Research
Scientific publications and clinical studies advancing implant dentistry
Immediate implant placement in infected sites using the "Roll BMP" technique: a 3-year case report with bioinformatic analysis
Alfredo Torres, Claudio Sotomayor
Abstract
Immediate implant placement (IIP) in sites with infection and buccal bone wall deficiency remains a clinical challenge. This case report introduces the “ROLL BMP” technique, a flapless regenerative approach combining absorbable collagen sponge (ACS), biphasic calcium phosphate (BCP), and recombinant human bone morphogenetic protein-2 (rhBMP-2) to achieve simultaneous buccal bone reconstruction and soft-tissue preservation in type 2 post-extraction sockets. A healthy 56-year-old female presented with a root fracture and chronic infection at tooth #21. After atraumatic extraction and debridement, a 3.5 × 12 mm INNO Sub implant (Cowellmedi, Busan, South Korea) was immediately placed. The biomaterial roll was created by layering BCP granules onto hydrated ACS, rolling it, and inserting it between the implant and soft tissue, followed by a 0.1 mL injection of rhBMP-2 at a concentration of 1.5 mg/mL (CowellBMP, Busan, South Korea). No flaps or membranes were required. Follow-ups at 3, 5, 12, 18, 24, and 36 months demonstrated excellent peri-implant soft-tissue stability, with a Pink Esthetic Score of 13 out of 14 at 36 months. Progressive trabecular bone maturation and buccal cortical reconstruction were also observed on CBCT. In silico bioinformatic analysis identified BMP2, RUNX2, SPP1, and BGLAP as key osteogenic hub genes involved in bone repair and osseointegration, supporting the biological rationale for this approach. In conclusion, the “ROLL BMP” technique may enable predictable flapless IIP in compromised sockets while preserving both hard and soft tissues.
Clinical Application of rhBMP-2 and Three-Dimensinal Preformed Titanium Mesh with Allograft and Xenograft for Peri-Implant Horizontal and Vertical Bone Augmentation–A Narrative Review with Technical Report
Yeong Wook Kim, Saverio Cosola, Young Sam Kim, Young Min Park, Ugo Covani, Aimone Fabbri, Giovanni Battista Menchini-Fabris
Abstract
The reconstruction of severely resorbed alveolar bone remains a significant challenge in dental implantology and maxillofacial surgery. Traditional bone grafting materials, including autogenous, allogeneic, xenogeneic, and alloplastic materials, have limitations such as donor site morbidity, limited availability, and prolonged maturation periods. To address these challenges, recombinant human bone morphogenetic protein-2 (rhBMP-2) has emerged as a potent osteoinductive factor that facilitates bone regeneration without the need for additional donor-site surgery. This study introduces a box technique that combines rhBMP-2 (CowellBMP®, Cowellmedi, Busan, Republic of Korea) with a 3D-preformed titanium mesh (3D-PFTM), using a mixture of allograft and xenograft materials for horizontal and vertical alveolar ridge augmentation. The technique leverages the structural stability provided by OssBuilder® (Osstem, Seoul, Republic of Korea), a preformed titanium mesh that allows simultaneous implant placement and vertical ridge augmentation. This approach not only reduces treatment time compared with traditional methods but also minimizes postoperative discomfort by eliminating the need for autogenous bone harvesting. Clinical outcomes demonstrated successful bone regeneration within a shorter period than previously reported techniques, with excellent bone quality and implant stability observed just four months after vertical augmentation. In conclusion, the so-called BOXAM technique — BMP-2, OssBuilder, Xenograft, Allograft, and Maintenance — presents a promising therapeutic strategy for alveolar bone reconstruction, particularly in cases of severe bone resorption. Further studies are needed to evaluate the long-term outcomes and potential limitations of this approach, especially in cases where proximity to the inferior alveolar nerve may complicate implant placement.
Bone regeneration in ceramic scaffolds with variable concentrations of PDRN and rhBMP-2
Ho-Kyung Lim, Yeh-Jin Kwon, Seok-Jin Hong
Abstract
This study evaluated the bone regeneration capacity and mechanical properties of block-type hydroxyapatite/tricalcium phosphate (HA/TCP) scaffolds in response to different concentrations of polydeoxyribonucleotide (PDRN) and recombinant human bone morphogenetic protein-2 (rhBMP-2). Thirty-two male white rabbits were used as a calvarial bone defect model and classified into eight groups according to the type and concentration of the administered growth factor: the control group, which received only the HA/TCP scaffold; scaffold + PDRN groups at 0.1, 1, 5, and 10 mg/mL; and scaffold + rhBMP-2 groups at 0.01, 0.05, and 0.1 mg/mL. The specimens were evaluated using histomorphometric and radiological analyses. Histomorphometric analysis showed that PDRN administration did not increase bone formation. However, significant increases in bone formation were observed at 8 weeks with rhBMP-2 administration at 0.05 and 0.10 mg/mL compared with the control group (p < 0.05). Radiological analysis revealed a significant increase in bone formation at 8 weeks with PDRN at 5 and 10 mg/mL and rhBMP-2 at 0.05 and 0.10 mg/mL compared with the control group (p < 0.05). These findings indicate that block-type HA/TCP scaffolds have sufficient mechanical strength and bone regeneration capacity when used with optimal concentrations of growth factors.
Full mouth rehabilitation using alveolar ridge splitting technique with immediate implant placement on maxilla and delayed implant placement on mandibula: a case report
Houssam Abou Hamdan
Abstract
The bone split procedure is a technique that is used to increase the width of narrow ridge with possible simultaneous implant placement with high success rates (98 - 100%). In that report, a 52-year-old patient with bilateral edentulous posterior mandibular ridges and edentulous maxilla was referred to our office for implant treatment. A two-step technique on mandible and immediate implant placement on maxilla was adopted. A successful prosthetic rehabilitation was done following the healing phase. This approach leads to restoration of function with a predictable outcome.
Clinical Application of DDM/rhBMP-2 in Implant Dentistry
In-Woong Um, Young-Kyun Kim, Pil-Young Yun, Zi-Yu Yan, Yu-Mi Kim
Abstract
Recombinant human bone morphogenetic protein-2 (rhBMP-2) is a well-known osteoinductive growth factor that can be used with various carriers. Demineralized dentin matrix (DDM), which has both osteoinductive and osteoconductive capacities, has been developed as a potential carrier for rhBMP-2. DDM contains endogenous growth factors and fulfills key requirements for an ideal carrier, including controlled release kinetics, biocompatibility, biodegradability, and bone-forming capacity. DDM loaded with rhBMP-2 (DDM/rhBMP-2) has been evaluated through in vitro and in vivo studies to verify its clinical safety and efficacy. Recent clinical trials and outcomes in Korea have also demonstrated that DDM/rhBMP-2 is safe and effective in implant dentistry, particularly in terms of enhanced bone formation, remodeling capacity, and the use of a reduced concentration of rhBMP-2. This chapter introduces the clinical application of DDM/rhBMP-2 in implant dentistry, based on related experimental and clinical research.
Controlled release of BMP-2 using a heparin-conjugated carrier system reduces in vivo adipose tissue formation
Jung-Seok Lee, Sun-Kyoung Lee, Byung-Soo Kim, Gun-Il Im, Kyoo-Sung Cho, Chang-Sung Kim
Abstract
There is growing concern about unwanted effects associated with the clinical use of recombinant human bone morphogenetic protein-2 (rhBMP-2) at high concentrations, including cyst-like bone formation and excessive fatty marrow formation. Therefore, we evaluated mineralized and adipose tissue formation, as well as the bone-healing pattern, associated with the controlled release of E. coli-derived rhBMP-2 (ErhBMP-2) using a heparin-conjugated fibrin (HCF) system in ectopic and orthotopic in vivo models. In the ectopic transplantation model, mineralized tissue formed at the most superficial layer of the transplanted area and on the surfaces of the grafted materials. Most of the interstitial space within the transplanted area was filled with excessive adipose tissue, specifically at sites that received ErhBMP-2. However, sites treated with ErhBMP-2 and HCF showed significantly increased mineralized tissue formation and decreased adipose tissue formation compared with sites treated with ErhBMP-2 and a normal fibrin system. In the orthotopic calvarial defect model, HCF-mediated controlled release of ErhBMP-2 significantly reduced adipose tissue formation within the defect area compared with the clinically approved absorbable collagen sponge. These results suggest that an HCF system loaded with ErhBMP-2 may reduce adipose tissue formation and enhance mineralized tissue formation.
