Jaebum Lee - Academia.edu (original) (raw)

Papers by Jaebum Lee

Research paper thumbnail of Investigation of Bone Regeneration Efficacy of New Bovine Bone Minerals in a Canine Mandibular Critical Defect Model

www.advhealthmat.de, 2023

This article is protected by copyright. All rights reserved. 2 This study aimed to investigate th... more This article is protected by copyright. All rights reserved. 2 This study aimed to investigate the bone regeneration effect of bovine hydroxyapatite-processed biomaterials Bone-XB and S1-XB in a beagle mandibular defect model. A total of four saddle-type critical sizes (15 mm × 10 mm) bone defects were created in each dog: two defects in the left mandible and two defects in the right mandible. The defect control (DC) group was kept unfilled, and the other three defects were filled with three different biomaterials as follows: positive control Bio-Oss ® (Bio-Oss group), Bone-XB (XB group), and S1-XB (S1-XB group). Bone regeneration was evaluated by radiography, micro-computed tomography, and histological analysis. we revealed that Bone-XB and S1-XB significantly increased newly formed bone, defect filling percentage, and bone healing score compared to the DC group, which was confirmed by bone microstructure augmentation (bone volume/total volume, trabecular number, and trabecular thickness). Interestingly, no significant differences were observed between the Bone-XB, S1-XB, and Bio-Oss groups. We suggest that Bone-XB or S1-XB stimulates bone regeneration demonstrated by the increase in newly formed bone and bone microstructure, thereby improving bone defect filling, which was equivalent to the Bio-Oss ®. Therefore, bovine hydroxyapatite-processed Bone-XB or S1-XB could be considered effective biomaterials for correcting critical-size bone defects or fractures.

Research paper thumbnail of Screening of Hydroxyapatite Biomaterials for Alveolar Augmentation Using a Rat Calvaria Critical-Size Defect Model: Bone Formation/Maturation and Biomaterials Resolution

Biomolecules

Background: Natural (bovine-/equine-/porcine-derived) or synthetic hydroxyapatite (HA) biomateria... more Background: Natural (bovine-/equine-/porcine-derived) or synthetic hydroxyapatite (HA) biomaterials appear to be the preferred technologies among clinicians for bone augmentation procedures in preparation for implant dentistry. The aim of this study was to screen candidate HA biomaterials intended for alveolar ridge augmentation relative to their potential to support local bone formation/maturation and to assess biomaterial resorption using a routine critical-size rat calvaria defect model. Methods: Eighty adult male Sprague Dawley outbred rats obtained from a approved-breeder, randomized into groups of ten, were used. The calvaria defects (ø8 mm) either received sham surgery (empty control), Bio-Oss (bovine HA/reference control), or candidate biomaterials including bovine HA (Cerabone, DirectOss, 403Z013), and bovine (403Z014) or synthetic HA/ß-TCP (Reprobone, Ceraball) constructs. An 8 wk healing interval was used to capture the biomaterials’ resolution. Results: All biomaterials ...

Research paper thumbnail of Periodontal regeneration: focus on growth and differentiation factors

Dental clinics of North America, 2010

Several growth and differentiation factors have shown potential as therapeutic agents to support ... more Several growth and differentiation factors have shown potential as therapeutic agents to support periodontal wound healing/regeneration, although optimal dosage, release kinetics, and suitable delivery systems are still unknown. Experimental variables, including delivery systems, dose, and the common use of poorly characterized preclinical models, make it difficult to discern the genuine efficacy of each of these factors. Only a few growth and differentiation factors have reached clinical evaluation. It appears that well-defined discriminating preclinical models followed by well-designed clinical trials are needed to further investigate the true potential of these and other candidate factors. Thus, current research is focused on finding relevant growth and differentiation factors, optimal dosages, and the best approaches for delivery to develop clinically meaningful therapies in patient-centered settings.

Research paper thumbnail of The critical-size supraalveolar peri-implant defect model: reproducibility in histometric data acquisition of alveolar bone formation and osseointegration

Journal of Clinical Periodontology, 2009

Research paper thumbnail of Crestal remodelling and osseointegration at surface-modified commercially pure titanium and titanium alloy implants in a canine model

Journal of Clinical Periodontology, 2012

Ti-6Al-7Nb alloys exhibit enhanced mechanical properties and corrosion resistance and may represe... more Ti-6Al-7Nb alloys exhibit enhanced mechanical properties and corrosion resistance and may represent an improvement to present commercially pure (CP) titanium oral implant technology. To evaluate crestal remodelling and osseointegration at CP titanium compared with Ti-6Al-7Nb alloy oral implants using a canine model. Two threaded anodized CP titanium and two Ti-6Al-7Nb alloy anodized oral implants (ø4.5 × 6.1 mm) were placed into each jaw quadrant in the edentulated posterior mandible in six adult male Hound Labrador mongrel dogs. Abutments were placed onto the implants, and the mucogingival flaps were adapted and sutured for transmucosal wound healing. Block biopsies were collected for histometric analysis following an 8-week healing interval. Healing was uneventful. Bone density outside and within the root of the threads averaged (± SE) 49.0 ± 4.5% and 38.7 ± 5.1% for CP titanium implants and 43.2 ± 3.6% and 34.2 ± 4.8% for Ti-6Al-7Nb alloy implants. Mean osseointegration reached 68.0 ± 4.4% and 62.8 ± 2.5% for CP titanium and Ti-6Al-7Nb alloy implants, respectively. Although crestal resorption at lingual sites averaged 0.2 ± 0.1 mm for both technologies, crestal resorption at buccal sites averaged 0.9 ± 0.2 and 1.0 ± 0.6 mm for CP titanium and Ti-6Al-7Nb alloy implants, respectively. There were no statistically significant differences between implant technologies for any parameter assessed. Notably, advanced/advancing buccal crestal resorption exposing the implant threads was observed in 50% of the implants (four of six animals) regardless of implant technology; osteoclastic resorption still observed at 8 weeks following implant placement. Within the limitations of study, anodized Ti-6Al-7Nb alloy implants may represent a feasible alternative to benchmark anodized CP titanium implants. Remodelling of the buccal crestal plate resulting in advanced bone loss appears a major impediment to oral implant osseointegration and possibly, in extension, implant maintenance.

