The integrity of the peri‐implant soft‐tissue seal is crucial for maintaining peri‐implant tissue health. Whilst the transmucosal component of the restored implant shares some common features with ...teeth, namely the presence of a junctional epithelium and a connective tissue component, there are some important differences. A key difference is the nature of the relationship of the connective tissue with the implant surface, whereby there is ‘adaptation’ of collagen fibers in a parallel orientation in relation to the implant, but insertion of fiber attachment perpendicularly into cementum in the case of teeth. This, combined with reduced cellularity and vascularity in the peri‐implant connective tissue, may make implants more susceptible to disease initiation and progression. Furthermore, the presence of a subgingival connection between the implant and the abutment/restoration poses some specific challenges, and maintaining the integrity of this connection is important in preserving peri‐implant tissue health. Implant design features, such as the nature of the connection between the implant and the abutment, as well as the surface characteristics of the abutment and implants, may influence the maintenance of the integrity of soft tissue around implants. Iatrogenic factors, such as incorrect seating of the abutment and/or the restoration, and the presence of residual subgingival cement, will lead to loss of soft‐tissue integrity and hence predispose to peri‐implant disease.
Since Freud, clinicians have understood that disturbing memories contribute to psychopathology and that new emotional experiences contribute to therapeutic change. Yet, controversy remains about what ...is truly essential to bring about psychotherapeutic change. Mounting evidence from empirical studies suggests that emotional arousal is a key ingredient in therapeutic change in many modalities. In addition, memory seems to play an important role but there is a lack of consensus on the role of understanding what happened in the past in bringing about therapeutic change. The core idea of this paper is that therapeutic change in a variety of modalities, including behavioral therapy, cognitive-behavioral therapy, emotion-focused therapy, and psychodynamic psychotherapy, results from the updating of prior emotional memories through a process of reconsolidation that incorporates new emotional experiences. We present an integrated memory model with three interactive components - autobiographical (event) memories, semantic structures, and emotional responses - supported by emerging evidence from cognitive neuroscience on implicit and explicit emotion, implicit and explicit memory, emotion-memory interactions, memory reconsolidation, and the relationship between autobiographical and semantic memory. We propose that the essential ingredients of therapeutic change include: (1) reactivating old memories; (2) engaging in new emotional experiences that are incorporated into these reactivated memories via the process of reconsolidation; and (3) reinforcing the integrated memory structure by practicing a new way of behaving and experiencing the world in a variety of contexts. The implications of this new, neurobiologically grounded synthesis for research, clinical practice, and teaching are discussed.
Titanium surface mediated immunomodulation may address compromised post-implantation bone healing in diabetes mellitus. To assess in vitro phenotypic changes, M1 and M2 polarised Type 2 diabetic rat ...(Goto Kakizaki, GK) macrophages were cultured on micro-rough (SLA) or hydrophilic nanostructured SLA (modSLA) titanium. The in vivo effects of the SLA and modSLA surfaces on macrophage phenotype, wound-associated protein expression and bone formation were investigated using a critical-sized calvarial defect model. Compared to healthy macrophages, GK M2 macrophage function was compromised, secreting significantly lower levels of the anti-inflammatory cytokine IL-10. The modSLA surface attenuated the pro-inflammatory cellular environment, reducing pro-inflammatory cytokine production and promoting M2 macrophage phenotype differentiation. ModSLA also suppressed gene expression associated with macrophage multinucleation and giant cell formation and stimulated pro-osteogenic genes in co-cultured osteoblasts. In vivo, modSLA enhanced osteogenesis compared to SLA in GK rats. During early healing, proteomic analysis of both surface adherent and wound exudate material showed that modSLA promoted an immunomodulatory pro-reparative environment. The modSLA surface therefore successfully compensated for the compromised M2 macrophage function in Type 2 diabetes by attenuating the pro-inflammatory response and promoting M2 macrophage activity, thus restoring macrophage homeostasis and resulting in a cellular environment favourable for enhanced osseous healing.
Immunomodulatory effects of modified SLA Ti surface on compromised macrophage phenotypic response in Type II diabetes. M0: Unstimulated Macrophage, Pre-Obs: Pre-osteoblasts, Obs: Osteoblasts. Display omitted
Strong electron correlation can induce Mott insulating behaviour and produce intriguing states of matter such as unconventional superconductivity and quantum spin liquids. Recent advances in van der ...Waals material synthesis enable the exploration of Mott systems in the two-dimensional limit. Here we report characterization of the local electronic properties of single- and few-layer 1T-TaSe2 via spatial- and momentum-resolved spectroscopy involving scanning tunnelling microscopy and angle-resolved photoemission. Our results indicate that electron correlation induces a robust Mott insulator state in single-layer 1T-TaSe2 that is accompanied by unusual orbital texture. Interlayer coupling weakens the insulating phase, as shown by reduction of the energy gap and quenching of the correlation-driven orbital texture in bilayer and trilayer 1T-TaSe2. This establishes single-layer 1T-TaSe2 as a useful platform for investigating strong correlation physics in two dimensions.The electrons that contribute to the Mott insulator state in single-layer 1T-TaSe2 are shown to also have a rich variation in their orbital occupation. As more layers are added, both the insulating state and orbital texture weaken.