Comparison of collagen membrane and bone substitute as a carrier for rhBMP-2 in lateral onlay graft
Yun Young Chang, Jung Seok Lee, Min Soo Kim, Seong-Ho Choi, Jung-Kiu Chai
Abstract
Objectives To evaluate the bone regenerative effect of bioresorbable collagen membrane (CM) as a carrier for recombinant human bone morphogenetic protein-2 (rhBMP-2) when performing lateral onlay grafts using bovine hydroxyapatite incorporated with collagen matrix (BHC) in combination with CM in dogs. Material and methods A guided bone regeneration (GBR) was performed at the buccal aspect of edentulous maxillary alveolar ridges in dogs (n = 5): (1) BHC group, in which rhBMP-2-loaded BHC was covered by a CM, and (2) CM group, in which BHC was covered by an rhBMP-2-loaded CM. A histologic and histometric analysis was performed after 8 weeks of healing. Results Both the BHC and CM groups exhibited substantial newly formed bone (NB). More NB was found in the CM group than in the BHC group without statistical significance. Most of the NB was in direct contact with the residual bone substitute in the BHC group, whereas the projections and islands of NB were observed in the spaces between the residual bone substitute clusters in the CM group. The bone-to-residual bone substitute contact ratio was significantly lower in the CM group than in the BHC group (P = 0.043). Conclusions Within the limitations of this study, it can be concluded that rhBMP-2-loaded CM performed lateral onlay grafts as effectively as rhBMP-2-loaded BHC while showing less bone-residual bone substitute contact ratio in dogs. The loading of CMs with rhBMP-2 might therefore be a recommendable treatment option for facilitating lateral onlay graft combined with rhBMP-2.
Prospective randomized, controlled trial of sinus grafting using Escherichia coli-produced rhBMP-2 with a biphasic calcium phosphate carrier compared to deproteinized bovine bone
Min-Soo Kim, Jung-Seok Lee, Hyun-Ki Shin, Jae-Shin Kim, Jeong-Ho Yun, Kyoo-Sung Cho
Abstract
Aim: This study compared the effects of Escherichia coli-produced recombinant human bone morphogenetic protein-2 (ErhBMP-2) with a biphasic calcium phosphate (BCP) carrier to those of deproteinized bovine bone in human maxillary sinus floor augmentation. Materials and methods: Screening for this clinical trial identified 56 sites from patients who provided informed consent to participate. Of these, 46 sites were ultimately enrolled, and 41 were finally included in the study. The sites were divided into two groups using a random-number table, and the respective materials were applied. A trephine biopsy was performed after 24 weeks, followed by implant placement using implants wider than the biopsy site. Computed tomography and plain panoramic images were obtained immediately after surgery and again at 24 weeks. The radiographic images were reconstructed to measure linear and volumetric changes. The biopsy samples were processed for histologic and histometric analyses. Results: All sites healed uneventfully, with no complications. Radiographic analysis showed a tendency toward volume increase, but the difference was not statistically significant in either group. Comparison of volumetric changes between the two groups also revealed no significant difference. In addition, none of the histometric parameters differed significantly between the groups, although different healing patterns were observed on histologic analysis. Conclusions and clinical implications: Sinus augmentation using ErhBMP-2 with a BCP carrier did not enhance bone regeneration compared with conventional treatment using deproteinized bovine bone at 24 weeks after surgery.
Vertical Regeneration with rhBMP-2 bone graft Versus INNO™ Implants with 5.5-mm Short Intrabony Length in Atrophic Posterior Mandibles
Dae-Kyung Kim
Abstract
Purpose: To retrospectively compare the outcomes of implants placed in posterior mandibles vertically regenerated with rhBMP-2 bone grafts and short dental implants. Methods: Consecutive patients with vertical bone atrophy in edentulous mandibular posterior regions (6 to 8 mm of bone above the inferior alveolar nerve) were treated with either implants placed in regenerated bone using rhBMP-2 bone graft or short INNO™ implants (with 4.0-mm intrabony length) in native bone between 2011 and 2013 and followed for 12 months after loading. Panoramic radiographs were obtained from each patient as follows: before surgery, immediately after implant placement, 6 months after surgery, and after 1 year. Clinical and radiographic examinations were performed at every visit. Results: All of 3 implants at group 1 and 6 implants at group 2 were stable functionally, as well as clinically and radiographically, during the follow-up. No infection occurred in all sites, and all implants succeeded in the observation follow-up period. There was a 100% survival rate of implant in both groups, the same as in intact mandibular posterior ridge. Conclusions: When residual bone height over the mandibular canal is between 6 and 8 mm, short implants (with 4.0-mm intrabony length) might be a preferable treatment option over vertical augmentation, reducing chair time, expense, and morbidity.
Marginal bone change of Immediate Versus Delayed Restoration Procedures on Immediate Implants in Single Tooth Replacement
Duk-Sang Jang
Abstract
Purpose: The primary aim of this study was to evaluate and compare the overall clinical outcomes of immediate and delayed restoration procedures for implants placed in fresh extraction sockets by means of a flapless technique and rhBMP-2 bone graft. Materials and Methods: A total 30 dental implants were evaluated in 30 patients (14 male and 16 female) with an average age of 46.2 years. All patients underwent tooth extraction and clinical measurements at baseline; the amount of available alveolar bone and the presence of an intact buccal bone wall were evaluated. Implants with an insertion torque of at least 45 N cm were included in the immediate restoration group and were temporarily restored immediately after implant placement; on the other hand, implants with an insertion torque lower than 45 N cm were included in the delayed restoration group and were restored 4 months after implant placement. Patient data were evaluated to acquire implant survival rates and the marginal bone change. Panoramic X-rays were analyzed for marginal bone loss. Results: Any implant among 30 INNO® dental implants of both 15 immediate restoration group and 15 delayed restoration group was not lost, resulting in a survival rate of 100 %. In marginal bone change, immediate loading (0.18 ± 0.01 mm) was not a factor of bone loss, compared with delayed loading (0.26 ± 0.19 mm). Conclusions: Immediate restoration of implants installed in fresh extraction sockets was at least as effective and safe as delayed restoration.
Clinical Case Reports of INNO SLA Hydrophilic Implant
Xavier Roca Mompel
Abstract
Objective The aim of the report is to evaluate the result of success rate of INNO SLA hydrophilic implant. Method Of the 153 patients who received 318 implants of the INNO SLA Implant System from July 2012 to February 2014. 132 patients with 278 implants were recalled after implantation for quarterly clinical examination and check. 125 implants on 52 patients out of 132 patients were immediately loaded with temporary restoration and completely done with final restoration from 6weeks to 10weeks later or with final restoration, 104 implants on 60 patients were early loaded within 6 weeks from the date of being placed, and staged implantation which allows healing period for more than 12weeks was implemented to 20 patients with 49 implants. Conclusion Although bone grafting was done to 97 of 132 patients with 278 INNO SLA hydrophilic implant and rhBMP-2 is used for about 40% of them, success rate of INNO SLA hydrophilic implant is high in consideration of average statue of 132 patients with 278 implants and determined loading time with final restoration. 7 implants of 278 implants were failed. The success rate is 97.48%. Due to the limit of the study,it is hard to conclude that survival rate of INNO SLA hydrophilic implant is higher than other implants sold in market. It, however, could be concluded that success rate of INNO SLA hydrophilic implant is much higher compared to others placed with similar technic for the almost same period of the study.