Research paper thumbnail of First-Order Mathematical Correlation Between Damping and Resonance Frequency Evaluating the Bone-Implant Interface

The International journal of oral & maxillofacial implants

Various advanced technologies have been designed to estimate dental implant stability, including ... more Various advanced technologies have been designed to estimate dental implant stability, including insertion torque, implant damping using the Periotest, and resonance frequency analysis expressed in implant stability quotient units. This study aimed to establish the relationship between the estimates for these three techniques. Bovine cortical bone blocks were trimmed to square shapes of precisely controlled thickness and density. Thereafter, 4-mm-diameter × 10-mm-long implants were placed in the bone blocks using 30-, 45-, and 60-Ncm insertion torques. Implant damping and resonance frequency analysis were conducted at four angles for each implant. Spearman correlation coefficients were calculated to examine the relationship between insertion torque, resonance frequency analysis, and implant damping measured values. Resonance frequency analysis and implant damping estimates exhibited a strong inverse correlation (r = -0.98, P < .001). A linear equation was formulated: Periotest va...

Research paper thumbnail of Erbium, chromium:yttrium–scandium–gallium–garnet laser-assisted sinus graft procedure

Lasers in Medical Science, 2009

The possibility of using lasers in the field of dentistry has been a subject of investigation. Th... more The possibility of using lasers in the field of dentistry has been a subject of investigation. There are few reports that any laser systems have been used for bony window osteotomy by direct sinus grafting. In this study, erbium, chromium:yttrium-scandium-gallium-garnet (Er, Cr:YSGG) laser of various laser systems was used for 12 sinus bone grafts in ten patients, and the efficiency of the laser was evaluated according to the osteotomy time and the rate of sinus membrane perforation in the clinical results; the mechanism is described. Eight of the 12 procedures were performed by direct sinus grafting with the Er,Cr: YSGG laser without membrane perforation (perforation ratio 33.3%). Operating time for bony window osteotomy with laser alone was 2-7 minutes [3 min 24 s on average; 3.4±1.4 min (mean ± standard deviation)], and all the implants placed immediately were successful.

Research paper thumbnail of Evaluation of a novel calcium phosphate-coated titanium porous oxide implant surface: a study in rabbits

PURPOSE To evaluate osseointegration of a novel calcium phosphate (CaP)-coated titanium porous ox... more PURPOSE To evaluate osseointegration of a novel calcium phosphate (CaP)-coated titanium porous oxide implant surface. MATERIALS AND METHODS Twenty adult male New Zealand White rabbits were used. Each animal received two titanium porous oxide-surfaced implants (benchmark control: TiUnite, Nobel Biocare) and two novel CaP-coated titanium porous oxide-surfaces implants; they were randomly allocated to contralateral tibia implant sites. The animals were sacrificed after 2 or 4 weeks, and tissues were evaluated histometrically. RESULTS Healing was generally uneventful. A removal torque analysis showed significantly higher mean (± SE) peak values for the control implants than for the test implants at 2 weeks (31.4 ± 2.5 Ncm versus 20.4 ± 1.8 Ncm) and 4 weeks (48.4 ± 5.5 Ncm versus 30.3 ± 3.9 Ncm). Light microscopy showed no significant differences in local bone density around control and test implants at 2 and 4 weeks (range, 85% to 91% within the thread area and 91% to 95% immediately ou...

Research paper thumbnail of Screening of candidate biomaterials for alveolar augmentation using a critical-size rat calvaria defect model

Journal of clinical periodontology, 2018

To screen candidate biomaterials intended for alveolar augmentation relative to their potential t... more To screen candidate biomaterials intended for alveolar augmentation relative to their potential to enhance local bone formation using a routine critical-size (ø8-mm) rat calvaria defect model. One hundred and forty male Sprague Dawley outbred rats, age 11-12 weeks, weight 325-375 g, obtained from USDA approved breeder, randomised into 14 groups of 10 animals, each received one of the following treatments: sham-surgery (empty control), Bio-Oss (bovine HA/reference control), or candidate biomaterials including bovine HA, synthetic HA/ß-TCP and calcium phosphate constructs, mineralised/demineralised human bone preparations, a ß-TCP/calcium sulphate and an HA/calcium sulphate putty. A 4-week healing interval was chosen to discern local bone formation using incandescent and polarised light microscopy. Statistical analysis used one-way ANOVA followed by Bonferroni for pairwise comparisons. Candidate biomaterials all displayed biocompatibility. They exhibited limited, if any, appreciable b...

