Periodontal regeneration with a combination of enamel matrix proteins and autogenous bone grafting.

BACKGROUND: Attempts to stimulate periodontal regeneration in the past have focused on either filling the defect with some type of material or providing a space for host cells to repopulate the site and elicit new tissue. In some cases, these approaches have been combined with the assumption that the filler material will help maintain the space necessary for the host cells to invade the area. Growth stimulating substances such as growth factors and other proteins have also been used to encourage periodontal tissue regeneration and histological evaluation supports the use of these substances. Thus, the role for and the necessity of a certain amount of space maintenance for periodontal regeneration is not exactly understood. In addition, it is not known if there is some critical size required for space maintenance or for exactly how long the space must be maintained in order for the host cells to stimulate new cementum, periodontal ligament, and bone. The goal of this study was to evaluate periodontal regeneration in intrabony defects of various sizes treated with a combination of enamel matrix proteins and autogenous bone graft. METHODS: Periodontal defects ranging in size from 1 to 6 mm were randomized and created bilaterally beside three teeth in the mandibles of baboons. Plaque was allowed to accumulate around wire ligatures placed into the defects. After 2 months, the wire ligatures were removed, the teeth and roots scaled and root planed, and a notch was placed with a chisel at the base of the defect. On one side of the mandible, neutral ethylene diamine tetracetic acid and enamel matrix derivative (EMD) were first used to treat the defect. Autogenous bone taken from the same surgical site was treated with enamel matrix derivative in a dampen dish and then added to the EMD-treated defects. The other side of the mandible served as control with neutral ethylene diamine tetracetic acid and scaling and root planing. Flaps were sutured and the animals were allowed to heal without oral hygiene procedures. After 5 months, the animals were sacrificed and the teeth were processed for histological evaluation. RESULTS: The results revealed new cementum, periodontal ligament with Sharpey's fibers, and new bone tissue similar to native periodontal tissues. Remnants of the autogenous bone chips were still present at this 5-month post-healing period. Thus periodontal regeneration occurred in all sizes of the periodontal defects. In general, EMD plus autogenous graft treatment resulted in greater tissue formation than controls. In fact, in many cases, very dramatic tissue formation occurred far coronal to the base of the defects in the EMD plus autogenous graft-treated lesions. In addition, horizontal bone fill occurred in the defects and was prominent in the 4 or 6 mm wide lesions. When evaluating the combined 1 and 2 mm defects, the height of new cementum with EMD plus graft was 3.88 mm versus 2.03 mm in the controls, a statistically significant (P < 0.005) difference. In the wider (4 and 6 mm) lesions, this difference was not significant and was much less between treated and control lesions with 2.78 and 2.57 mm of new cementum respectively. In the case of new bone height, in the smaller lesions EMD plus graft resulted in 4.00 mm new bone versus 2.22 mm in the controls, again a statistically significant (P < 0.005) difference. In the larger lesions, EMD plus autogenous bone graft had 3.24 mm new bone height compared to 2.71 mm in the controls, a difference that was not statistically significant. Additionally, in the smaller lesions, new cementum width at the level of the notch was twice as great (statistically significant, P < 0.015) in the EMD plus graft sites compared to control. The width of the periodontal ligament at the coronal aspect of the new bone tissue was similar in the smaller lesions between treated and control sites. The results from the wider defects must be interpreted cautiously as the interproximal bone heights were remodeled adjacent to the wider defects and likely limited the potential for regeneration. CONCLUSIONS: The combination of enamel matrix derivative plus autogenous bone graft stimulated statistically significant periodontal regeneration in the more narrow 1 and 2 mm lesions. No statistically significant difference was observed in the wider 4 and 6 mm lesions. In many cases, dramatic amounts of new cementum, Sharpey's fibers, periodontal ligament, and bone tissue were formed far above the notch placed at the base of the contaminated defects. This was especially significant considering the width of some of the defects and the fact that no oral hygiene was performed over the 5-month healing period. This periodontal regeneration occurred in the absence of exogenous growth factors or barrier membranes. In summary, the combination of enamel matrix derivative and autogenous bone represents a therapeutic combination that can be highly effective in stimulating significant amounts of periodontal regeneration.