Bone formation of middle ear cavity using biphasic calcium phosphate lyophilized with Escherichia coli-derived recombinant human bone morphogenetic protein 2 using animal model
Sung Eun Kim, Young-Pil Yun, Hae-Ryong Song, Kyung-Hee Choi, Bo Hae Kim, Eun Kyeung Lee, Jae-Jun Song
Abstract
Objective The aim of the study was to analyze the value of Escherichia coli-derived recombinant human bone morphogenetic protein-2 (ErhBMP-2) coated biphasic calcium phosphate (BCP) for the obliteration of middle ear bone defect after mastoid surgery. Methods Twenty-four specific pathogen-free Sprague-Dawley rats were randomly assigned to the BCP group (n = 12) and BCP-ErhBMP-2 group (n = 12; in which BCP scaffold of the granular type was coated with ErhBMP-2). In both groups, BCP scaffold was used to surgically fill the middle ear bulla. New bone formation was evaluated by measuring bone density (%) after 4 and 8 weeks in all rats in both groups. Results At 4 weeks, new bone was visible at the periphery and center of the middle ear cavity in both groups. In the BCP group, a moderate amount of fibrous tissue had infiltrated into the interspace of the scaffolds. New bone almost totally filled the interspace in the BCP-ErhBMP-2 group. At 8 weeks, copious new bone formation had occurred. Histometric measurements showed that bone density in the BCP group was smaller than in the BCP-ErhBMP-2 group at 4 weeks (25.10% and 38.43%, respectively; p < 0.05) and 8 weeks (25.54% and 34.18%, respectively; p < 0.05). Conclusions New bone formation was greater in the presence of BCP-ErhBMP-2 scaffolds. ErhBMP-2 coated BCP scaffolds is a potentially useful material for middle ear obliteration after mastoidectomy.
Sinus floor elevation with simultaneous placement of INNO™ implants: a 1-year radiographic evaluation
Dae-Hee Lee
Abstract
Purpose: This study evaluated the clinical results of submerged INNO implants placed at the time of the sinus floor elevation procedure at sites where native bone height was less than 4 mm. Changes in graft height were also assessed using radiographs for 1 year after the implant procedure. Methods: The sinus floor elevation procedure with rhBMP-2 bone graft was performed on 4 patients with atrophic posterior maxillas with simultaneous placement of 7 submerged INNO implants. Panoramic radiographs were obtained from each patient as follows: before surgery, immediately after implant placement, 6 months after surgery, and after 1 year. Clinical and radiographic examinations were performed at every visit. Radiographic changes in graft height were calculated with respect to the implant’s known length and the original sinus height. Results: All implants were stable functionally, as well as clinically and radiographically, during the follow-up. Most of the radiographic reduction in the grafted bone height occurred in the first 6 months; reduction after 6 months was slight. Conclusions: The simultaneous placement of submerged INNO implants using sinus floor elevation procedure with rhBMP-2 is a feasible treatment option for patients with severe atrophic posterior maxillas.
Survival rate of INNO™ implants placed in the site of sinus membrane perforation
Dae-Hee Lee
Abstract
Purpose: This study evaluated the survival rate of INNO implants placed simultaneously in the site of sinus membrane perforation at the time of the sinus floor elevation procedure at sites where native bone height was more than 4 mm. Methods: Sinus membrane perforations were detected in 4 patients, and 6 INNO implants were inserted in 4 sinus sites with simultaneous placement. Panoramic radiographs were obtained from each patient as follows: before surgery, immediately after implant placement, 6 months after surgery, and after 1 year. Clinical and radiographic examinations were performed at every visit. Results: All implants were stable functionally, as well as clinically and radiographically, during the follow-up. No infection occurred in all sites, and all implants succeeded in the observation follow-up period. There was a 100% survival rate of implant in perforated sinuses, the same as in intact sinuses. Conclusions: Perforation of the sinus membrane does not compromise the short-term survival of INNO implants placed in combination with the crestal approach of sinus bone augmentation.
Recombinant Human Bone Morphogenetic Protein-2 Stimulates the Osteogenic Potential of the Schneiderian Membrane: A Histometric Analysis in Rabbits
Youna Choi, Jung-Seok Lee, Yu-Jin Kim
Abstract
This study evaluated the osteoinductive effect of a recombinant human bone morphogenetic protein-2 (rhBMP-2)-coated biphasic calcium phosphate (BCP) carrier system in the grafted sinus area, including the surrounding tissues and Schneiderian membrane. A total of 18 male rabbits were used in this study: two for in vitro experiments and 16 for in vivo experiments. Schneiderian membranes obtained from two animals were cultured with or without rhBMP-2, and quantitative reverse transcription-polymerase chain reaction analysis was performed. Both maxillary sinuses in each of the 16 animals were used to compare the in vivo effects of rhBMP-2-coated BCP, used as the experimental group, and BCP alone, used as the control group. In each animal, rhBMP-2-coated BCP was grafted into one maxillary sinus, while the same amount of BCP alone was grafted into the contralateral sinus in a randomized order. Radiologic and histometric analyses were performed at 2 and 8 weeks after surgery. After 2 days of culture with or without rhBMP-2, a significant increase in the expression of early osteoblast markers, including RUNX2, type I collagen, alkaline phosphatase, and osteopontin, was observed. Different histologic healing patterns were noted between the experimental and control sites. At the experimental sites, newly formed bone was mainly observed along the reflected sinus membrane, with little to no bone formation in the central area (window = 0.06%; center = 0%; membrane = 20.86% new bone). In contrast, the control sites showed evenly distributed new bone formation (window = 7.27%; center = 7.41%; membrane = 15.58% new bone). The augmented volume was well maintained at both the experimental and control sites throughout the experimental period. However, at 2 weeks, the augmented volume was significantly greater at the experimental sites than at the control sites (232.62 and 195.29 mm³, respectively; p < 0.001). These results suggest that BCP provides good space maintenance in sinus augmentation, while rhBMP-2 activates the osteoinductive potential of the sinus membrane during the early stage of healing.
The effect of anodized implants coated with combined rhBMP-2 and recombinant human vascular endothelial growth factors on vertical bone regeneration in the marginal portion of the peri-implant
Jong Eun Kim, Seong Su Kang, Kyung Hee Choi, June Sung Shim, Chang Mo Jeong, Sang Wan Shin, Jung Bo Huh
Abstract
Objectives The aim of this study was to evaluate the effect of anodized implants coated with combined rhBMP-2 and recombinant human vascular endothelial growth factors (rhVEGFs) on vertical bone regeneration in the marginal portion of the peri-implant. Study Design Supra-alveolar defects were created in 3 male beagle dogs. Each animal received 8 implants that were either coated with a single growth factor (rhBMP-2) or combined growth factors (rhBMP-2 + rhVEGF), or an anodized implant (the control group). The amount of the vertical bone regeneration, the bone-implant contact, and the intrathread bone density were investigated using histomorphometric analysis at 8 weeks. Results The bone morphogenetic protein (BMP) group and the BMP-VEGF group showed vertical alveolar bone regeneration and enhanced bone-implant contact in the microthread compared with the control group (P < .05). Conclusions Anodized implants coated with rhBMP-2 and rhBMP - 2 + rhVEGF can induce vertical alveolar bone regeneration, but the combined effect of rhBMP-2 and rhVEGF was not verified.