Research paper thumbnail of Sinus Augmentation Using a Mini-pig Model: Effect of Ceramic and Allogeneic Bone Biomaterials

Journal of clinical periodontology, Jan 23, 2017

Present clinical practice broadly relies on off-the-shelf allogeneic, xenogeneic or synthetic bon... more Present clinical practice broadly relies on off-the-shelf allogeneic, xenogeneic or synthetic bone biomaterials in support of sinus augmentation. Also, recombinant human bone morphogenetic protein-2 in an absorbable collagen sponge carrier (rhBMP-2/ACS) has been shown to support clinically relevant bone formation when used to augment the maxillary sinus. To evaluate local bone formation/dental implant osseointegration following implantation of two particulate bone biomaterials using the mini-pig sinus augmentation model. Nine adult Göttingen mini-pigs were used for evaluation of a biphasic ceramic (15%/85% HA/ß-TCP) and an allogeneic mineralized bone biomaterial. Treatments randomized to contralateral sinus sites included sham-surgery (control) and biomaterials. Two threaded dental implants (ø4.0x11.5 mm) were placed at each sinus site. The animals were euthanized at 8 wks for histologic analysis. Execution of the surgical protocol and healing were unremarkable. Limited infraorbital...

Research paper thumbnail of Assessment of Osseointegration Using BSEM versus LM Image Acquisition

Background: Light microscopy (LM) has been routine in the evaluation of dental implant osseointeg... more Background: Light microscopy (LM) has been routine in the evaluation of dental implant osseointegration. Backscatter scanning electron microscopy (BSEM), a technology based on compositional contrast, may provide more distinct evaluation of bone-implant contact (BIC) and peri-implant bone density (BD). Objectives: To compare BSEM and LM in the assessment of dental implant osseointegration in cortical and trabecular bone using a rabbit model. Methods: Central sections from 30 rabbit femoral trabecular and 48 tibial cortical bone implant sites were used. BSEM digital images were obtained using the SEM backscatter detector at 20 kV and a 9-mm working distance. The sections were then stained with hematoxylin/eosin and digital images obtained using a microscope digital camera system. Evaluations of BSEM and LM images were performed by one calibrated, masked examiner; using an image analysis software custom macro; recording BIC, BD outside the threads (BDot) and BD within the threads (BDwt...

Research paper thumbnail of Alveolar Augmentation: Focus on Growth Factors (BMPs)

Mechanical Engineering Series, 2014

ABSTRACT

Research paper thumbnail of Wound healing following surgical and regenerative periodontal therapy

Periodontology 2000, 2015

Research paper thumbnail of Evaluation of a novel calcium phosphate-coated titanium porous oxide implant surface: a study in rabbits

The International journal of oral & maxillofacial implants

To evaluate osseointegration of a novel calcium phosphate (CaP)-coated titanium porous oxide impl... more To evaluate osseointegration of a novel calcium phosphate (CaP)-coated titanium porous oxide implant surface. Twenty adult male New Zealand White rabbits were used. Each animal received two titanium porous oxide-surfaced implants (benchmark control: TiUnite, Nobel Biocare) and two novel CaP-coated titanium porous oxide-surfaces implants; they were randomly allocated to contralateral tibia implant sites. The animals were sacrificed after 2 or 4 weeks, and tissues were evaluated histometrically. Healing was generally uneventful. A removal torque analysis showed significantly higher mean (± SE) peak values for the control implants than for the test implants at 2 weeks (31.4 ± 2.5 Ncm versus 20.4 ± 1.8 Ncm) and 4 weeks (48.4 ± 5.5 Ncm versus 30.3 ± 3.9 Ncm). Light microscopy showed no significant differences in local bone density around control and test implants at 2 and 4 weeks (range, 85% to 91% within the thread area and 91% to 95% immediately outside the threads). At 2 weeks, bone-i...

Research paper thumbnail of Effect of Platform Shift/Switch on Crestal Bone Levels and Mucosal Profile Following Flapless Surgery and Crestal/Subcrestal Implant Placement

Clinical implant dentistry and related research, Jan 29, 2014

Crestal remodeling/bone loss appears a common sequel to dental implant placement. Several hypothe... more Crestal remodeling/bone loss appears a common sequel to dental implant placement. Several hypotheses and clinical strategies have been advanced to explain and avert crestal remodeling; however, causative mechanisms remain unclear and the efficacy of clinical protocol uncertain. The objective of the present study was to provide a histologic record of crestal versus subcrestal implant placement on crestal remodeling and mucosal profile comparing platform shift/switch and standard abutments following flapless implant surgery using a dog model. Four dental implants each were placed into the left and right edentulated posterior mandibles in five adult male hound-Labrador mongrel dogs using a flapless approach including crestal versus subcrestal placement and using platform shift versus standard abutments. Block biopsies were collected for histological/histometric analysis following an 8-week healing interval. Both crestal and subcrestal implant installation resulted in significant cresta...

Research paper thumbnail of Low-Dose Bone Morphogenetic Protein-2/Stromal Cell-Derived Factor-1β Cotherapy Induces Bone Regeneration in Critical-Size Rat Calvarial Defects

