Alveolar ridge augmentation with rhBMP-2 and bone-to-implant contact in induced bone.

The objective of this study was to examine alveolar ridge augmentation following implantation of recombinant human bone morphogenetic protein (rhBMP-2) with an allogeneic freeze-dried demineralized bone matrix (DBM) mixed with autologous blood. A second objective was to evaluate bone-to-implant contact in induced bone. Bilateral surgically created supraalveolar ridge defects in five young adult beagle dogs were implanted with the rhBMP-2-DBM-blood device. Transmucosal dental implants were placed at weeks 8 and 16 postsurgery The animals were euthanized 24 weeks following ridge augmentation. Healing was uneventful in all animals. Radiographic observations indicated substantial bone formation, including regions of radiolucency, at week 8. At week 16, the radiolucencies were generally resolved, and the trabecular structure of the induced bone resembled that of the adjacent residual bone. There were no remarkable differences in radiographic observations between weeks 16 and 24 after ridge augmentation. Histologic analysis revealed dense woven and lamellar induced bone. Any residual DBM appeared remineralized, at least in part. A large portion of the dental implants (approximately 70%) were housed in induced bone with evidence of limited crestal resorption. There was no significant difference in bone density between induced and residual bone, and the levels of bone-to-implant contact were similar (approximately 55%). The rhBMP-2 construct used in this study has a potential to augment alveolar ridge defects. Also, no difference in levels of osseointegration may be expected in induced and residual bone following a two-stage procedure of rhBMP-2-induced ridge augmentation and dental implant placement.

Cigarette smoking negatively affects healing response following flap debridement surgery.

BACKGROUND: The purpose of the present parallel design, controlled clinical trial was to evaluate the treatment outcome following flap debridement surgery (FDS) in cigarette smokers compared to non-smokers. METHODS: After initial therapy, 57 systemically healthy subjects with moderate to advanced periodontitis who presented with one area (at least 3 teeth) where surgery was required were selected. Twenty-eight patients (mean age: 39.6 years, 20 males) were smokers (> or = 10 cigarettes/day); 29 patients (mean age: 43.9 years, 7 males) were non-smokers. Full-mouth plaque (FMP) and bleeding on probing (BOP) scores, probing depth (PD), clinical attachment level (CAL), and recession depth (RD) were assessed immediately before and 6 months following surgery. Only sites with presurgery PD > or = 4 mm were used for statistical analysis. RESULTS: Presurgery FMP and BOP were similar in smokers and non-smokers and significantly decreased postsurgery in both groups. Overall, PD reduction and CAL gain were greater, although not significantly, in non-smokers (2.4 +/- 0.9 mm and 1.6 +/- 0.7 mm, respectively) than in smokers (1.9 +/- 0.7 mm and 1.2 +/- 0.7 mm, respectively). For moderate sites (PD 4 to 6 mm), no significant differences in PD and CAL changes were found between groups. For deep sites (PD > or = 7 mm), PD reduction was 3.0 +/- 1.0 mm in smokers and 4.0 +/- 0.8 mm in non-smokers, and CAL gain amounted to 1.8 +/- 1.1 mm in smokers and 2.8 +/- 1.0 mm in non-smokers (P = 0.0477). In smokers, 16% of deep sites healed to postsurgery PD values < or = 3 mm as compared to 47% in non-smokers (P = 0.0000); 58% of deep sites in smokers showed a CAL gain > or = 2 mm, as compared to 82% in non-smokers (P = 0.0000). CONCLUSIONS: Results of the study indicated that: 1) FDS determined a statistically significant PD reduction and CAL gain in patients with moderate to advanced periodontitis; 2) smokers exhibited a trend towards less favorable healing response following FDS compared to non-smokers, both in terms of PD reduction and CAL gain; and 3) this trend reached clinical and statistical significance at sites with initial deep PD.

Periodontal repair in dogs: effect of transforming growth factor-beta 1 on alveolar bone and cementum regeneration.