Bone Formation and Remodeling of Three Different Dental Implant Surfaces with Escherichia Coli–Derived Recombinant Human Bone Morphogenetic Protein 2 in a Rabbit Model
Jae-Kwan Lee, Lee-Ra Cho, Heung-Sik Um
Abstract
Purpose: The objective of this study was to analyze orthotopic bone formation and remodeling around three different dental implant surfaces, with or without recombinant human bone morphogenetic protein-2 derived from Escherichia coli (ErhBMP-2), in a rabbit model. Materials and Methods: Resorbable blasting media (RBM), sandblasted, large-grit, acid-etched (SLA), and magnesium-incorporated oxidized (MgO) implant surfaces were coated with ErhBMP-2 at a concentration of 1.5 mg/mL. The implants were placed in the proximal tibiae of six New Zealand White rabbits. Each rabbit received six different implants: three ErhBMP-2-coated implants in one tibia and three uncoated implants in the contralateral tibia. The sites were closed to submerge the implants. The animals received fluorescent bone markers: alizarin at 2 weeks, calcein at 4 weeks, and tetracycline at 6 weeks. They were euthanized at 8 weeks for histomorphometric analysis. Results: The amount of ErhBMP-2 coating was 9.6 ± 0.4 µg per MgO implant, 14.5 ± 0.6 µg per RBM implant, and 29.9 ± 3.8 µg per SLA implant. Clinical healing was uneventful. The mean bone-to-implant contact (BIC) was significantly greater for ErhBMP-2/RBM implants (35.4% ± 5.1%) and ErhBMP-2/MgO implants (33.4% ± 13.2%) than for uncoated RBM implants (23.6% ± 6.2%) and MgO implants (24.9% ± 2.7%) (p < 0.05). However, when cortical bone BIC was considered, ErhBMP-2/SLA implants showed lower BIC (32.9% ± 7.8%) than all other implant variations, which ranged from 39.9% ± 18.1% to 51.3% ± 9.2% (p < 0.05). No remarkable differences were observed in new bone area, except for minor differences between implant types. Conclusions: Within the limitations of this study, the absorbed dose of ErhBMP-2 was found to vary according to implant surface characteristics, thereby influencing local bone formation and remodeling.
Retrospective study of marginal bone change in 1 year loading of INNO® dental implant
Dae-Hee Lee
Abstract
Introduction: The marginal bone change of the 1 year panoramic x-rays were evaluated in the platform switching structured INNO® dental implant of which the surface is treated with the RBM sandblasting, hyper-thermal acid etching and alkali solution cleaning process. Material and Methods: A total 114 dental implants were evaluated in 47 patients. Patient data was evaluated to acquire implant survival rates, gender, implant diameter, length, extraction socket, loading time, adjacent tooth, opposing tooth and kind of prosthesis. Panoramic X-rays were analyzed for marginal bone loss. Results: 1 year survival rate was 99.3% (1 implant lost at 1 year). A average marginal bone loss was 0.027± 0.013 mm in total 142 implants. The marginal bone loss of arches was 0.018 ± 0.007 mm in maxilla and 0.034 ± 0.032 mm in mandible (P>0.05). The bone loss of 8 mm length implant (0.025 ± 0.0009 mm) was lower than 10 mm length implant (0.033 ± 0.031 mm) without significant difference (P>0.05). Immediate implant placement (0.014 ± 0.009 mm) was lower than late placement (0.036 ± 0.024 mm) in marginal bone loss without significant difference (P>0.05). The site of periodontitis with periapical lesion (0.027 ± 0.017 mm) was the same as the other site (0.027 ± 0.019 mm) in marginal bone loss. Conclusion: Within the limitations of this study, we conclude that INNO® dental implant have equal survival rates to the others of platform switched implants. Marginal bone loss was low even in the short length implant, immediate implant placement and the socket of periodontitis with periapical lesion, compared to the other clinical results.
Survival rate and marginal bone change of INNO implants placed in augmented extraction sockets
Dae-Kyung Kim
Abstract
Background: The alveolar ridge undergoes reabsorption and atrophy subsequent to tooth removal and thus exhibits a wide range of dimensional changes. Preservation of the alveolar crest after tooth extraction is essential to enhance the surgical site before implant fixture placement. The aim of this clinical study is to investigate and compare the need for additional augmentation procedures at implant insertion, as well as the success rate and marginal bone loss for implants placed in the grafted sites versus those placed in naturally healed sites. Methods: Twenty patients with hopeless tooth were allocated to: 1) a test group, receiving extraction and grafting synthetic bone. After 4 months of healing, implants were inserted in each of the sites. and 2) a control group, receiving extraction without any graft and having intact crestal bone. The implants were submerged and loaded at conventional loading time with metal–ceramic rehabilitation. The follow-up included evaluation of implant diameter and length, the need for additional augmentation procedures at implant placement, implant failure, and marginal bone level changes. All patients were followed in 1 year. Results: The implant success rate at the 1-year follow-up visit reached 100% for both groups. No statistically significant differences were detected for marginal bone changes between the two groups. Conclusions: It was concluded that implants placed into grafted extraction sockets exhibited a clinical performance similar to implants placed into non-grafted sites in terms of implant survival and marginal bone loss. However, grafted sites allowed implant placed in the normal position of ridge when compared to naturally healed sites.
Case report using INNO implant of Hydrophilic SLA surface
Dae-Hee Lee
Abstract
Reported herein are cases involving the use of INNO implants with a hydrophilic SLA surface, which have recently been introduced by Cowellmedi. The SLA surface exhibits hydrophilic properties, with a contact angle of 90° or less immediately after production. However, the contact angle is known to increase over time, reportedly reaching up to 139°, due to hydrocarbon contamination from the air, which gradually increases surface hydrophobicity. As reported by Schwarz et al., hydrophobic surfaces show lower blood compatibility than hydrophilic surfaces, and bone-to-implant contact may be significantly reduced after healing in GBR cases involving dehiscence defects. Therefore, to achieve stable marginal bone levels even after loading in GBR cases, the use of a hydrophilic implant surface may be beneficial.
Effect of different concentrations of Escherichia coli-derived rhBMP-2 coating on osseointegration of implants in dogs
Yu-Jin Lee, Yemi Kim, Ji-Youn Kim, Jung-Bo Huh, Myung-Rae Kim, Sun-Jong Kim
Abstract
The aim of the present study was to evaluate the effect of different concentrations of Escherichia coli-derived recombinant human bone morphogenetic protein-2 (ErhBMP-2) coating on the osseointegration of implants (Cowellmedi, Busan, Korea) in dogs. Three beagle dogs were used in this study. The mandibular premolars were extracted without causing bone destruction, followed by an 8-week healing period. The implants were coated with four different concentrations of ErhBMP-2: 0.1, 0.3, 0.5, and 1.0 mg/mL. They were then placed in the healed extraction sites of the mandible, and bone formation was assessed after 8 weeks. After the dogs were euthanized, histological samples were obtained, and bone volume (BV) and bone-to-implant contact (BIC) were measured. The BV ratio was highest in the ErhBMP-2 0.3 mg/mL group; however, the differences in BV ratio among the treatment groups were not statistically significant. The BIC level was higher in the ErhBMP-2 1.0 mg/mL and 0.3 mg/mL groups than in the other groups, but the differences were also not statistically significant. In addition, the BIC level at all sites was relatively lower than that reported in previous studies. In this study, ErhBMP-2 coating on implants was not found to improve BV or BIC in healthy alveolar bone. Further studies are needed to compare BIC levels between ErhBMP-2-coated and non-coated implants.
Novel analysis model for implant osseointegration using ectopic bone formation via rhBMP-2/macroporous biphasic calcium phosphate (MBCP) system in rats
Jung-Chul Park, Jong-Bin Lee, Guy Daculsi, Sang-Yeop Oh, Kyoo-Sung Cho, Gun-Il Im, Byung-Soo Kim, Chang-Sung Kim
Abstract
The osseointegration around titanium mini-implants placed in macroporous biphasic calcium phosphate (MBCP) blocks was evaluated after incubation with recombinant human bone morphogenetic protein-2 (rhBMP-2) in an ectopic subcutaneous rat model. Mini-implants (Ø1.8 × 12 mm) were placed in MBCP blocks (bMBCPs, 4 × 5 × 15 mm) loaded with rhBMP-2 at 0.1 mg/mL. The blocks were then implanted into subcutaneous pockets of male Sprague-Dawley rats (n = 10) for 8 weeks. Histomorphometric analysis was performed to evaluate bone-to-implant contact (BIC) and bone density. Significant osteoinductive activity was observed in the rhBMP-2/bMBCP group. The BIC percentage was 41.23 ± 4.13%, and bone density was 33.47 ± 5.73%. In contrast, no bone formation was observed in the bMBCP-only group. This model provides a more standardized tool for analyzing osseointegration and bone healing along the implant surface and within bMBCPs, while excluding various healing factors derived from selected animal species and defect models.
