Platelet-derived growth factor stimulates bone fill and rate of attachment level gain: results of a large multicenter randomized controlled trial

BACKGROUND: Growth factors are generally accepted to be essential mediators of tissue repair via well-established mechanisms of action that include stimulatory effects on angiogenesis and cellular proliferation, ingrowth, differentiation, and matrix biosynthesis. The aim of this study was to evaluate in a large-scale, prospective, blinded, and randomized controlled clinical trial the safety and effectiveness of purified recombinant human platelet-derived growth factor (rhPDGF-BB) mixed with a synthetic beta-tricalcium phosphate (beta-TCP) matrix for the treatment of advanced periodontal osseous defects at 6 months of healing. METHODS: Eleven clinical centers enrolled 180 subjects, each requiring surgical treatment of a 4 mm or greater intrabony periodontal defect and meeting all inclusion and exclusion criteria. Subjects were randomized into one of three treatment groups: 1) beta-TCP + 0.3 mg/ml rhPDGF-BB in buffer; 2) beta-TCP + 1.0 mg/ml rhPDGF-BB in buffer; and 3) beta-TCP + buffer (active control). Safety data were assessed by the frequency and severity of adverse events. Effectiveness measurements included clinical attachment levels (CAL) and gingival recession (GR) measured clinically and linear bone growth (LBG) and percent bone fill (% BF) as assessed radiographically by an independent centralized radiology review center. The area under the curve (AUC), an assessment of the rate of healing, was also calculated for CAL measurements. The surgeons, clinical and radiographic evaluators, patients, and study sponsor were all masked with respect to treatment groups. RESULTS: CAL gain was significantly greater at 3 months for group 1 (rhPDGF 0.3 mg/ml) compared to group 3 (beta-TCP + buffer) (3.8 versus 3.3 mm; P = 0.032), although by 6 months, this finding was not statistically significant (P = 0.11). This early acceleration of CAL gain led to group 1 exhibiting a significantly greater rate of CAL gain between baseline and 6 months than group 3 as assessed by the AUC (68.4- versus 60.1-mm weeks; P = 0.033). rhPDGF (0.3 mg/ml)-treated sites also had significantly greater linear bone gain (2.6 versus 0.9 mm, respectively; P < 0.001) and percent defect fill (57% versus 18%, respectively; P < 0.001) than the sites receiving the bone substitute with buffer at 6 months. There was less GR at 3 months in group 1 compared to group 3 (P = 0.04); at 6 months, GR for group 1 remained unchanged, whereas there was a slight gain in gingival height for group 3 resulting in comparable GR. There were no serious adverse events attributable to any of the treatments. CONCLUSIONS: To our knowledge, this study is the largest prospective, randomized, triple-blinded, and controlled pivotal clinical trial reported to date assessing a putative periodontal regenerative and wound healing therapy. The study demonstrated that the use of rhPDGF-BB was safe and effective in the treatment of periodontal osseous defects. Treatment with rhPDGF-BB stimulated a significant increase in the rate of CAL gain, reduced gingival recession at 3 months post-surgery, and improved bone fill as compared to a beta-TCP bone substitute at 6 months.     

Template fabrication for a midpalatal orthodontic implant: technical note

An implant has been developed as an adjunct to conventional orthodontic anchorage. Planning is advisable to determine the available bone and soft tissue thickness and the optimum position for orthodontic utilization. A simple method is described for fabrication of a radiographic and surgical template to aid in optimal placement of the implant.     

Assay of bone morphogenetic protein-2, -4, and -7 in human demineralized bone matrix

Demineralized bone matrix (DBM) is a widely used bone graft material that derives its osteoinductive potential from matrix-associated bone morphogenetic proteins (BMPs). Prior investigations have shown that the osteoinductive potential can vary widely, with influence from both donor and processing sources. Although it is plausible that donor variance in the BMP profile can be an important consideration, the few published studies available have given inconsistent and incomplete information about this. The goal was to (1) characterize the variance of BMP-2, BMP-4, and BMP-7 in fully demineralized DBM derived from 20 appropriately screened (Food and Drug Administration and the American Association of Tissue Banks criteria) donors (male and female, 17-65 years) and (2) using literature review, infer the potential for this to be an important source of variability in graft function. BMPs were extracted with 4 M guanidine hydrochloride, and levels of BMP-2, BMP-4, and BMP-7 were measured using enzyme-linked immunosorbent assay. Measured levels were as follows: BMP-2 = 21.4 +/- 12.0 ng/g DBM, BMP-4 = 5.45 +/- 2.04 ng/g DBM, and BMP-7 = 84.1 +/- 34.4 ng/g DBM, which were significantly different (P < 0.05). There was a positive linear correlation between BMP-2 and BMP-7 (P = 0.0227). DBM derived from female donors had significantly greater concentrations of BMP-2 and BMP-7 than did that derived from male donors (P = 0.0257 and 0.0245, respectively). There was no significant correlation between donor age and the levels of any of the measured BMPs. The magnitude of variance of BMP profile appears to reasonably well correspond to the variance in osteoinductive potential cited by others, suggesting the possibility of using this as a method of donor screening.     

