Tissue Debris Research Articles

Comparative evaluation of clinical efficacy and volumetric changes in pulpectomized primary molars using hand K-file, ProTaper rotary file, and Kedo-SG blue file: an in-vitro cone beam computed tomography analysis.

The accomplishment of a successful pulpectomy depends on multiple factors that involve targeted removal of the causative irritants and soft and hard tissue debris by mechanical and chemical means. Compare and evaluate the efficacy of canal preparation and volumetric filling using conventional files and two rotary file systems using cone beam computed tomography (CBCT). Thirty freshly extracted human primary second molars were randomly divided into three groups of 10 teeth each. After access opening and working length determination, pre-operative volume analysis was done using CBCT. The canals were then instrumented by either hand K-files, ProTaper rotary files or Kedo-SG Blue rotary files. Post-operative volume analysis was performed using CBCT. All the canals were obturated using Metapex and scanned again using CBCT. Mean values of the pre- and post-operative canal volumes were analyzed using one-way Analysis of Variance (ANOVA). Inter- and intra-group volumetric changes were analyzed statistically using a post hoc test. The mean difference in volume after canal preparation and obturation was the highest in the Kedo-SG Blue group, followed by the ProTaper group and the least in the hand K group (p = 0.001). Inter-group comparison showed statistically significant differences between the hand K group and ProTaper group (p = 0.001), the ProTaper group and Kedo-SG Blue group (p = 0.001), and the hand-K group and Kedo-SG Blue group (p = 0.02). The volume of preparation and obturation was the highest using Kedo-SG Blue, followed by the ProTaper file systems.

Major root endodontic treatments: a systematic review

Introduction: In the root canal treatment scenario, irrigation is one of the most important aspects of the biomechanical preparation of the root canal. A condition for successful endodontic retreatment is adequate cleaning of the root canals, therefore, special attention should be paid to the technique used to remove the filling material, the most commonly used being cement, pastes, and gutta-percha cones. Objective: This study aimed to present the main root endodontic treatments to analyze and compare the techniques for removing pulp tissue debris resulting from root preparation and microorganisms from the canals of the root canal system, seeking complete cleaning and asepsis. Methods: The PRISMA Platform systematic review rules were followed. The search was conducted from April to July 2024 in the Scopus, PubMed, Science Direct, Scielo, and Google Scholar databases. The quality of the studies was based on the GRADE instrument and the risk of bias was analyzed according to the Cochrane instrument. Results and Conclusion: 129 articles were found, 39 were evaluated and 21 were included in this systematic review. Considering the Cochrane tool for risk of bias, the global assessment resulted in 25 studies with a high risk of bias and 27 studies that did not meet GRADE. Most studies showed homogeneity in their results, with X2 =91.5% >50%. It was concluded that the system of root canal instrumentation with rotary files maintains the quality of root preparation and, at the same time, reduces the number of files required to obtain a canal, which would consequently reduce the operative time and also considerably reduce the risk of torsion fracture within the root canal than with files. Irrigation plays a fundamental role in the success of endodontic treatment. Although hypochlorite is the most important irrigant solution, no irrigant can perform all the tasks required by irrigation. A detailed understanding of the mode of action of various solutions is important for optimal irrigation. Within the limitations of this study, the use of the self-adjusting file with the combination of EDTA and NaOCl improved Ca(OH)2 removal. Passive ultrasonic irrigation and the self-adjusting file were more effective in removing Ca(OH)2 from the lateral sulci in the apical parts of the root canal than the EndoVac and conventional syringe irrigation systems.

Abstract We066: Macropinocytosis is essential for macrophage activation in acute ischemia.

