis groups) were defined based on the presence of experimental periodontitis or apical periodontitis, with 1 beagle dog randomly assigned to each group. The mandibular second and fourth premolars on both sides of the 3 beagles were extracted. Eight weeks after extraction, 4 bone-level implant fixtures, 2 on both sides of each mandible, were placed in each beagle. Six weeks after implant surgery, healing abutments were connected. After sufficient osseointegration, plaque control was performed in the control group, while periodontitis and apical periodontitis were induced in the experimental groups. The beagles were euthanized for histological analyses 20 weeks after induction of experimental periodontitis. Statistical analyses were performed using the Kruskal-Wallis test with the Bonferroni correction to compare the 3 groups. RESULTS: The implants in the control and apical periodontitis groups were well-maintained, while those in the periodontitis group showed clinical signs of inflammation with bone resorption. The bone-to-implant contact (BIC) and bone area values in the periodontitis group were lower than those in the other groups. The distance between the implant shoulder and the first BIC was significantly greater in the periodontitis group than in the control group (P<0.05). CONCLUSIONS: The presence of periodontitis in adjacent teeth can pose a risk to dental implants, potentially resulting in peri-implantitis. However, this was not observed for apical periodontitis. Within the limitations of this study, periodontal care is necessary to reduce the impact of periodontitis in adjacent teeth on osseointegrated implants.

Effect of a multichannel oral irrigator on periodontal health and the oral microbiome.

Oral biofilms or dental plaques are one of the major etiological factors for diverse oral diseases. We aimed to evaluate the effect of a multichannel oral irrigator (MCOI) on periodontal health in 29 participants randomly divided into two groups: the MCOI group and the control group. To evaluate the effect of the MCOI on periodontal health, the modified Quigley Hein Plaque Index (PI), Mühlemann-Son Sulcus Bleeding Index (SBI), bleeding on probing (BOP), and swelling were evaluated and compared before and after MCOI use for 3 days. Although PI and SBI showed statistically significant increases in the control group, the MCOI group showed no significant changes in either parameter. Moreover, the percentage of BOP was significantly lower in the MCOI group. Saliva samples were analyzed by 16s rRNA amplicon sequencing to investigate changes in the oral microbiome. Sequencing results showed that Porphyromonas spp. were significantly increased in the control group, whereas no significant change was detected in the MCOI group. Using the MCOI, enriched populations and functional pathways were detected in pioneer species comprising non-mutans streptococci. These findings provide evidence of the effectiveness of the MCOI in maintaining periodontal health and a healthy microbial ecology in the oral cavity.

The worldwide patent landscape of dental implant technology.

In an aging society, quality of life improvement is emerging as an important issue, and as implants are accepted as the core of oral rehabilitation treatment, competition for leadership in developing related technologies is intensifying. In this trend, unlike what is evident in the literature, the patent landscape shows the status of industrial-based technology development. A database analysis of a total of 32,237 dental implant patents shows improvements in technology, diverse geographical characteristics, and new advances toward technological convergence in this field. Technologically, dental implant technology has shown a tendency to develop from conventional implant materials and surface treatment technologies to new material technologies making use of substances such as pure zirconium and tantalum or software technologies related to diagnosis and prognosis. Regionally, dental implant technology, which was developed mainly in Europe and the Unites States in the past, is growing explosively in East Asian countries accompanied by the recent growth of the Asian market. In summary, dental implant technology seems to be developing while trying to converge with various technological areas based on the local market environment. Therefore, it is necessary to develop a new dental implant material technology that is highly applicable to the development of hybrid information/communication technology and is suitable for a new manufacturing method. Our study may provide important information to help basic and translational researchers and their financial supporters set their research directions in advancing the development of dental implants.

Dental-derived cells for regenerative medicine: stem cells, cell reprogramming, and transdifferentiation.

Embryonic stem cells have been a popular research topic in regenerative medicine owing to their pluripotency and applicability. However, due to the difficulty in harvesting them and their low yield efficiency, advanced cell reprogramming technology has been introduced as an alternative. Dental stem cells have entered the spotlight due to their regenerative potential and their ability to be obtained from biological waste generated after dental treatment. Cell reprogramming, a process of reverting mature somatic cells into stem cells, and transdifferentiation, a direct conversion between different cell types without induction of a pluripotent state, have helped overcome the shortcomings of stem cells and raised interest in their regenerative potential. Furthermore, the potential of these cells to return to their original cell types due to their epigenetic memory has reinforced the need to control the epigenetic background for successful management of cellular differentiation. Herein, we discuss all available sources of dental stem cells, the procedures used to obtain these cells, and their ability to differentiate into the desired cells. We also introduce the concepts of cell reprogramming and transdifferentiation in terms of genetics and epigenetics, including DNA methylation, histone modification, and non-coding RNA. Finally, we discuss a novel therapeutic avenue for using dental-derived cells as stem cells, and explain cell reprogramming and transdifferentiation, which are used in regenerative medicine and tissue engineering.

Dental implant proximity to adjacent teeth: A retrospective study.

BACKGROUND AND PURPOSE: The purpose of this study was to assess the occurrence and prognosis of dental implant proximity or direct contact with the adjacent tooth and to evaluate the symptoms and complications in both the implant and the adjacent tooth. We then elaborate on treatment modalities and discuss the prevention of this phenomenon. MATERIALS AND METHODS: This retrospective study was conducted based on the dental clinical and radiographic records of 43 patients with implant-tooth proximity of <1.0 mm or direct implant-tooth contact. Multivariate Bayesian logistic regression was performed to examine the influence of individual variables on correcting major clinical variables. RESULTS: In the multivariate regression analysis, the rate of occurrence of tooth symptom decreased by about 95% with every increase of 1.0 mm distance between implant and tooth (odds ratio [OR] = 0.1, 95% confidence interval [CI]: 0.004-0.680, p = 0.024). In the case of implant-tooth root proximity in the anterior area, the OR of peri-implantitis occurrence was 30.4-fold greater than in posterior sites (OR = 30.4, 95% CI: 1.189-785.914, p = 0.040). CONCLUSION: Implant-tooth root proximity or direct implant-tooth contact is an iatrogenic factor that causes various complications, including devitalization of the adjacent tooth and peri-implantitis. Proactive prevention with surgical stents and intra-operative periapical radiographs is needed. If proximity or contact is found during surgery, repositioning of the fixture to the correct location is recommended in order to maintain peri-implant health and prevent complications.

Long-Term Human Histologic Evaluation of Sinus Bone Augmentation and Simultaneous Implant Placement.

This study aimed to histologically and histomorphometrically evaluate osseointegration following simultaneous implant placement and maxillary sinus augmentation. Three retrospective human cases are described in which implants were placed at the maxillary sinus site augmented with deproteinized bovine bone mineral (DBBM) and later retrieved due to implant fracture after 5 to 8 years of occlusal loading. The removed implants with bone were processed for histologic evaluation, and bone-to-implant contact (BIC), bone area (BA), and mirror-image bone area (MIBA) were measured. Mature lamella bone was mainly observed, and some unabsorbed grafted bone particles remained in all cases. The measured values of BIC, BA, and MIBA in the three consecutive threads with the highest values were 86.0% to 91.2%, 65.8% to 91.9%, and 73.0% to 90.4%, respectively, and there were no signs of inflammation. Within the limits of this study, these cases demonstrate successful bone formation after maxillary sinus bone augmentation with DBBM and simultaneous implant placement.