A look into the surface composition and morphology of SLA surface treatment implant that has been recently marketed
Dae-Hee Lee
Abstract
The surface property of dental implants has been known to be a major factor of osseointegration. To enhance clinical success rates, various implant surface treatments have been tried. The method of sandblasting and thermal acid etching surface treatment (SLA) has recently been used by many dental implant manufacturers. In this study, the surface components and shapes of SLA dental implants that were produced in South Korea were compared and analyzed. Through X-ray photoelectron spectroscopy (XPS), stereo scanning electron microscopy (SEM) and surface roughness measurements, the uniformity of the sandblast and the completeness of the acid etching were examined. To confirm the surface migrations, the components of the surface eluate were analyzed using combustion ion chromatography (CIC). The analysis of the SLA implants that have been introduced in the market confirmed that all of them had a rough surface and satisfactory acid etching uniformity in both their upper and lower sections. In addition, no hazardous material that could inhibit bone regeneration was observed in their surface components and in the eluate, which confirmed that their manufacturers cleaned them excellently. Considering that Straumann’s SLA active implants had a mean roughness of 1.75 μm, Cowellmedi’s INNO SLA implants seem to have been most similar to Straumann’s SLA active implants among the specimen products.
Effects of anodized implants coated with Escherichia coli-derived rhBMP-2 in beagle dogs
Jung-Bo Huh, Sung-Eun Kim, Hyo-Eon Kim, Seong-Soo Kang, Kyung-Hee Choi, Chang-Mo Jeong, Jeong-Yol Lee, Sang-Wan shin
Abstract
This study evaluated the effects of Escherichia coli-derived recombinant human bone morphogenetic protein-2 (ErhBMP-2) coated onto anodized implants on bone formation, osseointegration, and vertical bone growth in a vertical bone defect model. Six young adult beagle dogs were used. After a 2-month bone healing period, anodized titanium implants 8 mm in length were placed 5.5 mm into the mandibular alveolar ridge. Eighteen implants coated with ErhBMP-2, referred to as the BMP group, and another 18 uncoated implants, referred to as the control group, were placed using a randomized split-mouth design. Implant stability quotient (ISQ) values were measured, and specimens were prepared for histometric analysis to evaluate osseointegration and bone formation. At 8 weeks after implant placement, ISQ values were significantly higher in the BMP group than in the control group (p < 0.05). Histological observations showed that changes in buccolingual alveolar bone levels were greater in the BMP group than in the control group (p < 0.05). These findings suggest that ErhBMP-2-coated anodized implants can stimulate bone formation and significantly increase implant stability on completely healed alveolar ridges in dogs. Further studies are warranted to evaluate the effects of ErhBMP-2 on osseointegration at the bone–implant interface.
Analysis of hydrolyzable polyethylene glycol hydrogels and deproteinized bone mineral as delivery systems for glycosylated and non-glycosylated bone morphogenetic protein-2
Patrick Hänseler, Ui-Won Jung, Ronald E. Jung, Kyoung-Hee Choi, Kyoo-Sung Cho, Christoph H.F. Hämmerle, Franz E. Weber
Abstract
Bone morphogenetic proteins (BMPs), particularly BMP-2, are growth factors primarily responsible for osteoinduction. Understanding the interactions between bone substitute materials and different growth factor variants is crucial for designing bone substitutes with an ideal release profile. In this study, we compared glycosylated and non-glycosylated recombinant human bone morphogenetic protein-2 (rhBMP-2), either incorporated into a hydrolyzable polyethylene glycol (PEG) hydrogel developed as a slow-release system or adsorbed onto deproteinized bovine bone matrix (DBBM), a clinically well-established bone substitute material. The rhBMP-2-loaded materials were immersed in cell culture medium, and rhBMP-2 concentration profiles in the supernatant were determined using an enzyme-linked immunosorbent assay. The corresponding biological activities were assessed in vitro using an alkaline phosphatase activity assay. The results showed a strong affinity of rhBMP-2 for DBBM and reduced biological activity after release from PEG hydrogels. Glycosylated rhBMP-2 was significantly less affected by the hydrogel and interacted more strongly with DBBM than non-glycosylated rhBMP-2. Therefore, the combination of PEG hydrogels with DBBM as an rhBMP-2 delivery system may be questionable compared with DBBM alone, since rhBMP-2 released from the hydrogel may become trapped by DBBM. Moreover, these results suggest that glycosylated rhBMP-2 may be favorable in combination with PEG hydrogels because its activity is better preserved, whereas non-glycosylated rhBMP-2 may be favorable in combination with DBBM due to its initially higher concentration of free rhBMP-2.
Bone formation of block and particulated biphasic calcium phosphate lyophilized with Escherichia coli-derived recombinant human bone morphogenetic protein 2 in rat calvarial defects
Jin-Woo Kim, Kyung-Hee Choi, Jeong-Ho Yun, Ui-Won Jung, Chang-Sung Kim, Seong-Ho Choi, Kyoo-Sung Cho
Abstract
The objective of this study was to evaluate bone formation in rat calvarial defects after surgical implantation of block-type or particulate biphasic calcium phosphate (BCP) lyophilized with Escherichia coli-derived recombinant human bone morphogenetic protein-2 (ErhBMP-2). Critical-size calvarial osteotomy defects were created in five groups of Sprague-Dawley rats. Each group received one of the following treatments: 1) sham surgery control; 2) biphasic calcium phosphate particles (CPP); 3) biphasic calcium phosphate block (CPB); 4) ErhBMP-2-coated CPP; or 5) ErhBMP-2-coated CPB. ErhBMP-2 was coated onto BCP using a stepwise lyophilization protocol. New bone formation was significantly greater in the ErhBMP-2-treated groups than in the untreated groups. In particular, the ErhBMP-2/CPB group showed stability of the augmented area during the healing period, owing to its relevant space-maintaining capacity. These findings suggest that CPP and CPB lyophilized with ErhBMP-2 enhance new bone formation, and that CPB may be a suitable carrier for ErhBMP-2 when three-dimensional structural integrity is an important consideration.
Randomized clinical trial on the efficacy of Escherichia coli-derived rhBMP-2 with β-TCP/HA in extraction socket
Jung-Bo Huh, Hyo-Jung Lee
Abstract
Purpose: This randomized clinical trial was conducted to assess the safety and effectiveness of ErhBMP-2 in alveolar bone regeneration, as well as the preservation of β-TCP/HA bone graft material containing ErhBMP-2. Materials and Methods: This study involved 72 patients from three study centers. The patients were divided into two groups: an experimental group, which received ErhBMP-2-coated β-TCP/HA, and a control group, which received β-TCP/HA graft material alone. The materials were transplanted immediately after tooth extraction. CT scans were taken before transplantation and 3 months after surgery, and the healing status was compared between the two groups. The efficacy endpoints used to evaluate the degree of bone induction included alveolar bone height and three measurements of bone width. A paired t-test was used to determine the significance of the changes (p < 0.05). Results: Changes in alveolar bone height were -1.087 ± 1.413 mm in the control group and -0.059 ± 0.960 mm in the experimental group (p < 0.01). At 25% extraction socket length (ESL), the changes in bone width were 0.006 ± 1.149 mm in the control group and 1.279 ± 1.387 mm in the experimental group. At 50% ESL, the changes were 0.542 ± 1.157 mm and 1.239 ± 1.249 mm, respectively. The differences were statistically significant at 25% ESL (p < 0.01) and 50% ESL (p < 0.05). No adverse reactions to the graft material were observed during the study. Conclusion: ErhBMP-2-coated β-TCP/HA was found to be more effective in preserving alveolar bone than conventional β-TCP/HA alloplastic bone graft material.