Tissue Engineering Part A, 2014

Increasing evidence suggests that stromal cell-derived factor-1 (SDF-1/CXCL12) is involved in bon... more Increasing evidence suggests that stromal cell-derived factor-1 (SDF-1/CXCL12) is involved in bone formation, though underlying molecular mechanisms remain to be fully elucidated. Also, contributions of SDF-1β, the second most abundant splice variant, as an osteogenic mediator remain obscure. We have shown that SDF-1β enhances osteogenesis by regulating bone morphogenetic protein-2 (BMP-2) signaling in vitro. Here we investigate the dose-dependent contribution of SDF-1β to suboptimal BMP-2-induced local bone formation; that is, a dose that alone would be too low to significantly induce bone formation. We utilized a critical-size rat calvarial defect model and tested the hypotheses that SDF-1β potentiates BMP-2 osteoinduction and that blocking SDF-1 signaling reduces the osteogenic potential of BMP-2 in vivo. In preliminary studies, radiographic analysis at 4 weeks postsurgery revealed a dose-dependent relationship in BMP-2-induced new bone formation. We then found that codelivery of SDF-1β potentiates suboptimal BMP-2 (0.5 μg) osteoinduction in a dose-dependent order, reaching comparable levels to the optimal BMP-2 dose (5.0 μg) without apparent adverse effects. Blocking the CXC chemokine receptor 4 (CXCR4)/SDF-1 signaling axis using AMD3100 attenuated the osteoinductive potential of the optimal BMP-2 dose, confirmed by qualitative histologic analysis. In conclusion, SDF-1β provides potent synergistic effects that support BMP-induced local bone formation and thus appears a suitable candidate for optimization of bone augmentation using significantly lower amounts of BMP-2 in spine, orthopedic, and craniofacial settings.

Research paper thumbnail of Evaluation of Implants Coated With Recombinant Human Bone Morphogenetic Protein-2 and Vacuum-Dried Using the Critical-Size Supraalveolar Peri-Implant Defect Model in Dogs

Journal of Periodontology, 2010

Research paper thumbnail of Comparative Study of Chinese Hamster Ovary Cell Versus Escherichia coli- Derived Bone Morphogenetic Protein-2 Using the Critical-Size Supraalveolar Peri-Implant Defect Model

Journal of Periodontology, 2013

Chinese hamster ovary (CHO) cell-derived recombinant human bone morphogenetic protein-2 (rhBMP-2)... more Chinese hamster ovary (CHO) cell-derived recombinant human bone morphogenetic protein-2 (rhBMP-2) has been introduced for spine, long bone, and craniofacial indications. Escherichia coli- (E. coli) derived rhBMP-2 displays comparable efficacy to CHO cell-derived rhBMP-2 in vitro and in small-animal models. The objective of this study is to evaluate the efficacy of E. coli-derived rhBMP-2 compared to the benchmark CHO cell-derived rhBMP-2 using an established large-animal model. Contralateral, critical-size supraalveolar peri-implant defects in six adult male Hound Labrador mongrel dogs received CHO cell- or E. coli-derived rhBMP-2 (0.2 mg/mL) in an absorbable collagen sponge (ACS) carrier. In each quadrant, three dental implants were placed. A titanium mesh device was used to support space provision. The animals received fluorescent bone markers for qualitative evaluations. Animals were euthanized at 8 weeks for histopathologic and histometric evaluation. Clinical healing included significant swelling, but none of the animals experienced wound dehiscences. CHO cell- and E. coli-derived rhBMP-2 supported comparable bone formation (new bone area, 35.8 ± 3.6 versus 30.1 ± 2.2 mm(2); bone density, 31.8% ± 1.6% versus 35.6% ± 2.5%; and osseointegration, 32.9% ± 7.4% versus 33.7% ± 8.1%) without statistically significant differences between treatments. Newly formed immature delicate trabecular bone in fibrovascular marrow filled the space underneath the titanium mesh and extended coronally above the mesh. Seroma formation was frequently observed. There were no discernable qualitative histologic differences between treatments. CHO cell- and E. coli-derived rhBMP-2 in an ACS carrier appear equally effective at inducing local bone formation in support of dental implant osseointegration.

Research paper thumbnail of Effect of rhBMP-2 Dose on Bone Formation/Maturation in a Rat Critical-size Calvarial Defect Model

Journal of Clinical Periodontology, 2014

Background: Application of recombinant human bone morphogenetic protein-2 (rhBMP-2) has been asso... more Background: Application of recombinant human bone morphogenetic protein-2 (rhBMP-2) has been associated with significant adverse events in craniofacial settings, including swelling and seroma formation. Recent work has demonstrated an inverse relationship between bone formation/maturation and rhBMP-2 dose, frequency/severity of adverse events increasing with rising dose. Objective: The objective of this study was to determine the most effective dose for rhBMP-2 soak-loaded onto an absorbable collagen sponge (ACS) carrier for bone formation/maturation using an established defect model. Methods: One hundred sixty-eight outbred male Sprague-Dawley rats, age 11-13 weeks, weight 325-375 g randomized into seven groups of 24 subdivided into groups of eight, were used to provide radiographic and light microscopy observations of bone formation/maturation and aberrant healing events at 2, 4 and 8 weeks following application of rhBMP-2/ACS into critical-size, ø8-mm, through-through, calvarial osteotomy defects for a dose of 1.25, 2.5, 5.0, 10.0 and 20.0 lg rhBMP-2/defect, or serve as ACS or sham-surgery controls. Results: rhBMP-2 dosages ≥2.5 lg/defect showed histological defect closure >90% within 2 weeks, and complete resolution within 4 weeks. Adverse healing events including swelling, excessive bone formation or seroma formation could not be determined with certainty in this defect model. Notably ACS control sites showed complete defect closure at the 8-week healing interval. Conclusions: rhBMP-2/ACS accelerates local bone formation in the rat criticalsize through-through calvarial defect model once reaching an osteoinductive dose threshold. This threshold may already be reached at a 1.25-/2.5-lg dose in this model. No further enhancement to bone formation/maturation may be observed adding rhBMP-2 above the 2.5-lg dose. The 1.25-20.0 lg dose range did not invoke appreciable aberrant healing events.