BACKGROUND: Transforming growth factor-beta (TGF-beta) represents a family of growth-modulating proteins with fundamental roles in connective tissue and bone development. The objective of this study was to evaluate the potential for regeneration of alveolar bone and cementum following surgical implantation of recombinant human TGF-beta 1 (rhTGF-beta 1). METHOD: Bilateral, critical size, supra-alveolar periodontal defects in 5 beagle dogs were surgically implanted with rhTGF-beta 1 in a calcium carbonate carrier (CaCO3) or with carrier alone. The animals were euthanized at 4 weeks postsurgery and block-biopsies of the defects were processed for histologic and histometric analysis. RESULTS: Surgical implantation of rhTGF-beta 1 resulted in minimal, if any, stimulation of alveolar bone or cementum regeneration. Linear bone and cementum regeneration in rhTGF-beta 1-treated defects was 1.2+/-0.6 and 0.01+0.01 mm, respectively. Corresponding values for the controls were 1.0+/-0.6 and 0.01+/-0.03 mm. CONCLUSIONS: The results suggest that, under the conditions (dose, carrier, defect type) evaluated here, treatment of periodontal defects in beagle dogs with rhTGF-beta 1 may be of limited clinical benefit.

Periodontal repair in dogs: effect of recombinant human transforming growth factor-beta1 on guided tissue regeneration.

This study evaluated alveolar bone and cementum regeneration following surgical implantation of recombinant human transforming growth factor-beta1 (rhTGF-beta1) in conjunction with guided tissue regeneration (GTR). Supraalveolar, critical size, periodontal defects were surgically created around the 3rd and 4th mandibular premolar teeth in right and left jaw quadrants in 5 beagle dogs. Alternate jaw quadrants in consecutive animals received rhTGF-beta1, in a CaCO3/hydroxyethyl starch carrier with GTR, or carrier with GTR alone (control). 20 microg of rhTGF-beta1 in buffer solution was incorporated into approximately 0.8 ml of carrier for each defect scheduled to receive rhTGF-beta1. Animals were sacrificed at week 4 postsurgery and tissue blocks were harvested and processed for histometric analysis. Clinical healing was generally uneventful. Minor membrane exposures were observed. Defects with membrane exposure displayed an inflammatory infiltrate underneath the membrane. Bone regeneration of trabecular nature, apparent in all animals, was generally limited to the very apical aspect of the defects. Cementum regeneration was limited without obvious differences between experimental conditions. Comparing rhTGF-beta1, to control defects, statistically significant differences were found for area (1.8+/-0.4 and 1.3+/-0.6 mm2, respectively; p<0.05) and density (0.3+/-0.1 and 0.2+/-0.03, respectively; p<0.05) of alveolar bone regeneration. Observed differences are small and represent a clinically insignificant potential for enhanced regeneration in this preclinical model. Within the limitations of study, it may be concluded that rhTGF-beta1 has a restricted potential to enhance alveolar bone regeneration in conjunction with GTR.

Effect of allogeneic, freeze-dried, demineralized bone matrix on guided bone regeneration in supra-alveolar peri-implant defects in dogs.

This randomized, split-mouth design study evaluated the adjunctive effect of allogeneic, freeze-dried, demineralized bone matrix on guided bone regeneration in a critical-size, supra-alveolar, peri-implant defect model. Contralateral supra-alveolar peri-implant defects, 5 mm in height, each including two titanium implants, were surgically created in five beagle dogs. Demineralized bone matrix in autologous blood was placed over the implants in one randomly selected mandibular jaw quadrant. A space-making expanded-polytetrafluoroethylene membrane was used to provide guided bone regeneration bilaterally. Following a 16-week healing interval, tissue blocks were harvested and prepared for histometric analysis. Differences between experimental conditions (guided bone regeneration sites with and without demineralized bone) were evaluated using paired t tests (n = 4). Demineralized bone particles were discernible, with limited signs of resorption. The bone matrix particles appeared to be solidified within a dense connective tissue matrix and in close contact with the implants. Limited matrix remineralization was apparent adjacent to the alveolar crest. No statistically significant differences were found between experimental conditions for any parameter examined. Peri-implant defect height averaged 5.0 +/- 0.2 mm and 4.9 +/- 0.4 mm, vertical bone regeneration 1.5 +/- 0.9 mm and 1.1 +/- 0.4 mm, osseointegration within the extent of the defect 10.0 +/- 3.9% and 15.3 +/- 5.3%, osseointegration within the extent of regenerated bone 30.4 +/- 13.7% and 52.1 +/- 17.9%, and osseointegration within the alveolar base 68.8 +/- 13.1% and 74.4 +/- 7.1% for guided bone sites with and without demineralized bone, respectively (P > .05). The results suggest that freeze-dried demineralized bone has no adjunctive effect on guided bone regeneration in supra-alveolar peri-implant defects, that guided bone regeneration has a limited potential to enhance alveolar regeneration in this defect model, and that a 16-week healing interval appears insufficient for turnover and maturation of demineralized bone under provisions for guided bone regeneration.