Viscoelastic behavior and fracture toughness of six glass-ionomer cements

STATEMENT OF PROBLEM: Viscoelastic behavior can influence the fracture properties of glass ionomers, which is of clinical relevance. Glass-ionomer cements can display viscoelastic behavior, defined as having displacement rate- or strain rate-dependent mechanical properties. Understanding and describing the viscoelastic behavior of glass ionomers is important to understanding their clinical behavior. PURPOSE: The purpose of this study was to evaluate the viscoelastic behavior of 6 glass-ionomer cements and determine whether there was a correlation to fracture toughness. MATERIAL AND METHODS: Three conventional glass-ionomer cements (alpha-Silver, alpha-Fil, and Ketac-Molar) and 3 resin-modified glass-ionomer cements (Vitremer, Fuji II LC, and Photac-Fil Quick) were evaluated using measurements of compressive strength (CS), flexural strength (FS), and diametral tensile strength (DTS) at displacement rates of 0.5, 1.0, 1.5, and 2.0 mm/min. The CS and DTS specimens were cured in glass tubes and cut to 4 x 6-mm and 4 x 2-mm disk-shaped specimens, respectively. The FS specimens were cured in bar molds (2 x 2 x 15 mm). The fracture toughness (FT) specimens were cured in a minicompact mold to obtain precracked specimens. The mechanical testing results were compared statistically using generalized linear model/analysis of covariance and the Ryan-Einot-Gabriel-Welsch multiple range test at the alpha=.05 level. RESULTS: For all 3 mechanical properties, there was a displacement-rate dependence on the mechanical property. However, there were no differences in the displacement-rate dependence based on the type of material-conventional glass ionomer or resin-modified glass ionomer-for any of the mechanical properties. Only for FS test was there a significant difference based on the brand of material. There was no statistical difference in FT among the glass-ionomer cements tested, although the resin-modified glass ionomers tended to display higher FT. CONCLUSION: A larger sample size and a much wider range of crosshead speeds are necessary to support a correlation between viscoelastic behavior and FT.     

Repair of alveolar clefts with recombinant human bone morphogenetic protein (rhBMP-2) in patients with clefts

This article demonstrates the feasibility of using recombinant human bone morphogenetic protein (rhBMP-2) as a substitute for autogenous iliac crest bone for repair of congenital facial clefts in humans. In this series, 50 cleft sites were repaired in 43 patients using rhBMP-2 without the use of autogenous graft tissue. Successful osseous union was achieved in 49 of the 50 sites. In one patient, the graft failed to consolidate. Severe clefts were managed by combining distraction osteogenesis and rhBMP-2. Eliminating the need to harvest autogenous iliac crest bone resulted in substantial decrease in morbidity. The constructed alveolus performed clinically as normal bone and responded to natural tooth eruption and orthodontic movement. Histology of the tissue constructed showed normal, vital bone. Although additional investigation is warranted to determine the optimum protocol for the use of this material in alveolar cleft repair, the technique should be considered as a viable treatment option in cases in which avoiding iliac crest harvesting is desirable.     

牙周临床治疗Ⅵ.牙周病药物治疗的理念

菌斑微生物是牙周病的始动因子，微生物及其毒性产物可引发局部及全身的一系列宿主免疫、炎症反应，宿主具有多层屏障的防御机制，对感染的应答基本上是保护性的，但反应过强或过弱，均可能发病。因此，微生物与宿主间的相互作用决定了疾病的过程和进展。针对病因的治疗，使我们在机械清除菌斑之外，也可能采用药物辅助手段清除致病微生物、阻断宿主反应的破坏过程、调节宿主的自身免疫力，以达到治疗目的。目前，牙周病的药物治疗主要是针对微生物的，对宿主反应的调节尚不够成熟。     

复方甲硝唑缓释膜剂的研制及应用

本文研制了治疗牙周炎的复方甲硝唑缓释膜剂.为证实其对牙周病的治疗作用,进行了体外抑菌试验和临床应用.结果表明,该缓释膜剂对牙周病优势菌有明显抑制效果;经临床观察使用该药膜一周后,菌斑指数(PLI)、牙龈指数(GI)、龈沟出血指数(SBI)及牙周袋深度(PD)均显著降低,证明复方甲硝唑缓释膜剂治疗牙周病有广阔前景.     

Histomorphometric analysis of rat alveolar wound healing with hydroxyapatite alone or associated to BMPs

Several materials and techniques have been proposed to improve alveolar wound healing and decrease loss of bone height and thickness that normally follow dental extraction. The objective of this research was the histologic analysis of bone morphogenetic proteins implanted into dental alveoli of rats after extraction. A total of 45 adult male Wistar rats were divided into three groups of 15 animals each: control (no treatment), implanted with pure hydroxyapatite (HA, 3 mg) and implanted with hydroxyapatite plus bone morphogenetic proteins (HA/BMPs, 3 mg). Five animals from each group were sacrificed at 7, 21 and 42 days after extraction for the histometric analyses of the osteoconductive potential of hydroxyapatite associated or not with BMPs. After dissection, fixation, decalcification and serial microtomy of 6-micron thick sections, the samples were stained with hematoxylin-eosin for histologic and histometric analyses. Both HA and HA/BMPs caused a delay in wound healing compared to control animals, evaluated by the percentage of bone tissue in the alveoli. The treatment with HA/BMPs had the greatest delay at 21 days, even though it produced values similar to the control group at 42 days. The materials did not improve alveolar repair in the normal period of wound healing and the association of HA/BMPs did not have osteoconductive properties with granulated hydroxyapatite as the vehicle.