A Sewing Approach to the Fabrication of Eco/bioresorbable Electronics.

Eco/bioresorbable electronics represent an emerging class of technology defined by an ability to dissolve or otherwise harmlessly disappear in environmental or biological surroundings after a period of stable operation. The resulting devices provide unique capabilities as temporary biomedical implants, environmental sensors, and related systems. Recent publications report schemes to overcome challenges in fabrication that follow from the low thermostability and/or high chemical reactivity of the eco/bioresorbable constituent materials. Here, this work reports the use of high-speed sewing machines, as the basis for a high-throughput manufacturing technique that addresses many requirements for these applications, without the need for high temperatures or reactive solvents. Results demonstrate that a range of eco/bioresorbable metal wires and polymer threads can be embroidered into complex, user-defined conductive patterns on eco/bioresorbable substrates. Functional electronic components, such as stretchable interconnects and antennas are possible, along with fully integrated systems. Examples of the latter include wirelessly powered light-emitting diodes, radiofrequency identification tags, and temporary cardiac pacemakers. These advances add to a growing range of options in high-throughput, automated fabrication of eco/bioresorbable electronics.

Endotoxin tolerance induced by Porphyromonas gingivalis lipopolysaccharide alters macrophage polarization.

Endotoxin tolerance refers to a state refractory to subsequent lipopolysaccharide (LPS) stimulations following a primary LPS exposure. To study the relationship between endotoxin tolerance and macrophage polarization, endotoxin tolerance was induced by 1 µg/mL LPS from the periodontal pathogen, Porphyromonas gingivalis (P. gingivalis), in peritoneal macrophages (PMs) and bone marrow-derived macrophages (BMDMs). Repeated P. gingivalis LPS challenges increased the quantities of CD206+ PMs, while the number of CD86+CD206+ PMs was reduced compared with the non-tolerant group (p < 0.05). However, there were no changes in BMDMs (p > 0.05). Down regulations of TNF-α, IL-12, nitric oxide and MMP-2 production, and upregulated IL-10, MMP-9 levels and arginase-1 activities occurred in tolerant PMs and BMDMs (p < 0.05). P. gingivalis LPS-tolerant PMs and BMDMs also enhanced scrape-wound healing abilities of 15p-1 cells (p < 0.05). Expressions of phospho-signal transducer and activator of transcription 6 (p-STAT6) and protein tyrosine phosphatase 1B (PTP1B) were increased, while p-MEK1/2 levels were downregulated in tolerant PMs and BMDMs (p < 0.05). IL-10 production in tolerant Stat6 knockdown RAW264.7 cells was lower than tolerant control cells (p < 0.05). P. gingivalis LPS-tolerant macrophages represented an intermediate state between M1/M2 polarization, which functioned as M2-like cells, and led to limited inflammatory responses and enhanced wound healing activities. The PTP1B-MEK1/2-STAT6 signaling pathway might be involved in the polarization of tolerant macrophages.

Dietary nitrate improves jaw bone remodelling in zoledronate-treated mice.

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a serious complication that occurs in patients with osteoporosis or metastatic bone cancer treated with bisphosphonate. There is still no effective treatment and prevention strategy for BRONJ. Inorganic nitrate, which is abundant in green vegetables, has been reported to be protective in multiple diseases. To investigate the effects of dietary nitrate on BRONJ-like lesions in mice, we utilized a well-established mouse BRONJ model, in which tooth extraction was performed. Specifically, 4 mM sodium nitrate was administered in advance through drinking water to assess the short- and long-term effects on BRONJ. Zoledronate injection could induce severe healing inhibition of the tooth extraction socket, while addition of pretreating dietary nitrate could alleviate the inhibition by reducing monocyte necrosis and inflammatory cytokines production. Mechanistically, nitrate intake increased plasma nitric oxide levels, which attenuated necroptosis of monocytes by downregulating lipid and lipid-like molecule metabolism via a RIPK3 dependent pathway. Our findings revealed that dietary nitrate could inhibit monocyte necroptosis in BRONJ, regulate the bone immune microenvironment and promote bone remodelling after injury. This study contributes to the understanding of the immunopathogenesis of zoledronate and supports the feasibility of dietary nitrate for the clinical prevention of BRONJ.

Effects of Endotoxin Tolerance Induced by Porphyromonas gingivalis Lipopolysaccharide on Inflammatory Responses in Neutrophils.