Research paper thumbnail of Evaluation of implants coated with rhBMP-2 using two different coating strategies: a critical-size supraalveolar peri-implant defect study in dogs

Journal of Clinical Periodontology, 2010

Research paper thumbnail of Investigation of Bone Regeneration Efficacy of New Bovine Bone Minerals in a Canine Mandibular Critical Defect Model

www.advhealthmat.de, 2023

This article is protected by copyright. All rights reserved. 2 This study aimed to investigate th... more This article is protected by copyright. All rights reserved. 2 This study aimed to investigate the bone regeneration effect of bovine hydroxyapatite-processed biomaterials Bone-XB and S1-XB in a beagle mandibular defect model. A total of four saddle-type critical sizes (15 mm × 10 mm) bone defects were created in each dog: two defects in the left mandible and two defects in the right mandible. The defect control (DC) group was kept unfilled, and the other three defects were filled with three different biomaterials as follows: positive control Bio-Oss ® (Bio-Oss group), Bone-XB (XB group), and S1-XB (S1-XB group). Bone regeneration was evaluated by radiography, micro-computed tomography, and histological analysis. we revealed that Bone-XB and S1-XB significantly increased newly formed bone, defect filling percentage, and bone healing score compared to the DC group, which was confirmed by bone microstructure augmentation (bone volume/total volume, trabecular number, and trabecular thickness). Interestingly, no significant differences were observed between the Bone-XB, S1-XB, and Bio-Oss groups. We suggest that Bone-XB or S1-XB stimulates bone regeneration demonstrated by the increase in newly formed bone and bone microstructure, thereby improving bone defect filling, which was equivalent to the Bio-Oss ®. Therefore, bovine hydroxyapatite-processed Bone-XB or S1-XB could be considered effective biomaterials for correcting critical-size bone defects or fractures.

Research paper thumbnail of Screening of Hydroxyapatite Biomaterials for Alveolar Augmentation Using a Rat Calvaria Critical-Size Defect Model: Bone Formation/Maturation and Biomaterials Resolution

Biomolecules

Background: Natural (bovine-/equine-/porcine-derived) or synthetic hydroxyapatite (HA) biomateria... more Background: Natural (bovine-/equine-/porcine-derived) or synthetic hydroxyapatite (HA) biomaterials appear to be the preferred technologies among clinicians for bone augmentation procedures in preparation for implant dentistry. The aim of this study was to screen candidate HA biomaterials intended for alveolar ridge augmentation relative to their potential to support local bone formation/maturation and to assess biomaterial resorption using a routine critical-size rat calvaria defect model. Methods: Eighty adult male Sprague Dawley outbred rats obtained from a approved-breeder, randomized into groups of ten, were used. The calvaria defects (ø8 mm) either received sham surgery (empty control), Bio-Oss (bovine HA/reference control), or candidate biomaterials including bovine HA (Cerabone, DirectOss, 403Z013), and bovine (403Z014) or synthetic HA/ß-TCP (Reprobone, Ceraball) constructs. An 8 wk healing interval was used to capture the biomaterials’ resolution. Results: All biomaterials ...

Research paper thumbnail of Periodontal regeneration: focus on growth and differentiation factors

Dental clinics of North America, 2010

Several growth and differentiation factors have shown potential as therapeutic agents to support ... more Several growth and differentiation factors have shown potential as therapeutic agents to support periodontal wound healing/regeneration, although optimal dosage, release kinetics, and suitable delivery systems are still unknown. Experimental variables, including delivery systems, dose, and the common use of poorly characterized preclinical models, make it difficult to discern the genuine efficacy of each of these factors. Only a few growth and differentiation factors have reached clinical evaluation. It appears that well-defined discriminating preclinical models followed by well-designed clinical trials are needed to further investigate the true potential of these and other candidate factors. Thus, current research is focused on finding relevant growth and differentiation factors, optimal dosages, and the best approaches for delivery to develop clinically meaningful therapies in patient-centered settings.

Research paper thumbnail of The critical-size supraalveolar peri-implant defect model: reproducibility in histometric data acquisition of alveolar bone formation and osseointegration

Journal of Clinical Periodontology, 2009

Research paper thumbnail of Crestal remodelling and osseointegration at surface-modified commercially pure titanium and titanium alloy implants in a canine model

Journal of Clinical Periodontology, 2012

Ti-6Al-7Nb alloys exhibit enhanced mechanical properties and corrosion resistance and may represe... more Ti-6Al-7Nb alloys exhibit enhanced mechanical properties and corrosion resistance and may represent an improvement to present commercially pure (CP) titanium oral implant technology. To evaluate crestal remodelling and osseointegration at CP titanium compared with Ti-6Al-7Nb alloy oral implants using a canine model. Two threaded anodized CP titanium and two Ti-6Al-7Nb alloy anodized oral implants (ø4.5 × 6.1 mm) were placed into each jaw quadrant in the edentulated posterior mandible in six adult male Hound Labrador mongrel dogs. Abutments were placed onto the implants, and the mucogingival flaps were adapted and sutured for transmucosal wound healing. Block biopsies were collected for histometric analysis following an 8-week healing interval. Healing was uneventful. Bone density outside and within the root of the threads averaged (± SE) 49.0 ± 4.5% and 38.7 ± 5.1% for CP titanium implants and 43.2 ± 3.6% and 34.2 ± 4.8% for Ti-6Al-7Nb alloy implants. Mean osseointegration reached 68.0 ± 4.4% and 62.8 ± 2.5% for CP titanium and Ti-6Al-7Nb alloy implants, respectively. Although crestal resorption at lingual sites averaged 0.2 ± 0.1 mm for both technologies, crestal resorption at buccal sites averaged 0.9 ± 0.2 and 1.0 ± 0.6 mm for CP titanium and Ti-6Al-7Nb alloy implants, respectively. There were no statistically significant differences between implant technologies for any parameter assessed. Notably, advanced/advancing buccal crestal resorption exposing the implant threads was observed in 50% of the implants (four of six animals) regardless of implant technology; osteoclastic resorption still observed at 8 weeks following implant placement. Within the limitations of study, anodized Ti-6Al-7Nb alloy implants may represent a feasible alternative to benchmark anodized CP titanium implants. Remodelling of the buccal crestal plate resulting in advanced bone loss appears a major impediment to oral implant osseointegration and possibly, in extension, implant maintenance.