Influence of the size of the microgap on crestal bone levels in non-submerged dental implants: a radiographic study in the canine mandible.

BACKGROUND: Accumulating evidence suggests that alveolar crestal bone resorption occurs as a result of the microgap that is present between the implant-abutment interface in dental implants. The objective of this longitudinal radiographic study was to determine whether the size of the interface or the microgap between the implant and abutment influences the amount of crestal bone loss in unloaded non-submerged implants. METHODS: Sixty titanium implants having sandblasted with large grit, acid-etched (SLA) endosseous surfaces were placed in edentulous mandibular areas of 5 American fox hounds. Implant groups A, B, and C had a microgap between the implant-abutment connection of <10 microm, 50 microm, or 100 microm, respectively, as did groups D, E, and F, respectively. Abutments were either welded (1 -piece) in groups A, B, and C or non-welded (2-piece screwed) in D, E, and F. All abutment interfaces were placed 1 mm above the alveolar crest. Radiographic assessment was undertaken to evaluate peri-implant crestal bone levels at baseline and at 1, 2, and 3 months after implant placement whereupon all animals were sacrificed. RESULTS: The size of the microgap at the abutment/implant interface had no significant effect upon crestal bone loss. At 1 month, most implants developed crestal bone loss compared with baseline levels. However, during this early healing period, the non-welded group (D, E, and F) showed significantly greater crestal bone loss from baseline to one month (P <0.04) and 2 months (P < 0.02) compared with the welded group (A, B, and C). No significant differences were observed between these 2 groups at 3 months (P > 0.70). CONCLUSIONS: Crestal bone loss was an early manifestation of wound healing occurring after 1 month of implant placement. However, the size of the microgap at the implant-abutment interface had no significant effect upon crestal bone resorption. Thus, 2-piece non-welded implants showed significantly greater crestal bone loss compared with 1-piece welded implants after 1 and 2 months suggesting that the stability of the implant/abutment interface may have an important early role to play in determining crestal bone levels. At 3 months, this influence followed a similar trend but was not observed to be statistically significant. This finding implies that implant configurations incorporating interfaces will be associated with biological changes regardless of interface size and that mobility between components may have an early influence on wound healing around the implant.

Factors that modulate the effects of bone morphogenetic protein-induced periodontal regeneration: a critical review.

The healing process initiated by a single molecular species of bone morphogenetic protein (BMP) such as BMP-2 or BMP-7 sets in motion a cascade of cellular events resulting in differentiation of progenitor cells into phenotypes involved in periodontal regeneration. For example, animal studies show that a single dose of recombinant human (rh) BMP-2 increases the rate of normal intramembranous bone formation and enhanced cementum formation during periodontal wound healing. However, the optimal effects of BMPs are modulated by a range of factors that need careful evaluation in clinical studies. These factors include the influence of root conditioning, occlusal loading, BMP dose, and the release characteristics of the carrier as well as the suitability of the model to evaluate the efficacy of BMPs. Each of these factors may affect the rate of BMP-induced osteogenesis and cementogenesis and subsequent periodontal ligament (PDL) formation during the early and late stages of periodontal wound healing. Although BMP-2 initiates stem cells along an osteogenic pathway, the dose may have to be of sufficient concentration to ensure other growth and differentiation factors do not redirect or retard the osteogenic potential of the cell. Understanding when to manipulate the cell's differentiation pathway with the application of single or multiple doses of BMPs at the appropriate concentration is required to optimize the effect of BMPs in periodontal wound healing. Therefore, different release profiles from the same carrier may be particularly important in tissues with mixed cell populations such as in the periodontium, where similar tissues like bone and cementum grow at different rates. Furthermore, treatment of intrabony defects with BMPs are likely to not only require appropriate temporal release of the BMP(s), but also a carrier that can serve as a template for new tissue formation providing space maintenance and supporting the mucoperiosteal flap. Many of these issues have not been adequately addressed from a periodontal standpoint; therefore the purpose of this review is to clarify our current understanding of the factors that are likely to modulate the effects of BMP-induced periodontal regeneration. Moreover, assessing the importance of these factors is essential prior to conducting expensive human clinical trials.