Omar Omar

Background Nonresorbable membranes promote bone formation during guided bone regeneration (GBR), yet the relationships between membrane properties and molecular changes in the surrounding tissue are largely unknown. Aim To compare the molecular events in the overlying soft tissue, the membrane, and the underlying bone defect during GBR using dual‐layered expanded membranes versus dense polytetrafluoroethylene (PTFE) membranes. Materials and Methods Rat femur defects were treated with either dense PTFE (d‐PTFE) or dual‐layered expanded PTFE (dual e‐PTFE) or left untreated as a sham. Samples were collected after 6 and 28 days for gene expression, histology, and histomorphometry analyses. Results The two membranes promoted the overall bone formation compared to sham. Defects treated with dual e‐PTFE exhibited a significantly higher proportion of new bone in the top central region after 28 days. Compared to that in the sham, the soft tissue in the dual e‐PTFE group showed 2‐fold higher expression of genes related to regeneration (FGF‐2 and FOXO1) and vascularization (VEGF). Furthermore, compared to cells in the d‐PTFE group, cells in the dual e‐PTFE showed 2.5‐fold higher expression of genes related to osteogenic differentiation (BMP‐2), regeneration (FGF‐2 and COL1A1), and vascularization (VEGF), in parallel with lower expression of proinflammatory cytokines (IL‐6 and TNF‐α). Multiple correlations were found between the molecular activities in membrane‐adherent cells and those in the soft tissue. Conclusion Selective surface modification of the two sides of the e‐PTFE membrane constitutes a novel means of modulating the tissue response and promoting bone regeneration.

Aim Inflammatory‐regenerative cell interaction is believed to mediate hard tissue formation. This study aimed to investigate the interaction between human inflammatory monocytes with human regenerative fibroblasts after exposure to different calcium silicate materials. Methodology Human monocytes were cultured on three materials, polystyrene (PS), mineral trioxide aggregates (MTA) and biodentine (BD), in the presence or absence of lipopolysaccharide (LPS). Half of the monocyte‐conditioned media (MoCM) of each group was used to analyse inflammatory cytokine secretion, namely TNF‐α, IL‐1β, IL‐1RA and IL‐6. The remaining MoCM was used to culture recipient fibroblasts, measuring the cell number (proliferation) and levels of alkaline phosphatase (differentiation) and lactic acid dehydrogenase (cytotoxicity). Results In absence of LPS, MTA was associated with higher secretion of TNF‐α and lower secretion of IL‐1β, while BD triggered higher secretions of both cytokines when both materials were compared to control (PS). When LPS was added, higher levels of all analysed cytokines were observed in the PS and BD groups, whereas for the MTA group, only TNF‐α and IL‐6 were increased. Fibroblasts responded differently to the MoCM from the different groups, revealing significant increases in proliferation and differentiation capacities, particularly when cultured in CM from monocytes exposed to MTA. The morphological evaluation revealed different patterns of fibroblast shape and spread in the different MoCM groups. Conclusion Calcium silicate materials modulate the monocyte inflammatory response, which subsequently induce differential effects on the recipient fibroblasts. MTA appears to promote the secretion of prodifferentiation signals from the monocytes, which are received by fibroblasts, promoting their proliferation and differentiation. The model represents a promising tool to evaluate the interaction of different cells in response to different materials.

Several factors might influence the duration and efficiency of local anesthesia. This study investigates the effect of habitual caffeine intake on lidocaine action and explores the potential involvement of voltage-gated sodium channels in the interaction effect. Wistar rats were divided into four groups: (i) control (Ctrl), (ii) lidocaine intraplantar injection (LIDO), (iii) habitual caffeine intake (CAF), and (iv) lidocaine intraplantar injection and habitual caffeine intake (LIDO + CAF). Behavioral assessments, consisting of a paw pressure test for mechanical pressure sensation and a paw withdrawal latency test for thermal pain sensation, were performed at 0, 30, 60, and 90 minutes following lidocaine injection and after 10, 11, and 12 weeks of CAF intake. Pressure sensation was significantly reduced in the LIDO + CAF group compared with the control group. Moreover, the LIDO + CAF group exhibited reduced sensation compared to LIDO alone group. The LIDO + CAF combination exerted a synergistic effect at 30 and 60 minutes compared with the control. This synergistic effect was noted at 60 minutes (11 weeks of CAF intake) and at 30 minutes (12 weeks of CAF intake) compared with LIDO alone. Augmented thermal pain-relieving effects were observed in the LIDO + CAF group at all weeks compared to the control group and at 10 weeks compared to LIDO alone group. The molecular analysis of dorsal root ganglia suggested that CAF upregulated the mRNA expression of the Nav1.3, Nav1.7, and Nav1.8 sodium channel subtypes. Chronic caffeine consumption potentiates the local anesthetic action of lidocaine in an experimental animal model through mechanisms that involve the upregulation of voltage-gated sodium channels in the dorsal root ganglia.