Macrophages (Mφ) play central roles in inducing the robust inflammatory response to acute ischemia and promoting anti-inflammatory actions necessary for myocardial repair. The broad range of functional repertoire stems from Mφ plasticity dictated by their interaction with the dynamic ischemic milieu. The limited understanding of such interactions contributes to the lack of means to mitigate inflammatory injury in MI patients. We hypothesize that the dynamic Mφ plasma membrane-mediated process macropinocytosis (MP) is essential for Mφ’s activation and function evolvement in ischemia. By MP, Mφs engulf large amounts of soluble contents from the ischemic environment, and the macropinosomes formed from MP become signaling hubs of DAMP (Damage-Associated Molecular Pattern)-PRR (Pattern Recognition Receptor). We aim to determine if ischemia activates MP in Mφs, the signaling pathways that MP promotes, and the role of this process in post-ischemia repair. The rationale is based on our data demonstrating only soluble DAMP (sDAMP), not tissue debris, activates Mφs . We tested our hypothesis using the murine MI model and bone marrow-derived Mφs (BMDM) and used unpaired t-tests for statistical analyses. We uncover that ischemia markedly increases MP in Mφs; blocking MP by the inhibitors or siRNA-mediated knock-down of the Na+H+ exchanger abolished the production of potent cytokines such as IL1β from Mφs in vitro and in vivo . Furthermore, MP activates NF-κB and MAP kinase triggered by sDAMP and ischemia, critical pathways to produce inflammatory cytokine and chemokine. Intriguingly, mTORC1 activation in BMDM and Mφs in the ischemic myocardium depends on MP. These data suggest MP organizes the activation signal and the pathway required for metabolic rewiring in inflammatory Mφs. Suppressing MP at the earlier stage of ischemia (72h) when sDAMP is abundant in the ischemic tissue significantly reduces mortality and improves cardiac function. In conclusion, we identify MP functionalizes the danger signals in bulk and integrates activation signals with metabolic rewiring to promote and sustain the inflammatory function. Targeting MP is better equipped to reduce inflammatory injury as it modifies the dynamic interaction of Mφs with the ischemic environment.

Correlative Raman, Backscattered Electron and X-ray Imaging and Energy Dispersive X-ray Spectrometry Uncovers Unique Chemical Signatures Surrounding Nanoparticles and Wear Debris in Periprosthetic Tissue

Correlative Raman, Backscattered Electron and X-ray Imaging and Energy Dispersive X-ray Spectrometry Uncovers Unique Chemical Signatures Surrounding Nanoparticles and Wear Debris in Periprosthetic Tissue

Effects of the Irrigation Needle Design on Root Canal Disinfection and Cleaning

IntroductionThis ex vivo study evaluated the disinfecting and cleaning effects of root canal preparation using sodium hypochlorite irrigation with 3 different needle designs. MethodsMesial roots from extracted mandibular molars with Vertucci class II configuration were anatomically matched based on micro-computed tomography (micro-CT) analyses and distributed into 3 groups (n = 18/group). The canals were contaminated with a mixed bacterial culture for 30 days and then subjected to preparation using 2.5% sodium hypochlorite irrigation with open-ended flat needle (3 mm short of the working length - WL), closed-ended side-vented irrigation needle (1 mm short of the WL), or a closed-ended plastic needle with 2 lateral outlets (TruNatomy) (1 mm short of the WL). Bacteriological samples were taken from the canals before (S1) and after preparation (S2). After another micro-CT scan, the roots were sectioned and samples were also taken from the apical canal segment (S3). Bacterial reduction was assessed by quantitative real-time polymerase chain reaction. The amount of accumulated hard tissue debris was evaluated by micro-CT. ResultsA substantial reduction in bacterial counts was observed in all 3 groups when comparing S1 with S2 (99.95%, 98.93%, and 98.90% in the open-ended, closed-ended, and TruNatomy needle groups, respectively) (P < .01). No significant differences were observed between groups for bacterial reduction in the full and apical canal (P > .05). There were no intergroup differences in the amount of accumulated hard tissue debris either (P > .05). The open-ended needle group showed significantly more specimens with quantitative real-time polymerase chain reaction negative results for bacteria in S3 than TruNatomy (P < .05). ConclusionWhen used up to an appropriate insertion depth, the 3 needle types result in similar antibacterial and cleaning performance, provided variables such as needle size and irrigant type, volume and flow rate are controlled. Exclusive analysis of the apical segment, including the isthmus, revealed that the open-ended needle yielded more cases negative for bacteria.