The effect of immobilization of heparin and bone morphogenic protein-2 to bovine bone substitute on osteoblast-like cell’s function
Jung-Bo Huh, Sung-Eun Kim, Se-Kyung Song, Mi-Jung Yun, Ji-Suk Shim, Jeong-Yol Lee, Sang-Wan Shin
Abstract
Purpose: This study was performed to investigate whether recombinant human bone morphogenetic protein-2 (rhBMP-2), immobilized on a heparin-grafted bone substrate, could enhance osteoblastic functions. Materials and Methods: Bio-Oss® without any coating material was used as the control group. In the rhBMP-2-Bio-Oss® group, rhBMP-2 was coated onto Bio-Oss® using a dip-and-dry method at a concentration of 50 ng/mL for 24 hours. In the heparinized rhBMP-2-Bio-Oss® group, dopamine was anchored to the surface of Bio-Oss®, followed by heparin coating. rhBMP-2 was then immobilized onto the heparinized Bio-Oss® surface. The release kinetics of rhBMP-2 from the rhBMP-2-Bio-Oss® and heparinized rhBMP-2-Bio-Oss® groups were analyzed using an enzyme-linked immunosorbent assay. The biological activities of MG63 cells in the three groups were investigated using a cytotoxicity assay, cell proliferation assay, alkaline phosphatase (ALP) activity measurement, and calcium deposition analysis. Statistical comparisons were performed using one-way ANOVA, and differences were considered statistically significant at *p < 0.05 and **p < 0.001. Results: Heparinized rhBMP-2-Bio-Oss® showed more sustained release than rhBMP-2-Bio-Oss® over an extended period. In the ALP activity measurement, the heparinized group showed significantly higher ALP activity than the non-heparinized groups (p < 0.05). MG63 cells cultured in the rhBMP-2-containing groups showed increased calcium deposition, with the heparinized group showing a greater increase than the non-heparinized groups. Conclusion: Heparin increased the amount and duration of rhBMP-2 release, enabling sustained release. Heparinized Bio-Oss® with rhBMP-2 successfully improved osteoblastic functions.
Discontinuous Release of Bone Morphogenetic Protein-2 Loaded Within Interconnected Pores of Honeycomb-Like Polycaprolactone Scaffold Promotes Bone Healing in a Large Bone Defect of Rabbit Ulna
Ji-Hoon Bae, Hae-Ryong Song, Hak-Jun Kim, Hong-Chul Lim, Jung-Ho Park, Yuchun Liu, Swee-Hin Teoh
Abstract
The choice of an appropriate carrier and its microarchitectural design is integral to directing bone ingrowth into the defect site and determining the subsequent rate of bone formation and remodeling. We selected a three-dimensional polycaprolactone (PCL) scaffold with an interconnected honeycomb-like porous structure to provide a conduit for vascular ingrowth, as well as an osteoconductive pathway to guide recruited cells responding to the unique triphasic release of osteoinductive bone morphogenetic proteins (BMPs) from the PCL scaffold. We hypothesized that recombinant human bone morphogenetic protein-2 (rhBMP-2)-PCL constructs would promote rapid union and bone regeneration in large defects. The results of our pilot study using a unilateral 15 mm mid-diaphyseal segmental rabbit ulna defect demonstrated enhanced bone healing, with greater bone formation and bridging on plain radiography and microcomputed tomography compared with the empty PCL and untreated groups at 8 weeks after implantation. Quantitative measurements showed significantly higher bone volume fraction and trabecular thickness, along with lower trabecular separation, in the rhBMP-2-treated groups. Histologic evaluation also revealed greater mature bone formation spanning the entire scaffold region compared with the other groups, which showed no bone regeneration within the central defect zone. These findings highlight the unique characteristics of the scaffold, particularly its highly porous network of channels, which promoted vascular integration and allowed cellular infiltration. This structure led to a discontinuous triphasic BMP-2 release profile that mimicked the release pattern observed during natural in vivo repair mechanisms. This study provides preclinical evidence supporting the potential of combining osteoinductive rhBMP-2 with PCL constructs for the repair of large bone defects in a large animal model.
Multicenter, randomized clinical trial on the efficacy and safety of Escherichia coli-derived rhBMP-2 with β-TCP and hydroxyapatite in human extraction sockets
Jung-Bo Huh, Hyo-Jung Lee, Ui-Woo Jung
Abstract
Purpose: This randomized clinical trial was conducted to assess the safety and effectiveness of ErhBMP-2 in alveolar bone regeneration, as well as in preserving β-TCP/HA bone graft material containing ErhBMP-2. Materials and Methods: This study involved 72 patients from three study centers. The patients were divided into two groups: an experimental group that received ErhBMP-2-coated β-TCP/HA and a control group that received β-TCP/HA graft material alone. The graft materials were transplanted immediately after tooth extraction. CT scans were taken before transplantation and 3 months after surgery, and healing status was compared between the two groups. The efficacy endpoints used to evaluate the degree of bone induction included alveolar bone height and three measurements of bone width. A paired t-test was used to determine the significance of the changes (p < 0.05). Results: Changes in alveolar bone height were -1.087 ± 1.413 mm in the control group and -0.059 ± 0.960 mm in the experimental group (p < 0.01). At 25% extraction socket length (ESL), the changes in bone width were 0.006 ± 1.149 mm in the control group and 1.279 ± 1.387 mm in the experimental group. At 50% ESL, the changes were 0.542 ± 1.157 mm and 1.239 ± 1.249 mm, respectively. The differences were statistically significant at 25% ESL (p < 0.01) and 50% ESL (p < 0.05). No adverse reactions to the graft material were observed during the study. Conclusion: ErhBMP-2-coated β-TCP/HA was found to be more effective in preserving alveolar bone than conventional β-TCP/HA alloplastic bone graft material.
Multicenter, randomized clinical trial on the efficacy and safety of Escherichia coli-derived rhBMP-2 with β-TCP and hydroxyapatite in human extraction sockets
Jung-Bo Huh, Hyo-Jung Lee, Ui-Won Jung
Abstract
Purpose: This randomized clinical trial was conducted to assess the safety and effectiveness of ErhBMP-2 in alveolar bone regeneration, as well as in the preservation of β-TCP/HA bone graft material containing ErhBMP-2. Materials and Methods: This study involved 72 patients from three study centers. The patients were divided into two groups: an experimental group that received ErhBMP-2-coated β-TCP/HA and a control group that received β-TCP/HA graft material alone. The graft materials were transplanted immediately after tooth extraction. CT scans were taken before transplantation and 3 months after surgery, and healing status was compared between the two groups. The efficacy endpoints used to evaluate the degree of bone induction included alveolar bone height and three measurements of bone width. A paired t-test was used to determine the significance of the changes (p < 0.05). Results: Changes in alveolar bone height were -1.087 ± 1.413 mm in the control group and -0.059 ± 0.960 mm in the experimental group (p < 0.01). At 25% extraction socket length (ESL), the changes in bone width were 0.006 ± 1.149 mm in the control group and 1.279 ± 1.387 mm in the experimental group. At 50% ESL, the changes were 0.542 ± 1.157 mm and 1.239 ± 1.249 mm, respectively. The differences were statistically significant at 25% ESL (p < 0.01) and 50% ESL (p < 0.05). No adverse reactions to the graft material were observed during the study. Conclusion: ErhBMP-2-coated β-TCP/HA was found to be more effective in preserving alveolar bone than conventional β-TCP/HA alloplastic bone graft material.
Induction of bone formation by Escherichia coli-expressed recombinant human BMP-2 using block-type macroporous biphasic calcium phosphate in orthotopic and ectopic rat models
J-C. Park
Abstract
Background and Objective: The potential of Escherichia coli-expressed recombinant human bone morphogenetic protein-2 (ErhBMP-2) to support new bone formation and maturation using a block-type macroporous biphasic calcium phosphate (bMBCP) carrier was evaluated in orthotopic and ectopic rat models. Materials and Methods: Critical-size calvarial defects, 8 mm in diameter, and subcutaneous pockets were created in 32 Sprague-Dawley rats. Each site received either rhBMP-2 at a dose of 2.5 µg in a bMBCP carrier or bMBCP alone as the control. Implant sites were evaluated using histological and histometric analyses after 2- and 8-week healing intervals, with eight animals per group at each interval. Results: ErhBMP-2/bMBCP supported significantly greater bone formation in calvarial defects at both 2 and 8 weeks, with 10.8% and 25.4% bone formation, respectively, compared with 5.3% and 14.0% in the control group (p < 0.01). In the ectopic sites, bone formation was observed only in the ErhBMP-2/bMBCP group and was significantly greater at 8 weeks (7.5%) than at 2 weeks (4.5%) (p < 0.01). Appositional and endochondral bone formation was usually associated with a significant increase in fatty marrow at 8 weeks. The bMBCP carrier showed no evidence of bioresorption. Conclusion: ErhBMP-2/bMBCP induced significant bone formation in both calvarial and ectopic sites.
