Foundations Of Periodontics For The Dental Hygienist Case Study Answers

12.2

Periodontal Defects

Periodontal disease is characterized as a chronic bacterial infection which affects the gums and the bone supporting the teeth. Very often, surgical regenerative procedures are needed to treat the condition. According to the American Academy of Periodontology, periodontal regeneration includes the regeneration of cementum, functionally aligned periodontal ligament, alveolar bone and gingiva [1]. In 1996, the FDA approved Emdogain®, an embryonic enamel matrix derivative (EMD) device containing amelogenins extracted from six-month-old piglets [2]. This EMD is indicated for treatment of intrabony defects without furcations (resulting from moderate or severe periodontitis), by topical application onto surgically exposed root surfaces. Amelogenins are a family of hydrophobic proteins (due to their high proline, histidine, glutamine and leucine content) that represent approximately 90% of the organic constituent of the enamel matrix [3]. In Emdogain®, amelogenins which have been stabilized by heat treatment are dissolved in an acidic solution of polyethylene glycol alginate (PGA) and supplied in a pre-filled syringe (30 mg protein/ml PGA). The thixotropic rheology (the ability of a fluid to suffer a decrease in viscosity with time when subjected to constant shear) of PGA allows the application of the proteins as a viscous formulation (2.5 Pa). Moreover, upon application of a shear force (by means of the syringe in which the device is supplied), the viscosity of the formulation decreases, thus facilitating the coating of the surgically exposed root surfaces [4]. During application, physiological conditions will cause a decrease in viscosity and an increase in pH, which in turn causes the amelogenins to precipitate, forming a matrix on the root surface.

In vitro, EMD has been shown to enhance the proliferation, total protein synthesis and mineralized nodule formation of periodontal ligament (PDL) cells, while having no significant effect on cell migration, attachment and spreading [5]. In another study, the application of high doses of EMD had a detrimental effect on the viability of human periodontal ligament fibroblasts (PDLF); however, cellular proliferation appeared to be improved following exposure, as well as cellular attachment to diseased root surfaces [6]. It has also been suggested that EMD has the potential to direct the differentiation of a mesenchymal pluripotential cell line (C2C12) to osteoblasts or chondroblasts [7], and its regulatory role on cementoblast and osteoblast activities has also been documented [8]. Moreover, the ability of EMD to promote periodontal regeneration may also be related to its ability to reduce dental plaque: EMD has an inhibitory effect on the growth of periodontal gram-negative pathogens (which are associated with reduced wound healing), whilst having no significant effect on gram-positive bacteria [9].

In preclinical animal models, EMD has been found to promote the regeneration of all periodontal tissues, namely acellular cementum, periodontal ligaments and alveolar bone [10]. In particular, EMD has the potential to increase the osteoinductive properties of the graft material [11]. For example, when EMD was administered together with demineralized freeze-dried bone allograft (DFDBA) above a certain threshold concentration in a nude mouse muscle implantation assay, osteoinduction was enhanced. In a rat femur drill-hole injury model, locally applied EMD significantly increased the volume of newly formed bone trabeculae when compared to the blank vehicle [12]. These studies demonstrate that, in addition to stimulatory effects on bone growth, EMD has both osteoconductive and cementoconductive properties. In clinical trials, the following inferences can be drawn:

(i)

the periodontal regeneration promoted by EMD is only observed when surgical treatment of deep intrabony defects is performed;

(ii)

the combination of EMD and periodontal surgery of deep intrabony defects leads to significantly higher improvements in clinical parameters when compared to open flap debridement alone;

(iii)

the combination of EMD and guided tissue regeneration (GTR) does not improve the outcomes when compare to EMD or GTR alone;

(iv)

the combination of EMD with some types of bone graft/substitute can result in the improvement of certain parameters, compared to EMD treatment alone;

(v)

the combination of EMD and coronally repositioned flaps on the treatment of recession-type defects may promote formation of cementum and bone;

(vi)

the application of EMD may improve periodontal regeneration in mandibular class II bifurcations [13].

In June 2009, Emdogain® received FDA approval, for use in conjunction with bone substitute materials and also for the treatment of gingival recession defects.

In 2005, the FDA approved a bone grafting material containing a biological therapeutic agent, named GEM21S™ (Growth Factor Enhanced Matrix), to treat periodontal-related defects, such as intrabony, furcation and gingival recession [14]. The GEM21S device comprises two components:

(i)

a synthetic, highly porous (pore diameter 1 to 500 μm) and resorbable beta-tricalcium phosphate (β-TCP) scaffold, to provide a matrix for bone growth, prevent the collapse of soft tissues and promote the stabilization of the blood clot;

(ii)

purified recombinant human platelet-derived growth factor-BB (rhPDGF-BB), a growth factor that is released at the site of injury during blood clotting, to act as a chemoattractant and mitogen for mesenchymal cells (including osteogenic cells) and promote angiogenesis [15].

The β-TCP particles (0.25 to 1 mm in diameter) are supplied sterile in a “cup”, with the rhPDGF-BB supplied as a sterile 0.5 ml solution (0.3 mg/ml, in 20 mM sodium acetate buffer, pH 6). Both components are stored under refrigeration and have a shelf life of 36 months. Prior to application, the β-TCP particles are transferred to the cup, in an aseptic environment, before addition of the rhPDGF-BB solution. Upon saturation of the β-TCP particles with the rhPDGF-BB solution, the mixture is rested for 10 minutes to completely hydrate the β-TCP particles and entrap the rhPDGF-BB within the pores; this in turn facilitates a more uniform distribution of the growth factor at the implant location. It has been shown both in vitro and in vivo that the growth factor is rapidly released from the particles, and that the non-specific adsorption has no effect on its structural integrity and biological activity [16]. In a large, multicenter, randomized, controlled trial, the following treatments were used for advanced periodontal osseous defects:

(i)

β-TCP + 0.3 mg/ml rhPDGF-BB in buffer;

(ii)

β-TCP + 1.0 mg/ml rhPDGF-BB in buffer; and

(iii)

b-TCP + buffer (active control).

Clinical attachment levels (CAL), gingival recession (GR), linear bone growth (LBG) and percentage bone fill (% BF) were assessed [17]. After six months of healing, an improvement in the clinical outcomes was observed for both test and active control treatments. The rate of gain in CAL at 3 months appeared to be more rapid in the β-TCP + 0.3 mg/ml rhPDGF-BB group than in the control group, although no significant differences were found. The improvement in LB and % BF was significantly higher for the β-TCP + 0.3 mg/ml rhPDGF-BB group when compared to the other groups, supporting the rationale for the clinical use of this concentration of growth factor. The classification of this type of peptide formulation as a medical device has been the subject of discussion, since the same peptide is also commercialized in a different formulation as a human medicine.

Эти числа отлично работают при создании шифров, потому что компьютеры не могут угадать их с помощью обычного числового дерева.

Соши даже подпрыгнула. - Да. Совершенно верно. Простые числа играют важнейшую роль в японской культуре.

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