Throat packing via nasopharyngeal airway for severe trismus cases requiring surgical intervention under general anesthesia: A simplified and innovative approach

Throat packing is essential in oral and maxillofacial surgeries to prevent blood and tissue debris aspiration, reducing postoperative complications. Traditional oral route methods are often inadequate, especially in severe trismus cases like Oral Submucous Fibrosis (OSMF), TMJ Ankylosis, and post-traumatic conditions due to limited mouth opening. This study introduces a novel technique using a nasopharyngeal airway (NPA) for throat packing. The method involves inserting a hemostatic dressing through an NPA, ensuring minimal invasiveness and effective airway management. Proper positioning is confirmed with a laryngoscope or fiberoptic scope, and the dressing is secured to prevent dislodgement. This technique is easy, reproducible, and less injurious compared to traditional methods. At our center, throat packing via NPA was performed on 35 patients undergoing surgery under general anesthesia, resulting in high satisfaction and no reported complications.

The endocannabinoid anandamide activates pro-resolving pathways in human primary macrophages by engaging both CB2 and GPR18 receptors.

Resolution of inflammation is the cellular and molecular process that protects from widespread and uncontrolled inflammation and restores tissue function in the aftermath of acute immune events. This process is orchestrated by specialized pro-resolving mediators (SPM), a class of bioactive lipids able to reduce immune activation and promote removal of tissue debris and apoptotic cells by macrophages. Although SPMs are the lipid class that has been best studied for its role in facilitating the resolution of self-limited inflammation, a number of other lipid signals, including endocannabinoids, also exert protective immunomodulatory effects on immune cells, including macrophages. These observations suggest that endocannabinoids may also display pro-resolving actions. Interestingly, the endocannabinoid anandamide (AEA) is not only known to bind canonical type 1 and type 2 cannabinoid receptors (CB1 and CB2) but also to engage SPM-binding receptors such as GPR18. This suggests that AEA may also contribute to the governing of resolution processes. In order to interrogate this hypothesis, we investigated the ability of AEA to induce pro-resolving responses by classically-activated primary human monocyte-derived macrophages (MoDM). We found that AEA, at nanomolar concentration, enhances efferocytosis in MoDMs in a CB2- and GPR18-dependent manner. Using lipid mediator profiling, we also observed that AEA modulates SPM profiles in these cells, including levels of resolvin (Rv)D1, RvD6, maresin (MaR)2, and RvE1 in a CB2-dependent manner. AEA treatment also modulated the gene expression of SPM enzymes involved in both the formation and further metabolism of SPM such as 5-lipoxygenase and 15-Prostaglandin dehydrogenase. Our findings show, for the first time, a direct effect of AEA on the regulation of pro-resolving pathways in human macrophages. They also provide new insights into the complex interactions between different lipid pathways in activation of pro-resolving responses contributing to the reestablishment of homeostasis in the aftermath of acute inflammation.

Microglia, Trem2, and Neurodegeneration.

Microglia are a specialized type of neuroimmune cells that undergo morphological and molecular changes through multiple signaling pathways in response to pathological protein aggregates, neuronal death, tissue injury, or infections. Microglia express Trem2, which serves as a receptor for a multitude of ligands enhancing their phagocytic activity. Trem2 has emerged as a critical modulator of microglial activity, especially in many neurodegenerative disorders. Human TREM2 mutations are associated with an increased risk of developing Alzheimer disease (AD) and other neurodegenerative diseases. Trem2 plays dual roles in neuroinflammation and more specifically in disease-associated microglia. Most recent developments on the molecular mechanisms of Trem2, emphasizing its role in uptake and clearance of amyloid β (Aβ) aggregates and other tissue debris to help protect and preserve the brain, are encouraging. Although Trem2 normally stimulates defense mechanisms, its dysregulation can intensify inflammation, which poses major therapeutic challenges. Recent therapeutic approaches targeting Trem2 via agonistic antibodies and gene therapy methodologies present possible avenues for reducing the burden of neurodegenerative diseases. This review highlights the promise of Trem2 as a therapeutic target, especially for Aβ-associated AD, and calls for more mechanistic investigations to understand the context-specific role of microglial Trem2 in developing effective therapies against neurodegenerative diseases.