Effects of Anodized Implants Coated With Escherichia coli-Derived Recombinant Human Bone Morphogenetic Protein-2 on Osseointegration in Rabbits
Jung-Bo Huh, Jae-Jun Ryu, Jong-Eun Kim, Do-Wan Kim, Sun-Jong Kim, Young-Bum Park, Young-Su Kim, Su-Young Lee, Jeong-Yeol Lee, Sang-Wan Shin
Abstract
The aim of the present study was to evaluate the effects of anodized implants coated with Escherichia coli-derived recombinant human bone morphogenetic protein-2 (ErhBMP-2) on osseointegration using stability tests and histometric analysis. Nine adult New Zealand White rabbits, weighing 4.5–5 kg, were used in the study. Thirty-six implants, 5.0 mm in length and 4.0 mm in diameter, were divided into two groups: anodized implants, used as the control group, and ErhBMP-2-coated anodized implants, used as the experimental group. The ErhBMP-2 coating was applied at a concentration of 1.5 mg/mL, with 18 µg per implant (Cowellmedi Co., Busan, Korea). In each rabbit, four implants were placed bilaterally in the tibiae. The control and experimental implants were randomly placed in either the left or right tibia. The rabbits were sacrificed at the end of each healing period, at 2, 4, and 12 weeks after surgery. Implant stability was evaluated by resonance frequency analysis. For histometric evaluation, bone-to-implant contact (BIC) and intra-thread bone density (ITBD) were measured using a light microscope. The implant stability quotient (ISQ) value was significantly greater in the experimental group than in the control group at 12 weeks (p < 0.05). ITBD increased over time in the experimental group (p < 0.05). Post hoc comparison analysis showed a statistically significant interaction between time-dependent ITBD change and ErhBMP-2 application, particularly between 2 and 4 weeks (p = 0.033). In this study, a greater degree of osseointegration was observed in the experimental group. ErhBMP-2-coated anodized implants may be particularly useful in cases with poor bone quality or insufficient bone volume.
The Effects of rhBMP-2 Injection at Distraction Osteogenesis of Rats’ Tibia
Hae-Ryong Song, Sung-Eun Kim, Hyo-Geun Kim
Abstract
Distraction osteogenesis is a widely used bone-lengthening procedure. However, delayed bone consolidation after distraction osteogenesis can lead to complications related to external fixators and refractures after removal of the external frame. We hypothesized that local administration of recombinant human bone morphogenetic protein-2 (rhBMP-2) alone could accelerate long-bone healing. Eighteen Sprague-Dawley rats underwent 5 mm lengthening by distraction osteogenesis and were then divided into two groups. The control group received no injection, whereas the experimental group received a local injection of 0.5 mL of rhBMP-2 at a concentration of 0.05 mg/mL. Six samples were evaluated at each time point, 2, 4, and 8 weeks, using plain radiographs, micro-computed tomography, and histological staining. On plain radiographs, the percentage pixel count for bone consolidation was higher in the experimental group at 2, 4, and 8 weeks, and was significantly higher than that in the control group at 8 weeks (p < 0.05). Micro-CT evaluation showed that bone volume percentage and trabecular thickness were higher in the experimental group than in the control group. Histological examination showed neovascularization and new stromal cells in the control group at 2 weeks, whereas intramembranous ossification was observed in the experimental group at 2 weeks. At 4 weeks, both intramembranous and endochondral ossification were observed in the experimental group but not in the control group. At 8 weeks, trabecular thickness was greater in the experimental group than in the control group. These findings suggest that local injection of rhBMP-2 at the distraction site can accelerate bone healing during distraction osteogenesis.
Effects of Anodized Implants Coated With Escherichia coli-Derived Recombinant Human Bone Morphogenetic Protein-2 on Osseointegration in Rabbits
Jung-Bo Huh, Jae-Jun Ryu, Jong-Eun Kim
Abstract
The aim of the present study was to evaluate the effects of anodized implants coated with Escherichia coli-derived recombinant human bone morphogenetic protein-2 (ErhBMP-2) on osseointegration using stability tests and histometric analysis. Nine adult New Zealand White rabbits, weighing 4.5–5 kg, were used in the study. Thirty-six implants, 5.0 mm in length and 4.0 mm in diameter, were divided into two groups: anodized implants, used as the control group, and ErhBMP-2-coated anodized implants, used as the experimental group. The ErhBMP-2 coating was applied at a concentration of 1.5 mg/mL, with 18 µg per implant (Cowellmedi Co., Busan, Korea). In each rabbit, four implants were placed bilaterally in the tibiae. The control and experimental implants were randomly placed in either the left or right tibia. The rabbits were sacrificed at the end of each healing period, at 2, 4, and 12 weeks after surgery. Implant stability was evaluated by resonance frequency analysis. For histometric evaluation, bone-to-implant contact (BIC) and intra-thread bone density (ITBD) were measured using a light microscope. The implant stability quotient (ISQ) value was significantly greater in the experimental group than in the control group at 12 weeks (p < 0.05). ITBD increased over time in the experimental group (p < 0.05). Post hoc comparison analysis showed a statistically significant interaction between time-dependent ITBD change and ErhBMP-2 application, particularly between 2 and 4 weeks (p = 0.033). In this study, a greater degree of osseointegration was observed in the experimental group. ErhBMP-2-coated anodized implants may be particularly useful in cases with poor bone quality or insufficient bone volume.
High tibial osteotomy using polycaprolactone-tricalcium phosphate polymer wedge in a micro pig model
H.-C. Lim, J.-H. Bae
Abstract
Medial open-wedge high tibial osteotomy has gained popularity in recent years, but adequate supporting material is required in the osteotomy gap to allow early weight-bearing and rapid union. The purpose of this study was to investigate whether implantation of a polycaprolactone-tricalcium phosphate composite scaffold wedge could enhance osteotomy healing in a micropig model. Open-wedge high tibial osteotomies were performed in 12 micropigs aged 12 to 16 months. A scaffold wedge was inserted into six osteotomy sites, while the other six sites were left open. Bone healing was evaluated at 3 and 6 months using plain radiographs, CT scans, bone mineral density measurements, and histological examination. Complete bone union was obtained at 6 months in both groups. No collapse at the osteotomy site, loss of correction, or fixation failure was observed in either group. Hematoxylin and eosin staining demonstrated infiltration of new bone tissue into the macropores and along the periphery of the implanted scaffold in the scaffold group. CT scans and bone mineral density measurements showed that, at 6 months, specimens in the scaffold group had higher bone mineral density than those in the control group. However, implantation of the polycaprolactone-tricalcium phosphate composite scaffold wedge did not enhance osteotomy healing.