Research paper thumbnail of First-Order Mathematical Correlation Between Damping and Resonance Frequency Evaluating the Bone-Implant Interface

The International journal of oral & maxillofacial implants

Various advanced technologies have been designed to estimate dental implant stability, including ... more Various advanced technologies have been designed to estimate dental implant stability, including insertion torque, implant damping using the Periotest, and resonance frequency analysis expressed in implant stability quotient units. This study aimed to establish the relationship between the estimates for these three techniques. Bovine cortical bone blocks were trimmed to square shapes of precisely controlled thickness and density. Thereafter, 4-mm-diameter × 10-mm-long implants were placed in the bone blocks using 30-, 45-, and 60-Ncm insertion torques. Implant damping and resonance frequency analysis were conducted at four angles for each implant. Spearman correlation coefficients were calculated to examine the relationship between insertion torque, resonance frequency analysis, and implant damping measured values. Resonance frequency analysis and implant damping estimates exhibited a strong inverse correlation (r = -0.98, P < .001). A linear equation was formulated: Periotest va...

Research paper thumbnail of Erbium, chromium:yttrium–scandium–gallium–garnet laser-assisted sinus graft procedure

Lasers in Medical Science, 2009

The possibility of using lasers in the field of dentistry has been a subject of investigation. Th... more The possibility of using lasers in the field of dentistry has been a subject of investigation. There are few reports that any laser systems have been used for bony window osteotomy by direct sinus grafting. In this study, erbium, chromium:yttrium-scandium-gallium-garnet (Er, Cr:YSGG) laser of various laser systems was used for 12 sinus bone grafts in ten patients, and the efficiency of the laser was evaluated according to the osteotomy time and the rate of sinus membrane perforation in the clinical results; the mechanism is described. Eight of the 12 procedures were performed by direct sinus grafting with the Er,Cr: YSGG laser without membrane perforation (perforation ratio 33.3%). Operating time for bony window osteotomy with laser alone was 2-7 minutes [3 min 24 s on average; 3.4±1.4 min (mean ± standard deviation)], and all the implants placed immediately were successful.

Research paper thumbnail of Evaluation of a novel calcium phosphate-coated titanium porous oxide implant surface: a study in rabbits

PURPOSE To evaluate osseointegration of a novel calcium phosphate (CaP)-coated titanium porous ox... more PURPOSE To evaluate osseointegration of a novel calcium phosphate (CaP)-coated titanium porous oxide implant surface. MATERIALS AND METHODS Twenty adult male New Zealand White rabbits were used. Each animal received two titanium porous oxide-surfaced implants (benchmark control: TiUnite, Nobel Biocare) and two novel CaP-coated titanium porous oxide-surfaces implants; they were randomly allocated to contralateral tibia implant sites. The animals were sacrificed after 2 or 4 weeks, and tissues were evaluated histometrically. RESULTS Healing was generally uneventful. A removal torque analysis showed significantly higher mean (± SE) peak values for the control implants than for the test implants at 2 weeks (31.4 ± 2.5 Ncm versus 20.4 ± 1.8 Ncm) and 4 weeks (48.4 ± 5.5 Ncm versus 30.3 ± 3.9 Ncm). Light microscopy showed no significant differences in local bone density around control and test implants at 2 and 4 weeks (range, 85% to 91% within the thread area and 91% to 95% immediately ou...

Research paper thumbnail of Screening of candidate biomaterials for alveolar augmentation using a critical-size rat calvaria defect model

Journal of clinical periodontology, 2018

To screen candidate biomaterials intended for alveolar augmentation relative to their potential t... more To screen candidate biomaterials intended for alveolar augmentation relative to their potential to enhance local bone formation using a routine critical-size (ø8-mm) rat calvaria defect model. One hundred and forty male Sprague Dawley outbred rats, age 11-12 weeks, weight 325-375 g, obtained from USDA approved breeder, randomised into 14 groups of 10 animals, each received one of the following treatments: sham-surgery (empty control), Bio-Oss (bovine HA/reference control), or candidate biomaterials including bovine HA, synthetic HA/ß-TCP and calcium phosphate constructs, mineralised/demineralised human bone preparations, a ß-TCP/calcium sulphate and an HA/calcium sulphate putty. A 4-week healing interval was chosen to discern local bone formation using incandescent and polarised light microscopy. Statistical analysis used one-way ANOVA followed by Bonferroni for pairwise comparisons. Candidate biomaterials all displayed biocompatibility. They exhibited limited, if any, appreciable b...