Bone morphogenetic protein-2 for peri-implant bone regeneration and osseointegration.

Recombinant human bone morphogenetic protein-2 (rhBMP-2) induced bone regeneration and osseointegration was evaluated in supraalveolar peri-implant defects in 5 beagle dogs. Alveolar bone was reduced 5 mm in height in mandibular premolar areas and the premolars were extracted. Three 10 mm titanium fixtures were placed 5 mm into each reduced alveolar crest, leaving 5 mm in a supraalveolar position. Alternate quadrants in consecutive animals received a surgical implant consisting of 2 ml rhBMP-2 (0.43 mg/ml) in a type I bovine collagen carrier, or the carrier alone (control). Fixtures and surgical implants were submerged under the gingival flaps. The healing interval was 16 weeks. Histometric and radiographic evaluations were made. Defect height averaged (+/- SD) 5.3 +/- 0.2 and 5.1 +/- 0.2 mm for rhBMP-2 and control defects, respectively (P > 0.05, n = 5, paired, t-test) Bone regeneration (height) averaged 4.2 +/- 1.0 and 0.5 +/- 0.3 mm for rhBMP-2 and control defects, respectively (P < 0.05). Bone regeneration (area) averaged 6.1 +/- 6.3 and 0.2 +/- 0.2 mm2 for rhBMP-2 and control defects, respectively (P > 0.05). Osseointegration within the confines of the defect averaged 19.1 +/- 10.1% and 8.2 +/- 4.6% for rhBMP-2 and control defects, respectively (P > 0.05). Osseointegration within regenerated bone averaged 29.1 +/- 9.8% and 65.3 +/- 15.3% for rhBMP-2 and control defects, respectively (P < 0.05). Osseointegration within the retained alveolar bone averaged 67.1 +/- 4.6% and 68.1 +/- 3.6% for rhBMP-2 and control defects, respectively (P > 0.05). The results suggest that there is a potential for rhBMP-2 induced bone regeneration and osseointegration in surgical peri-implant defects.

Periodontal healing following reconstructive surgery: effect of guided tissue regeneration.

Clinical healing following guided tissue regeneration (GTR) in deep intrabony pockets was compared to healing following gingival flap surgery alone (GFS). 15 patients received the GTR treatment including an expanded polytetrafluoroethylene membrane. 13 other patients received the control treatment GFS. A postsurgery protocol emphasizing wound stability and infection control was used. Treatment effects were evaluated 6 months postsurgery. Mean pre-surgery probing depth for the GTR and control treatments was 7.5 +/- 1.0 and 7.7 +/- 1.5 mm, respectively. Significant probing depth reduction (3.8 +/- 1.2 and 2.9 +/- 1.1 mm), attachment level improvement (2.4 +/- 2.1 and 2.2 +/- 1.2 mm) and bone fill (2.0 +/- 2.0 and 2.4 +/- 0.9 mm) followed the GTR and control protocols, respectively (p < 0.01). Significant differences between GTR and control treatments were observed in probing depth reduction (p < 0.01) and in gingival recession increase (1.7 +/- 1.5 and 0.7 +/- 0.9 mm, respectively; p < 0.05). The results suggest that GTR procedures compared to GFS have similar clinical potential in intrabony pockets, under the present protocol.

Periodontal repair in dogs: evaluation of rhBMP-2 carriers.