Alveolar ridge augmentation using anodized implants coated with Escherichia coli–derived recombinant human bone morphogenetic protein 2
Jung-Bo Huh, Chan-Kyung Park, Se-Eun Kim, Kyung-Mi Shim, Kyung-Hee Choi, Sun-Jong Kim, June-Sung Shim, Sang-Wan Shin
Abstract
Objective The aim of this study was to examine the effect of Escherichia coli–derived recombinant human bone morphogenetic protein 2 (ErhBMP-2) coated onto anodized implant to stimulate local bone formation, including osseointegration and the vertical augmentation of the alveolar ridge. Study design Six young male adult beagle dogs were used. A crestal area was leveled on both sides of each test subject by removing minimal cortical bone using a round bur and without exposing cancellous bone. After a 2-month healing period, 3 anodized implants (length 8 mm, diameter 4 mm; Cowellmedi, Busan, Korea) were placed 5 mm into the mandibular alveolar ridge in either side. Each animal received 6 implants that were either coated with ErhBMP-2 (0.75 or 1.5 mg/mL concentration; Cowellmedi) or uncoated. This was performed using a randomized split-mouth design. A total of 36 implants were used for this study. Twelve noncoated implants were used as control, and 24 BMP-coated implants were used as our experimental group, which was further divided into 2 groups of 12 implants each with different BMP concentration of 0.75 and 1.5 mg/mL. Radiologic examinations were performed immediately after implant placement and 4 and 8 weeks after implant placement. The amount of bone augmentation was evaluated by measuring the distance from the uppermost point of the cover screw to the marginal bone. Implant stability quotient (ISQ) values were measured immediately after surgery and 8 weeks after implant placement. Statistical analysis was performed using one-way analysis of variance (SPSS version 17.0) and multiple-comparison tests. Statistical significance was established at the 95% confidence level. Results Implants coated with ErhBMP-2 at 0.75 mg/mL (BMP 0.75 group) and 1.5 mg/mL (BMP 1.5 group) exhibited significant vertical bone formation compared with the control group (mean ± SD): 0.88 ± 0.94 versus 0.60 ± 0.64 versus −0.52 ± 0.64 mm, respectively; P < .05. There was a significant difference between the 3 groups in bone level change (P < .05). The BMP 0.75 and BMP 1.5 groups exhibited significant changes in ISQ compared with the control group: 8.17 ± 8.31 versus 11.50 ± 9.02 versus 2.17 ± 7.61, respectively; P < .05. Conclusion Within the limits of this study, the ErhBMP-2 coating on an anodized implant may stimulate vertical bone augmentation, which significantly increases implant stability on completely healed alveolar ridges.
Recombinant human bone morphogenetic protein-2 and pancreatic cancer: a retrospective cohort study
Daniel Mines, Yun Gu, Tzuyung Doung Kou
Abstract
Purpose: To assess whether the use of recombinant human bone morphogenetic protein-2 (rhBMP-2) during lumbar spinal fusion surgery affects the subsequent risk of pancreatic cancer. Methods: Using US Medicare claims data, we performed a retrospective cohort study of patients who underwent lumbar spinal fusion surgery between October 2003 and December 2005. The study population, all aged over 66 years, was identified using procedure codes for lumbar fusion. Claims for bone morphogenetic protein (BMP) were used as a proxy for rhBMP-2 exposure, although another BMP product shared the same code. Pancreatic cancer was identified from claims indicating this diagnosis and cancer-specific therapy. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results: Of the 93,654 patients included in the study, the mean age was 75 years, and 16.5% had claims for BMP. During a mean follow-up period of 1.4 years, 91 patients were diagnosed with pancreatic cancer: eight in the BMP cohort and 83 in the non-BMP cohort. Consistent with previous research, pancreatic cancer was associated with older age, male sex, Black race, and diabetes mellitus. Compared with patients who did not receive BMP, those exposed to BMP were not at increased risk of pancreatic cancer, with an adjusted HR of 0.70 and a 95% CI of 0.34–1.45. A chart review substudy validated the exposure measure, showing that 52 of 55 patients with claims for BMP had received rhBMP-2. Conclusions: In this large study of elderly patients who underwent lumbar fusion surgery, exposure to BMP was not associated with an increased risk of pancreatic cancer.
The induction of bone formation in rat calvarial defects and subcutaneous tissues by recombinant human BMP-2 produced in Escherichia coli
Ji-Hyun Lee, Chang-Sung Kim, Kyung-Hee Choi
Abstract
We investigated the ability of recombinant human bone morphogenetic protein-2 produced from Escherichia coli (ErhBMP-2) to induce orthotopic and ectopic bone formation in rat models. BMP-2 was expressed in E. coli and extracted from inclusion bodies. Critical-size calvarial defects and subcutaneous pouches were created in rats, and absorbable collagen sponges (ACSs) were loaded with different doses of ErhBMP-2 for implantation. ACS alone and sham surgery controls were also included. Implant sites were evaluated using histological and/or histometric analyses after 2- or 8-week healing intervals. In the calvarial defect model, enhanced bone formation was observed with all doses of ErhBMP-2, whereas only limited amounts of new bone were found in the controls. In the ectopic subcutaneous implant model, bone formation was clearly observed in all animals treated with ErhBMP-2 at 2 weeks. However, less new bone formation was detected at 8 weeks than at 2 weeks. Nevertheless, the remaining new bone at 8 weeks showed a more advanced degree of remodeling and maturation than that observed at 2 weeks. These results indicate that ErhBMP-2 is osteoinductive under controlled in vivo conditions.
Effects of Polycaprolactone-Tricalcium Phosphate, Recombinant Human Bone Morphogenetic Protein-2 and Dog Mesenchymal Stem Cells on Bone Formation: Pilot Study in Dogs
Sun-Jong Kim, Myung-Rae Kim, Jin-Sub Oh
Abstract
Purpose: The aim of this study was to evaluate the survival, proliferation, and bone-forming potential of dog mesenchymal stem cells (dMSCs) in graft materials composed of polycaprolactone-tricalcium phosphate (PCL-TCP), autologous fibrin glue (AFG), recombinant human bone morphogenetic protein-2 (rhBMP-2), and dMSCs after transplantation to the scapulae of adult beagle dogs. Materials and Methods: Two beagle dogs were used in this study. The total dose of rhBMP-2 applied to each block was 10 µg at a concentration of 50 µg/mg. Cortical bone of the dog scapula was removed to match the size of the PCL-TCP block (5.0 × 5.0 × 8.0 mm), and the graft material was fixed with an orthodontic mini-implant. Four experimental groups were prepared: Group 1, PCL-TCP + AFG; Group 2, PCL-TCP + AFG + dMSCs; Group 3, PCL-TCP + AFG + dMSCs + rhBMP-2; and Group 4, PCL-TCP + AFG + dMSCs + rhBMP-2 + PCL membrane. The survival and proliferation of dMSCs were evaluated using fluorescence microscopy and histological staining at 2 and 4 weeks after transplantation. Results: Survival and proliferation of dMSCs were confirmed, and histological observation showed that the injected cells proliferated well within the scaffolds. Bone formation was more pronounced in the rhBMP-2 groups, Groups 3 and 4, than in the non-BMP groups, Groups 1 and 2. Conclusion: Bone ingrowth occurred in the PCL-TCP scaffold when combined with rhBMP-2, whereas MSCs alone did not significantly affect bone formation.
Effects of rhBMP-2 Coating Tricalcium Phosphate on Socket Preservation in Dog Extraction Socket
Sun-Jong Kim, Jong-Jin Kwon, Dong-yul Lee
Abstract
Recently, research on bone morphogenetic protein (BMP) has continued to advance because of its potential as a substitute for bone grafting. The purpose of the present study was to evaluate the efficacy of BMP-2 for bone regeneration during socket healing after tooth extraction through volumetric analysis of extraction sockets using cone beam computed tomography (CBCT). In six dogs, the bilateral third and fourth mandibular premolars were hemisected, and the distal roots were removed. The distal extraction sockets on the left side were filled with BMP-2-coated TCP, whereas the contralateral premolar sockets were left without bone grafting. Three dogs were sacrificed after 4 weeks of healing, and the other three dogs were sacrificed after 12 weeks. The extraction sockets were then scanned using CBCT, and the data were reconstructed into consecutive 1 mm-thick two-dimensional slices. The total volume of the delineated socket was calculated. The results were statistically analyzed using ANOVA and a multiple comparison test. There were no differences in socket width between the two groups after 4 and 12 weeks of healing. However, BMP-2-coated TCP was effective in preserving the vertical bone dimension of the extraction socket after 4 weeks of healing (p < 0.05). Within the limitations of this study, BMP-2-coated TCP may preserve socket height during the early healing stage in the dog mandible.