Research paper thumbnail of Sinus Augmentation Using a Mini-pig Model: Effect of Ceramic and Allogeneic Bone Biomaterials

Journal of clinical periodontology, Jan 23, 2017

Present clinical practice broadly relies on off-the-shelf allogeneic, xenogeneic or synthetic bon... more Present clinical practice broadly relies on off-the-shelf allogeneic, xenogeneic or synthetic bone biomaterials in support of sinus augmentation. Also, recombinant human bone morphogenetic protein-2 in an absorbable collagen sponge carrier (rhBMP-2/ACS) has been shown to support clinically relevant bone formation when used to augment the maxillary sinus. To evaluate local bone formation/dental implant osseointegration following implantation of two particulate bone biomaterials using the mini-pig sinus augmentation model. Nine adult Göttingen mini-pigs were used for evaluation of a biphasic ceramic (15%/85% HA/ß-TCP) and an allogeneic mineralized bone biomaterial. Treatments randomized to contralateral sinus sites included sham-surgery (control) and biomaterials. Two threaded dental implants (ø4.0x11.5 mm) were placed at each sinus site. The animals were euthanized at 8 wks for histologic analysis. Execution of the surgical protocol and healing were unremarkable. Limited infraorbital...

Research paper thumbnail of Assessment of Osseointegration Using BSEM versus LM Image Acquisition

Background: Light microscopy (LM) has been routine in the evaluation of dental implant osseointeg... more Background: Light microscopy (LM) has been routine in the evaluation of dental implant osseointegration. Backscatter scanning electron microscopy (BSEM), a technology based on compositional contrast, may provide more distinct evaluation of bone-implant contact (BIC) and peri-implant bone density (BD). Objectives: To compare BSEM and LM in the assessment of dental implant osseointegration in cortical and trabecular bone using a rabbit model. Methods: Central sections from 30 rabbit femoral trabecular and 48 tibial cortical bone implant sites were used. BSEM digital images were obtained using the SEM backscatter detector at 20 kV and a 9-mm working distance. The sections were then stained with hematoxylin/eosin and digital images obtained using a microscope digital camera system. Evaluations of BSEM and LM images were performed by one calibrated, masked examiner; using an image analysis software custom macro; recording BIC, BD outside the threads (BDot) and BD within the threads (BDwt...

Research paper thumbnail of Alveolar Augmentation: Focus on Growth Factors (BMPs)

Mechanical Engineering Series, 2014

ABSTRACT

Research paper thumbnail of Wound healing following surgical and regenerative periodontal therapy

Periodontology 2000, 2015

Research paper thumbnail of Evaluation of a novel calcium phosphate-coated titanium porous oxide implant surface: a study in rabbits

The International journal of oral & maxillofacial implants

To evaluate osseointegration of a novel calcium phosphate (CaP)-coated titanium porous oxide impl... more To evaluate osseointegration of a novel calcium phosphate (CaP)-coated titanium porous oxide implant surface. Twenty adult male New Zealand White rabbits were used. Each animal received two titanium porous oxide-surfaced implants (benchmark control: TiUnite, Nobel Biocare) and two novel CaP-coated titanium porous oxide-surfaces implants; they were randomly allocated to contralateral tibia implant sites. The animals were sacrificed after 2 or 4 weeks, and tissues were evaluated histometrically. Healing was generally uneventful. A removal torque analysis showed significantly higher mean (± SE) peak values for the control implants than for the test implants at 2 weeks (31.4 ± 2.5 Ncm versus 20.4 ± 1.8 Ncm) and 4 weeks (48.4 ± 5.5 Ncm versus 30.3 ± 3.9 Ncm). Light microscopy showed no significant differences in local bone density around control and test implants at 2 and 4 weeks (range, 85% to 91% within the thread area and 91% to 95% immediately outside the threads). At 2 weeks, bone-i...

Research paper thumbnail of Effect of Platform Shift/Switch on Crestal Bone Levels and Mucosal Profile Following Flapless Surgery and Crestal/Subcrestal Implant Placement

Clinical implant dentistry and related research, Jan 29, 2014

Crestal remodeling/bone loss appears a common sequel to dental implant placement. Several hypothe... more Crestal remodeling/bone loss appears a common sequel to dental implant placement. Several hypotheses and clinical strategies have been advanced to explain and avert crestal remodeling; however, causative mechanisms remain unclear and the efficacy of clinical protocol uncertain. The objective of the present study was to provide a histologic record of crestal versus subcrestal implant placement on crestal remodeling and mucosal profile comparing platform shift/switch and standard abutments following flapless implant surgery using a dog model. Four dental implants each were placed into the left and right edentulated posterior mandibles in five adult male hound-Labrador mongrel dogs using a flapless approach including crestal versus subcrestal placement and using platform shift versus standard abutments. Block biopsies were collected for histological/histometric analysis following an 8-week healing interval. Both crestal and subcrestal implant installation resulted in significant cresta...

Research paper thumbnail of Low-Dose Bone Morphogenetic Protein-2/Stromal Cell-Derived Factor-1β Cotherapy Induces Bone Regeneration in Critical-Size Rat Calvarial Defects