This study evaluated candidate carriers for recombinant human bone morphogenetic protein-2 (rhBMP-2)-driven periodontal regeneration. Previous experiments indicated the ability of rhBMP-2 in a particulate delivery system to result in substantial regeneration of bone and periodontal regeneration. In the present study, canine demineralized bone matrix (DBM), bovine deorganified crystalline bone matrix (Bio-Oss), an absorbable collagen sponge (ACS) of type I bovine collagen, poly(D,L-lactide-co-glycolide) microparticles (PLGA), and polylactic acid granules (Drilac) were tested for their ability to support rhBMP-2 (0.2 mg/mL implant volume)-driven periodontal regeneration. The implants were tested in routine critical size canine supra-alveolar periodontal defects with transgingival tooth positioning. Contralateral defects in six beagle dogs were semirandomly assigned to receive: DBM/rhBMP-2, DBM (no rhBMP-2), Bio-Oss/rhBMP-2, ACS/rhBMP-2, PLGA/rhBMP-2, or Drilac/rhBMP-2. Animals were sacrificed 8 weeks postsurgery, and block sections of the defects were processed for light microscopy. Substantial bone regeneration was observed in all defects implanted with rhBMP-2. Other measures of periodontal healing, including cementum regeneration and presence of ankylosis, were more variable between the implants. DBM and Bio-Oss performed well as carriers for rhBMP-2-driven periodontal regeneration, although other impediments to their clinical use exist. This study indicates that qualities of the carrier system, including its space-maintaining capacity can affect the ability of rhBMP-2 to regenerate both alveolar bone and periodontal attachment.

Does root surface conditioning with citric acid delay healing?

Effects of topical citric acid application on tissue maturation was studied in standardized periodontal defects in 6 beagle dogs. Following elevation of facial mucoperiosteal flaps, fenestration defects, 3 mm in diameter, were made through the cortical bone and recessed 0.5 mm into the dentin of maxillary canines. 1 defect in each dog was conditioned with a saturated solution of citric acid for 3 min and then rinsed with saline. Control defects in contralateral teeth were treated with saline only for the same length of time. The defects were covered with an expanded polytetrafluoroethylene membrane and the flaps repositioned and sutured. 14 days postsurgery, healing appeared more advanced along the defect walls and floor than in the center of the defect in all instances. Histometrically, citric acid-conditioned defects exhibited a higher density of collagen fibers along the defect walls and floor and adjacent to the barrier membrane as well as more advanced resolution of the residual blood clot than the surgical controls. Differences in fibroblast density within specimen pairs were non-significant. All control defects but none of the acid-conditioned defects showed an artifactual split between the dentin walls and the granulation tissue. This study failed to support the contention that topical application of citric acid to root surfaces may delay healing following periodontal surgery.

Intra - and inter-examiner reproducibility in constant force probing.

This study evaluated intra- and inter-examiner reproducibility for a conventional manual probe versus a computer-interfaced force-controlled periodontal probe. 2 examiners recorded probing depths (PD) and relative attachment levels (AL) at 1128 sites in 15 periodontal maintenance patients. Each site was evaluated 2x, 7 to 10 days apart by both examiners. Probing force for the electronic probe was 15 g. PD intra-examiner reproducibility (within +/- 1.0 mm) for shallow sites (PD < or = 3 mm) was 98.6% versus 91.5% for the conventional versus the electronic probe for examiner 1 and 98.5% versus 88.7% for examiner 2. Corresponding values for deeper sites (PD > 3 mm) were 96.4% versus 85.9% for examiner 1 and 95.1% versus 77.0% for examiner 2. Generally, AL intra-examiner reproducibility was 1 to 3% lower than for PD. PD inter-examiner reproducibility (within +/- 1.0 mm) was 99.2% versus 90.7% for the conventional versus the electronic probe, respectively, for shallow sites and 95.4% versus 76.9% for deeper sites. AL inter-examiner reproducibility (within +/- 1.0 mm) was 1 to 5% lower than for PD. Both intra- and inter-examiner reproducibility was higher for anterior than for posterior sites. Mean PD and AL were similar for both examiners. However, the electronic probe consistently recorded 0.1 to 0.2 mm higher values than the conventional probe. Standard deviations indicated a greater variability for electronic than for manual probing. The results suggest that intra- and inter-examiner reproducibility may not necessarily be higher with an electronic, force-controlled periodontal probe than with a conventional manual probe.

Dynamics of wound healing in periodontal regenerative therapy.