Biomimetic hydrogels with mesoscale collagen architecture for patient-derived tumor organoids culture

Patient-derived tumor organoids (PDTOs) shows great potential as a preclinical model. However, the current methods for establishing PDTOs primarily focus on modulating local properties, such as sub-micrometer topographies. Nevertheless, they neglect to capture the global millimeter or intermediate mesoscale architecture that have been demonstrated to influence tumor response to therapeutic treatment and tumor progression. In this study, we present a rapid technique for generating collagen bundles with an average length of 90 ± 27 μm and a mean diameter of 5 ± 1.5 μm from tumor tissue debris that underwent mechanical agitation following enzymatic digestion. The collagen bundles were subsequently utilized for the fabrication of biomimetic hydrogels, incorporating microbial transglutaminase (mTG) crosslinked gelatin. These biomimetic hydrogels, referred to as MC-gel, were specifically designed for patient-derived tumor organoids. The lung cancer organoids cultured in MC-gel exhibited larger diameters and higher cell viability compared to those cultured in gels lacking the mesoscale collagen bundle; moreover, their irregular morphology more closely resembled that observed in vivo. The MC-gel-based lung cancer organoids effectively replicated the histology and mutational landscapes observed in the original donor patient’s tumor tissue. Additionally, these lung cancer organoids showed a remarkable similarity in their gene expression and drug response across different matrices. This recently developed model holds great potential for investigating the occurrence, progression, metastasis, and management of tumors, thereby offering opportunities for personalized medicine and customized treatment options.

Arthroscopic Decompression of Calcific Tendinitis of the Shoulder and Repair of Residual Rotator Cuff Defect

Background: Calcific tendinitis is a common source of shoulder pain and represents pathologic deposition of calcium hydroxyapatite within rotator cuff tendon tissue, most commonly the supraspinatus tendon. Indications: Arthroscopic decompression of calcific tendinitis with possible rotator cuff repair is indicated in patients with persistent, debilitating symptoms of pain and/or dysfunction who are recalcitrant to nonoperative treatments, including corticosteroid administration, ultrasound-guided needle barbotage, and/or extracorporeal shockwave therapy. Technique Description: With the patient in a beach chair position, a standard diagnostic shoulder arthroscopy is performed to evaluate for concomitant pathologies. Within the subacromial space, a thorough bursectomy is performed and the area of calcium deposition is localized with a spinal needle. A scalpel may be used to create a small incision through the rotator cuff tendon in line with its fibers to promote egress of calcific debris. Surrounding tissue and loose debris are removed with an arthroscopic shaver. Following decompression, the rotator cuff repair is inspected, and if a bursal-sided or full-thickness tear is identified, an arthroscopic repair is performed with a construct individualized to the specific tear pattern. Results: Surgical treatment conferred greater functional improvement and comparable pain reduction to nonoperative treatments in a systematic review comprised of 27 randomized trials. While the addition of a rotator cuff repair remains controversial, combined excision of calcific tendinitis with concomitant rotator cuff repair led to greater functional outcomes and pain reduction at 2-year minimum follow-up compared with isolated decompression. Conclusion: Calcific tendinitis within the shoulder may be treated successfully with arthroscopic decompression and subsequent repair of a residual rotator cuff defect, followed by a graduated physical rehabilitation program. Patient Consent Disclosure Statement: The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication.

The role of foam cells in spinal cord injury: challenges and opportunities for intervention.

Spinal cord injury (SCI) results in a large amount of tissue cell debris in the lesion site, which interacts with various cytokines, including inflammatory factors, and the intrinsic glial environment of the central nervous system (CNS) to form an inhibitory microenvironment that impedes nerve regeneration. The efficient clearance of tissue debris is crucial for the resolution of the inhibitory microenvironment after SCI. Macrophages are the main cells responsible for tissue debris removal after SCI. However, the high lipid content in tissue debris and the dysregulation of lipid metabolism within macrophages lead to their transformation into foamy macrophages during the phagocytic process. This phenotypic shift is associated with a further pro-inflammatory polarization that may aggravate neurological deterioration and hamper nerve repair. In this review, we summarize the phenotype and metabolism of macrophages under inflammatory conditions, as well as the mechanisms and consequences of foam cell formation after SCI. Moreover, we discuss two strategies for foam cell modulation and several potential therapeutic targets that may enhance the treatment of SCI.

Sudden detection of pyriform sinus carcinoma during endoscopic retrograde cholangiopancreatography.