Periodontitis is a dental plaque-induced chronic inflammatory disease. Long-term exposure of the host to periodontal pathogens leads to a hyporesponsive state to the following stimulations, which is described as endotoxin tolerance. Neutrophils are the most abundant innate immune cells in the body. To clarify the roles of endotoxin tolerance in periodontitis, inflammatory responses in Porphyromonas gingivalis (P. gingivalis) lipopolysaccharide (LPS)-tolerized neutrophils were explored in this study. Here, apoptosis and respiratory burst in neutrophils upon single or repeated P. gingivalis LPS stimulations were explored by flow cytometry. Cytokine production (TNF-α, IL-8, and IL-10) in tolerized neutrophils or neutrophils co-cultured with peripheral blood mononuclear cells was determined by ELISA. Phagocytosis of P. gingivalis by tolerized neutrophils was also assayed by flow cytometry. In addition, quality and quantitation of neutrophil extracellular trap (NET) formation were detected using immunofluorescence microscope and microplate reader, respectively. The protein expressions of extracellular signal-regulated kinase1/2 (ERK1/2), c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase (p38 MAPK) were examined to identify possible mechanisms for the abovementioned changes. Tolerance induced by P. gingivalis LPS significantly suppressed apoptosis, reactive oxygen species (ROS) generation, and phagocytosis in neutrophils (p < 0.05). In both neutrophils alone and co-culture system, repeated P. gingivalis LPS stimulations significantly decreased TNF-α production, but increased IL-10 secretion (p < 0.05). Moreover, in tolerized neutrophils, NET formations were strengthened and there were more released extracellular DNA (p < 0.05). In P. gingivalis LPS-tolerized neutrophils, phosphorylation of ERK1/2 was suppressed compared with that in non-tolerized cells. Taken together, immune responses in neutrophils were reprogrammed by P. gingivalis LPS-induced tolerance, which might be related with the development of inflammation in periodontal tissues. Moreover, ERK1/2 might play important roles in endotoxin tolerance triggered by P. gingivalis LPS.

Assessment of Periodontal Biotype in a Young Chinese Population using Different Measurement Methods.

Periodontal biotype is used to describe the morphological characteristics of periodontal tissues and is closely related to periodontal health and prognosis of many dental treatments. This study was undertaken to explore the periodontal biotype distribution in a young Chinese population and to evaluate the accuracy of different methods for gingival thickness (GT) measurement. A total of 372 teeth from 31 periodontally healthy subjects were included. GT was measured simultaneously by probe transparency, transgingival probing and cone-beam computed tomography (CBCT). Some other anatomic parameters, including crown width/crown length ratio, attached gingival width, labial bone thickness and papilla volume were recorded for periodontal biotype classification. As found by probe transparency, the gingivae of 222 teeth (59.68%) were thick, while those of 150 teeth (40.32%) were thin. The mean GT of included subjects was 1.03 ± 0.31 mm as measured by transgingival probing and 1.03 ± 0.24 mm as measured by CBCT. Four groups were identified by cluster analysis. Thick-flap biotype, average-scalloped biotype, average-flap biotype and thin-scalloped biotype comprised 137 teeth (36.83%), 96 teeth (25.81%), 39 teeth (10.48%) and 100 teeth (26.88%), respectively. These results demonstrate that the most common periodontal biotype in this young Chinese population was the thick-flap type with low aesthetic risk.

Tolerance induced by Porphyromonas gingivalis may occur independently of TLR2 and TLR4.

OBJECTIVE: Periodontitis is a microbe-induced chronic inflammatory disease. Previous exposure of the host to bacteria or their virulence factors leads to refractory responses to further stimuli, which is called tolerance. Porphyromonas gingivalis (P. gingivalis) is one of the most important pathogenic microorganisms associated with periodontitis, and is a potent inducer of pro- and anti-inflammatory cytokines. The aim of this study was to explore the roles and possible mechanisms of tolerance induced by P. gingivalis. METHODS: THP-1-derived macrophages were pretreated with 1x108 colony-forming units/ml P. gingivalis ATCC 33277 or 21 clinical isolates from moderate to severe chronic periodontitis patients (24 h), washed (2 h) and treated with P. gingivalis ATCC 33277 or the same clinical isolates again (24 h). Levels of pro-inflammatory cytokines TNF-α and IL-1ß and anti-inflammatory cytokine IL-10 in supernatants were detected by ELISA. Moreover, to identify the possible mechanisms for the changes in cytokine secretion, Toll-like receptor 2 (TLR2) and TLR4 protein expressions were explored in these cells by flow cytometry. RESULTS: After repeated challenge with P. gingivalis ATCC 33277 or clinical isolates, production of TNF-α and IL-1ß in macrophages was decreased significantly compared with that following a single stimulation (p<0.05), while only comparable levels of IL-10 were detected in P. gingivalis ATCC 33277 or clinical isolate-tolerized cells (p>0.05). In addition, there was interstrain variability in the ability to induce IL-1ß and IL-10 production after repeated P. gingivalis stimulation. However, no significant changes in TLR2 or TLR4 were detected in macrophages that were repeatedly treated with P. gingivalis ATCC 33277 or clinical isolates compared with those stimulated with P. gingivalis only once (p>0.05). CONCLUSIONS: Repeated P. gingivalis stimulation triggered tolerance, which might contribute to limiting periodontal inflammation. However, tolerance induced by P. gingivalis might develop independently of TLR2 and TLR4 and be related to molecules in signaling pathways downstream of TLR2 and TLR4.