Experimental animal and clinical studies have increased understanding of the biology of healing following periodontal regenerative therapy and factors that may influence the outcome. Formation of a new connective tissue attachment rather than a long junctional epithelium at the tooth-gingival flap interface is dependent upon the completion of a series of interactions among the root surface, plasma and tissue factors, and the connective tissue of the gingival flap. First, plasma proteins must adsorb to and remain in undisturbed contact with a generally noncompromised root surface. Next, adhesion of the established fibrin clot to the root surface must remain intact. Within days, a cellular and fibrous attachment will form; however, the tooth-gingival flap interface will still be vulnerable to wound-rupturing forces. Within two weeks the interface may have gained sufficient mechanical strength to offset such forces, at least in limited periodontal defects. Eventually, maturation of the fibrous attachment, including bone and cementum formation, will occur, particularly following adequate space provision by barrier membranes (guided tissue regeneration). A novel research focus involves how advances in molecular biology can translate to periodontal regenerative therapy. Bone morphogenetic proteins (BMPs) have been shown to support healing in a variety of skeletal sites. Recent research has demonstrated clinically significant alveolar bone and cementum regeneration with the use of a recombinant human BMP-2 implant. Such data suggest that growth-promoting substances, such as rhBMP-2, may significantly enhance periodontal regeneration and that use of such substances may radically recast current periodontal regenerative therapy.

"Collagen adhesion" revisited.

Histologic studies of periodontal reconstructive therapies have repeatedly shown a zone of nondescript connective tissue adaptation, or collagen adhesion, to the root surface between the apical extension of the junctional epithelium and the coronal extension of identifiable regenerated cementum. To clarify the nature of this zone, supra-alveolar periodontal defects were created bilaterally in the mandibular premolar region in three beagle dogs, and exposed roots were instrumented to remove the cementum. Flaps were then coronally advanced and sutured. Histologic analysis after 12 weeks of healing showed instrumented root dentin not associated with junctional epithelium, new cementum, root resorption, or ankylosis in 27 of 60 root surfaces. In 10 of these specimens subsequently examined by transmission electron microscopy, collagen fibrils were generally oriented parallel to and in close proximity to the root. A mechanism of collagen attachment was, in fact, functioning at sites of collagen adhesion; these areas may validly be included in the histologic attachment level reported in studies of periodontal reconstructive therapy.

Periodontal regenerative potential of space-providing expanded polytetrafluoroethylene membranes and recombinant human bone morphogenetic proteins.

A concept of space provision to support skeletal repair has long been used in orthopedic and oral maxillofacial reconstructive therapy. More recently, this concept has been studied and adapted to periodontal reconstructive therapy. Other studies have demonstrated that skeletal tissues represent a significant reservoir of growth factors, including bone morphogenetic proteins. Such factors have been shown to stimulate skeletal repair in preclinical models and in clinical defects. We herein review studies using the critical size supraalveolar periodontal defect model in which clinically meaningful periodontal regeneration was achieved following reconstructive surgery, including space provision by reinforced expanded polytetrafluoroethylene membranes or including surgical implantation of recombinant human bone morphogenetic protein-2. Potential mechanisms involved in observed regeneration are discussed.

Periodontal repair in dogs: recombinant human bone morphogenetic protein-2 significantly enhances periodontal regeneration.

