We found evidence for beneficial effects of PRP in the treatment of periodontal defects. Evidence for beneficial effects of PRP in sinus elevation appeared to be weak. No conclusions can be drawn about other applications of PRP in dentistry.
Local drug delivery systems have recently been developed for multiple diseases that have the requirements of site‐specific actions, prolonged delivery periods, and decreased drug dosage to reduce undesirable side effects. The challenge for such systems is to achieve directional and precise delivery in inaccessible narrow lesions, such as periodontal pockets or root canals in deeper portions of the dentinal tubules. The primary strategy to tackle this challenge is fabricating a smart tracking delivery system. Here, drug‐loaded biodegradable micromotors showing self‐propelled directional movement along a hydrogen peroxide concentration gradient produced by phorbol esters‐stimulated macrophages are reported. The drug‐loaded poly(lactic‐co‐glycolic acid) micromotors with asymmetric coverage of enzyme (patch‐like enzyme distribution) are prepared by electrospraying and postfunctionalized with catalase via 1‐ethyl‐3‐(3‐dimethylaminopropyl) carbodiimide coupling. Doxycycline, a common drug for the treatment of periodontal disease, is selected as a model drug, and the release study by high‐performance liquid chromatography is shown that both the postfunctionalization step and the presence of hydrogen peroxide have no negative influence on drug release profiles. The movement behavior in the presence of hydrogen peroxide is confirmed by nanoparticle tracking analysis. An in vitro model is designed and confirmed the response efficiency and directional control of the micromotors toward phorbol esters‐stimulated macrophages.
A 6.2 mm cranial defect is not a critical-sized defect in rats. Rat PRP had no effect on the early stages of bone healing in addition to an osteoconductive material. Dense HA/beta-TCP particles showed a beneficial effect on bone formation already after 1 and 2 weeks of implantation in non-critical-sized cranial defects in rats.
The effect of platelet-rich plasma (PRP) on bone regeneration, in combination with an osteoconductive material, was evaluated in a rat model. Cranial defects, 6.2 mm in diameter, were filled with HA/beta-TCP particles, HA/beta-TCP particles combined with PRP and HA/beta-TCP particles combined with PRP gel, where some were left empty as a control. After 4 weeks of implantation histological, histomorphometrical and micro-computed tomography analyses revealed no difference in new bone formation among the groups. Further, no additional effect of PRP gel in comparison with PRP liquid was detected, except for the increased handling capacity of the graft. These findings suggest that PRP had no positive effect on bone formation in addition to an osteoconductive material after an implantation period of 4 weeks. Also, no negative effect was seen, and neither PRP nor HA/beta-TCP hampered bone ingrowth into the defects.
The aim of this study was to examine the bone augmentation properties of an injectable composite consisting of PLGA microspheres/CaP cement (20/80), and the additional effect of loading PLGA microspheres with TGF-beta1 (200 ng). For this purpose, PLGA/CaP composites (control) and PLGA/CaP composites loaded with TGF-beta1 (test group) were injected on top of the skulls of 24 Wistar rats. Each rat received 2 materials from the same experimental group, and in total 48 implants were placed (n = 8). After 2, 4, and 8 weeks the results were evaluated histologically and histomorphometrically. The contact length between the implants and newly formed bone increased in time, and was significantly higher for the TGF-beta1-loaded composites after 2 weeks. Also, bone formation was significantly higher for the TGF-beta1-loaded composites (18.5% +/- 3) compared to controls (7.21% +/- 5) after 8 weeks of implantation. Immunohistochemical staining demonstrated massive inflammatory infiltrates in both groups, particularly at 2 weeks, which decreased substantially at 4 and 8 weeks. In conclusion, injectable PLGA/CaP composites stimulated bone augmentation in a rat model. The addition of TGF-beta1 to the composite significantly increased bone contact at 2 weeks and enhanced new bone formation at 8 weeks.
Systemic inflammation induced by periodontitis is suggested to be the link between periodontitis and cardiovascular disease. The aim of this work was to explore the oral microbiome in periodontitis in relation to disease severity and systemic inflammation. The saliva and subgingival microbiome from periodontal pocket samples of patients with severe (n = 12) and mild periodontitis (n = 13) were analyzed using metagenomic shotgun sequencing. The taxa and pathways abundances were quantified. The diversity was assessed and the abundances to phenotype associations were performed using ANCOM and linear regression. A panel of inflammatory markers was measured in blood and was associated with taxa abundance. The microbial diversity and species richness did not differ between severe and mild periodontitis in either saliva or periodontal pockets. However, there were significant differences in the microbial composition between severe and mild periodontitis in the subgingival microbiome (i.e., pocket samples) and, in a lower grade, in saliva, and this is positively associated with systemic inflammatory markers. The “red complex” and “cluster B” abundances in periodontal pockets were strongly associated with inflammatory markers interleukin-6 and the white blood cell count. Our data suggest that systemic inflammation in severe periodontitis may be driven by the oral microbiome and may support the indirect (inflammatory) mechanism for the association between periodontitis and cardiovascular disease.
With currently available therapies, full regeneration of lost periodontal tissues after periodontitis cannot be achieved. In this study, a combined compartmentalized system was tested, composed of (a) a platelet lysate (PL)-based construct, which was placed along the root aiming to regenerate the root cementum and periodontal ligament, and (b) a calcium phosphate cement composite incorporated with hyaluronic acid microspheres loaded with PL, aiming to promote the regeneration of alveolar bone. This bilayered system was assessed in a 3-wall periodontal defect in Wistar rats. The periodontal healing and the inflammatory response of the materials were scored for a period up to 6 weeks after implantation. Furthermore, histomorphometrical measurements were performed to assess the epithelial downgrowth, the formation of alveolar bone, and the formation of new connective tissue attachment. Our data showed that the stabilization of platelet-origin proteins on the root surface increased the overall periodontal healing score and restricted the formation of long epithelial junctions. Nevertheless, the faster degradation of the cement component with incorporated hyaluronic acid microspheres compromised the stability of the system, which hampered the periodontal regeneration. Overall, in this work, we proved the positive therapeutic effect of the immobilization of a PL-based construct over the root surface in a combined compartmentalized system to assist predictable healing of functional periodontium. Therefore, after optimization of the hard tissue analogue, the system should be further elaborated in (pre)clinical validation studies.
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