The emergence of superconductivity and correlated insulators in magic-angle twisted bilayer graphene (MATBG) has raised the intriguing possibility that its pairing mechanism is distinct from that of ...conventional superconductors
, as described by the Bardeen-Cooper-Schrieffer (BCS) theory. However, recent studies have shown that superconductivity persists even when Coulomb interactions are partially screened
. This suggests that pairing in MATBG might be conventional in nature and a consequence of the large density of states of its flat bands. Here we combine tunnelling and Andreev reflection spectroscopy with a scanning tunnelling microscope to observe several key experimental signatures of unconventional superconductivity in MATBG. We show that the tunnelling spectra below the transition temperature T
are inconsistent with those of a conventional s-wave superconductor, but rather resemble those of a nodal superconductor with an anisotropic pairing mechanism. We observe a large discrepancy between the tunnelling gap Δ
, which far exceeds the mean-field BCS ratio (with 2Δ
/k
T
~ 25), and the gap Δ
extracted from Andreev reflection spectroscopy (2Δ
/k
T
~ 6). The tunnelling gap persists even when superconductivity is suppressed, indicating its emergence from a pseudogap phase. Moreover, the pseudogap and superconductivity are both absent when MATBG is aligned with hexagonal boron nitride. These findings and other observations reported here provide a preponderance of evidence for a non-BCS mechanism for superconductivity in MATBG.
Objectives
As biomaterial‐induced modulation of mediators of the immune response may be a potential therapeutic approach to enhance wound healing events, the aim of this study was to delineate the ...effects of titanium surface modification on macrophage phenotype and function.
Material and methods
Rodent bone marrow‐derived macrophages were polarized into M1 and M2 phenotypes and cultured on micro‐rough (SLA) and hydrophilic modified SLA (modSLA) titanium discs. Macrophage phenotype and cytokine secretion were subsequently assessed by immunostaining and ELISA, respectively. Osteoblast gene expression in response to culture in the M1 and M2 macrophage conditioned media was also evaluated over 7 days by RT‐PCR.
Results
M1 macrophage culture on the modSLA surface promoted an M2‐like phenotype as demonstrated by marked CD163 protein expression, Arg1 gene expression and the secretion of cytokines that significantly upregulated in osteoblasts the expression of genes associated with the TGF‐ß/BMP signalling pathway and osteogenesis. In comparison, M2 macrophage culture on SLA surface promoted an inflammatory phenotype and cytokine profile that was not conducive for osteogenic gene expression.
Conclusions
Macrophages are able to alter or switch their phenotype according to the signals received from the biomaterial surface. A hydrophilic micro‐rough titanium surface topography elicits a macrophage phenotype associated with reduced inflammation and enhanced pro‐osteogenic signalling.
Biomaterial-based bone tissue engineering represents a promising solution to overcome reduced residual bone volume. It has been previously demonstrated that gradient and offset architectures of ...three-dimensional melt electrowritten poly-caprolactone (PCL) scaffolds could successfully direct osteoblast cells differentiation toward an osteogenic lineage, resulting in mineralization. The aim of this study was therefore to evaluate the in vivo osteoconductive capacity of PCL scaffolds with these different architectures.
Five different calcium phosphate (CaP) coated melt electrowritten PCL pore sized scaffolds: 250 μm and 500 μm, 500 μm with 50% fibre offset (offset.50.50), tri layer gradient 250-500-750 μm (grad.250top) and 750-500-250 μm (grad.750top) were implanted into rodent critical-sized calvarial defects. Empty defects were used as a control. After 4 and 8 weeks of healing, the new bone was assessed by micro-computed tomography and immunohistochemistry.
Significantly more newly formed bone was shown in the grad.250top scaffold 8 weeks post-implantation. Histological investigation also showed that soft tissue was replaced with newly formed bone and fully covered the grad.250top scaffold. While, the bone healing did not happen completely in the 250 μm, offset.50.50 scaffolds and blank calvaria defects following 8 weeks of implantation. Immunohistochemical analysis showed the expression of osteogenic markers was present in all scaffold groups at both time points. The mineralization marker Osteocalcin was detected with the highest intensity in the grad.250top and 500 μm scaffolds. Moreover, the expression of the endothelial markers showed that robust angiogenesis was involved in the repair process.
These results suggest that the gradient pore size structure provides superior conditions for bone regeneration.
Objectives
This study assessed the effect of titanium surface modification on macrophage phenotype polarization and osseous healing under diabetic conditions.
Materials and methods
Critical‐sized ...calvarial defects were created in healthy and streptozotocin‐induced type I diabetic Sprague‐Dawley rats. Titanium (Ti) discs with either large‐grit sandblasted and acid‐etched micro‐rough (SLA) or hydrophilic‐modified SLA (modSLA) surfaces were used to cover the healing defect for a period of up to 28 days. Samples of the exudate within the calvarial defect and beneath the titanium discs were collected 1, 4 and 7 days post‐surgery for inflammatory cytokine analysis using an ELISA. The macrophage phenotype(s) on the Ti disc surfaces were determined by CD11c+ (M1) and CD163+ (M2) immunofluorescent staining. Samples of the healing defects at days 14 and 28 were also prepared for histomorphometric analysis.
Results
Cytokine levels in the diabetic animals were higher than those of the healthy group throughout the observation period. The modSLA surface significantly reduced MIP‐2 levels at day 1 in both diabetic and healthy animals, and MCP‐1 levels at day 4 in the diabetic animals. Immuno‐fluorescent staining showed that an M2‐like macrophage phenotype was more frequently found on the modSLA surface at day 1 in healthy and day 4 in both healthy and diabetic animals. Histomorphometric analysis showed more new bone formation on the modSLA surface at days 14 and 28 in both groups, although statistically significant differences were only found in the healthy group.
Conclusion
Diabetic conditions greatly increased the expression of proinflammatory cytokines during osseous healing. The modSLA surface was shown to promote an M2‐like macrophage phenotypic response in titanium adherent macrophages despite the significantly elevated inflammatory environment induced by uncontrolled type I diabetes. Modulation of the macrophage phenotype by the modSLA surface in the early healing period was associated with osseous healing under both healthy and uncontrolled diabetic conditions.
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