This study evaluated bone and cementum regeneration following periodontal reconstructive surgery using recombinant human bone morphogenetic protein-2 (rhBMP-2) in six beagle dogs. Surgically created mandibular supraalveolar premolar tooth defects in contralateral jaw quadrants were randomly assigned to receive rhBMP-2 or control vehicle. Clinical defect height was prepared to 5 mm. rhBMP-2 was applied with synthetic bioerodable particles and autologous blood using 20 micrograms rhBMP-2 per 100 microliters implant volume. Flaps were advanced to submerge the teeth and sutured. The dogs were sacrificed 8 weeks postsurgery. Histometric recordings included defect height, height and area of alveolar bone regeneration, height of cementum regeneration, root resorption, and ankylosis. Group means, standard deviations, and P values are shown (Student t test; n = 6). Histometric defect height for rhBMP-2 and control defects was 3.7 +/- 0.3 and 3.9 +/- 0.4 mm, respectively (P = 0.446). Height of alveolar bone regeneration amounted to 3.5 +/- 0.6 and 0.8 +/- 0.6 mm for rhBMP-2 and control defects, respectively (P = 0.000). Corresponding values for bone area were 8.4 +/- 4.5 and 0.4 +/- 0.5 mm2, respectively (P = 0.006). Cementum regeneration was observed in all experimental defects (17/17) and in 15 out of 17 controls, averaging 1.6 +/- 0.6 and 0.4 +/- 0.3 mm for rhBMP-2 and control defects, respectively (P = 0.005). Small amounts of root resorption were seen in rhBMP-2 defects, whereas controls exhibited substantial resorption (0.2 +/- 0.1 and 1.1 +/- 0.3 mm, respectively; P = 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Reproducibility of periodontal probing using a conventional manual and an automated force-controlled electronic probe.

A total of 1,128 sites in 15 periodontal maintenance patients were examined twice, 7 to 10 days apart, to evaluate reproducibility of periodontal probing by a conventional manual and an automated force-controlled electronic probe. Probing depths (PD) and relative attachment levels (AL) were recorded to the nearest 0.5 mm with both instruments. At each visit, all sites were probed first with the conventional and then with the electronic probe. Reproducibility of PD at shallow sites (PD < or = 3 mm) by the manual probe was 59.1% for exact agreement and 98.6% within +/- 1.0 mm variation. For the electronic probe, corresponding values were 41.3% and 91.5%, respectively. Reproducibility of PD measurements at deeper sites (PD > 3 mm), was 33.0% for exact match and 96.4% within +/- 1.0 mm for the manual and, correspondingly, 31.7% and 85.9% for the electronic probe. Reproducibility of AL followed a similar pattern, but was consistently lower than for PD. Reproducibility was consistently higher for anterior than for posterior sites and, for some comparisons, higher in the maxilla than in the mandible. These differences were smaller for the manual than for the electronic probe. Time required to complete the probing was longer for the conventional probe than for the electronic instrument. Under the prevailing study conditions, the automated force-controlled electronic probe failed to offer significant advantages over the conventional manual probe.

Evaluating surgical, non-surgical therapy in periodontic patients.

Eleven highly susceptible periodontitis patients volunteered for a one-year prospective study of surgical and non-surgical periodontal therapy. The patients had high oral hygiene standards and had not received antimicrobial therapy within six months. This study suggests that both types of therapy are equally effective in treating recurrent lesions.

Periodontal repair in dogs: space provision by reinforced ePTFE membranes enhances bone and cementum regeneration in large supraalveolar defects.

Regeneration of alveolar bone and cementum following reconstructive therapy with reinforced space providing expanded polytetrafluorethylene (ePTFE) membranes was evaluated in supraalveolar mandibular premolar periodontal defects in five beagle dogs. The surgically-created defects in contralateral jaw quadrants were randomly assigned to receive the dome-shaped membrane or serve as surgical control. Flaps were positioned to completely submerge the teeth and sutured. The dogs were sacrificed 8 weeks after surgery and tissue blocks including teeth and surrounding structures processed for histology. Membrane treated defects in two animals became exposed and infected leaving intact quadrants in three dogs for histometric analysis. Parameters evaluated included defect height, height and area of regenerated alveolar bone, height of regenerated cementum, root resorption, and ankylosis. Mean defect height approximated 4.1 mm. Mean height (+/- s.d.) of regenerated alveolar bone amounted to 2.9 +/- 0.6 and 0.6 +/- 0.2 mm for membrane and control defects, respectively (P = 0.006). Corresponding values for bone area were 1.4 +/- 0.7 and 0.4 +/- 0.4 mm2 (P = 0.02). Cementum regeneration was observed in all teeth averaging (+/- s.d.) 1.6 +/- 0.3 mm for membrane treated and 0.1 +/- 0.1 mm for control defects (P = 0.01). Small amounts of root resorption were seen in all teeth with no significant difference between treatments. Ankylosis was noticed in three membrane treated and two control teeth. The present study provides a biologic rationale for space provision for enhanced bone and cementum regeneration in periodontal defects subject to reconstructive therapy.