Tissue Engineering Part A, 2014

Increasing evidence suggests that stromal cell-derived factor-1 (SDF-1/CXCL12) is involved in bon... more Increasing evidence suggests that stromal cell-derived factor-1 (SDF-1/CXCL12) is involved in bone formation, though underlying molecular mechanisms remain to be fully elucidated. Also, contributions of SDF-1β, the second most abundant splice variant, as an osteogenic mediator remain obscure. We have shown that SDF-1β enhances osteogenesis by regulating bone morphogenetic protein-2 (BMP-2) signaling in vitro. Here we investigate the dose-dependent contribution of SDF-1β to suboptimal BMP-2-induced local bone formation; that is, a dose that alone would be too low to significantly induce bone formation. We utilized a critical-size rat calvarial defect model and tested the hypotheses that SDF-1β potentiates BMP-2 osteoinduction and that blocking SDF-1 signaling reduces the osteogenic potential of BMP-2 in vivo. In preliminary studies, radiographic analysis at 4 weeks postsurgery revealed a dose-dependent relationship in BMP-2-induced new bone formation. We then found that codelivery of SDF-1β potentiates suboptimal BMP-2 (0.5 μg) osteoinduction in a dose-dependent order, reaching comparable levels to the optimal BMP-2 dose (5.0 μg) without apparent adverse effects. Blocking the CXC chemokine receptor 4 (CXCR4)/SDF-1 signaling axis using AMD3100 attenuated the osteoinductive potential of the optimal BMP-2 dose, confirmed by qualitative histologic analysis. In conclusion, SDF-1β provides potent synergistic effects that support BMP-induced local bone formation and thus appears a suitable candidate for optimization of bone augmentation using significantly lower amounts of BMP-2 in spine, orthopedic, and craniofacial settings.

Research paper thumbnail of Evaluation of Implants Coated With Recombinant Human Bone Morphogenetic Protein-2 and Vacuum-Dried Using the Critical-Size Supraalveolar Peri-Implant Defect Model in Dogs

Journal of Periodontology, 2010

Research paper thumbnail of Comparative Study of Chinese Hamster Ovary Cell Versus Escherichia coli- Derived Bone Morphogenetic Protein-2 Using the Critical-Size Supraalveolar Peri-Implant Defect Model

Journal of Periodontology, 2013

Chinese hamster ovary (CHO) cell-derived recombinant human bone morphogenetic protein-2 (rhBMP-2)... more Chinese hamster ovary (CHO) cell-derived recombinant human bone morphogenetic protein-2 (rhBMP-2) has been introduced for spine, long bone, and craniofacial indications. Escherichia coli- (E. coli) derived rhBMP-2 displays comparable efficacy to CHO cell-derived rhBMP-2 in vitro and in small-animal models. The objective of this study is to evaluate the efficacy of E. coli-derived rhBMP-2 compared to the benchmark CHO cell-derived rhBMP-2 using an established large-animal model. Contralateral, critical-size supraalveolar peri-implant defects in six adult male Hound Labrador mongrel dogs received CHO cell- or E. coli-derived rhBMP-2 (0.2 mg/mL) in an absorbable collagen sponge (ACS) carrier. In each quadrant, three dental implants were placed. A titanium mesh device was used to support space provision. The animals received fluorescent bone markers for qualitative evaluations. Animals were euthanized at 8 weeks for histopathologic and histometric evaluation. Clinical healing included significant swelling, but none of the animals experienced wound dehiscences. CHO cell- and E. coli-derived rhBMP-2 supported comparable bone formation (new bone area, 35.8 ± 3.6 versus 30.1 ± 2.2 mm(2); bone density, 31.8% ± 1.6% versus 35.6% ± 2.5%; and osseointegration, 32.9% ± 7.4% versus 33.7% ± 8.1%) without statistically significant differences between treatments. Newly formed immature delicate trabecular bone in fibrovascular marrow filled the space underneath the titanium mesh and extended coronally above the mesh. Seroma formation was frequently observed. There were no discernable qualitative histologic differences between treatments. CHO cell- and E. coli-derived rhBMP-2 in an ACS carrier appear equally effective at inducing local bone formation in support of dental implant osseointegration.

Research paper thumbnail of Effect of rhBMP-2 Dose on Bone Formation/Maturation in a Rat Critical-size Calvarial Defect Model

Journal of Clinical Periodontology, 2014

Background: Application of recombinant human bone morphogenetic protein-2 (rhBMP-2) has been asso... more Background: Application of recombinant human bone morphogenetic protein-2 (rhBMP-2) has been associated with significant adverse events in craniofacial settings, including swelling and seroma formation. Recent work has demonstrated an inverse relationship between bone formation/maturation and rhBMP-2 dose, frequency/severity of adverse events increasing with rising dose. Objective: The objective of this study was to determine the most effective dose for rhBMP-2 soak-loaded onto an absorbable collagen sponge (ACS) carrier for bone formation/maturation using an established defect model. Methods: One hundred sixty-eight outbred male Sprague-Dawley rats, age 11-13 weeks, weight 325-375 g randomized into seven groups of 24 subdivided into groups of eight, were used to provide radiographic and light microscopy observations of bone formation/maturation and aberrant healing events at 2, 4 and 8 weeks following application of rhBMP-2/ACS into critical-size, ø8-mm, through-through, calvarial osteotomy defects for a dose of 1.25, 2.5, 5.0, 10.0 and 20.0 lg rhBMP-2/defect, or serve as ACS or sham-surgery controls. Results: rhBMP-2 dosages ≥2.5 lg/defect showed histological defect closure >90% within 2 weeks, and complete resolution within 4 weeks. Adverse healing events including swelling, excessive bone formation or seroma formation could not be determined with certainty in this defect model. Notably ACS control sites showed complete defect closure at the 8-week healing interval. Conclusions: rhBMP-2/ACS accelerates local bone formation in the rat criticalsize through-through calvarial defect model once reaching an osteoinductive dose threshold. This threshold may already be reached at a 1.25-/2.5-lg dose in this model. No further enhancement to bone formation/maturation may be observed adding rhBMP-2 above the 2.5-lg dose. The 1.25-20.0 lg dose range did not invoke appreciable aberrant healing events.

Research paper thumbnail of Evaluation of implants coated with rhBMP-2 using two different coating strategies: a critical-size supraalveolar peri-implant defect study in dogs

Journal of Clinical Periodontology, 2010