Iatrogenic trauma and perforation are among the most concerning complications of endoscopic retrograde cholangiopancreatography (ERCP). A 76-year-old man presented for management of obstructive jaundice caused by pancreatic cancer. The ERCP was planned for further evaluation of pancreatic cancer and endoscopic biliary drainage. The ERCP scope could not pass because of resistance during the initial attempt to insert it through the pyriform sinus. After two attempts, mild bleeding occurred in the oral cavity, and the ERCP scope was successfully inserted in the esophagus. Tissue debris was observed in the esophagus; however, it was considered attributable to damage during insertion. Because passage was difficult, we placed a guidewire deep in the duodenum to ensure an accurate route and removed the ERCP scope. Then, we switched to direct-view esophagogastroduodenoscopy (EGD) and observed the pyriform sinus. EGD showed an irregular ridge and stenosis, which were determined to comprise a pyriform sinus tumor. Tissue fragments at the ERCP insertion site were retrieved for pathological examination. The ERCP scope was inserted using a guidewire, and biliary drainage was completed. When unexpected resistance is noticed, endoscopic manipulation should be stopped, and a detailed evaluation should be conducted. Endoscopists, particularly trainees with limited procedural experience, should be vigilant of these potential complications.

Root canal curvature influences uncontrolled removal of dentin and cleaning efficacy after ultrasonic activation.

This study evaluated the correlation between root canal curvature and the effects of ultrasonic irrigation in the following parameters: volume of uncontrolled dentin removal (UDRVol), maximum depth of dentin defects, removal of accumulated hard tissue debris (AHTD), and canal transportation in prepared curved root canals. Twenty-four human permanent mandibular molars were divided into two groups according to root canal curvature: moderate curvature (MC: mean 25°); and severe curvature (SC: mean 48°). The specimens were scanned using an X-ray microcomputed scanner (Skyscan 1172) before and after cleaning and shaping and after the final irrigation protocol with ultrasonic irrigation. There was a moderate correlation between the degree of root canal curvature and the volume of remaining AHTD (p<0.05) and between the degree of root canal curvature and maximum depth of defects due to uncontrolled removal of dentin (p<0.05). The teeth in the SC group had a greater maximum depth of defects on the dentin wall in the apical third than the teeth in the MC group (p <0.05). Both groups had a significant reduction of AHTD in all canal thirds, but the amount of remaining AHTD in the middle and apical thirds and the whole canal was significantly greater in the SC than in the MC group (p <0.05). Canal transportation was not influenced by the canal curvature in all thirds (p >0.05). This study concluded that root canal curvature affects significantly the uncontrolled removal of dentin and remaining AHTD volume after the final irrigation protocol with ultrasonic irrigation.

Unprepared areas and centralization of oval canals prepared with WaveOne Gold or XP-endo Shaper: microcomputed tomographic analyses.

To evaluate the performance of two endodontic systems in oval canals by investigating the changes in volume, unprepared areas, and centering ability of XP-endo Shaper (XPS) and WaveOne Gold (WOG) in oval canals using microcomputed tomography (micro-CT). Thirty mandibular canines were scanned before and after preparation with WOG (25/.07 and 35/.06) or XPS (30/.01) to evaluate the volume, surface area, and canal centralization at 4 mm and 10 mm from the apical foramen. Volume and surface area increased significantly after preparation with both systems (p<0.05). However, no significant difference was observed in the unprepared areas, regarding either the entire canal (26.21% for WOG and 30.10% for XPS), or the apical segment (18.82% for WOG and 14.63% for XPS) (p >0.05). Both systems maintained canal centralization, with no difference between them. XPS and WOG had similar shaping abilities in the mandibular canine, but left almost one third of the unprepared areas.

Imaging Histology Correlations of Intraretinal Fluid in Neovascular Age-Related Macular Degeneration.

Fluid presence and dynamism is central to the diagnosis and management of neovascular age-related macular degeneration. On optical coherence tomography (OCT), some hyporeflective spaces arise through vascular permeability (exudation) and others arise through degeneration (transudation). Herein we determined whether the histological appearance of fluid manifested this heterogeneity. Two eyes of a White woman in her 90s with anti-vascular endothelial growth factor treated bilateral type 3 neovascularization secondary to age-related macular degeneration were osmicated, prepared for submicrometer epoxy resin sections, and correlated to eye-tracked spectral domain OCT. Examples of intraretinal tissue fluid were sought among similarly prepared donor eyes with fibrovascular scars, in a web-based age-related macular degeneration histopathology resource. Fluid stain intensity was quantified in reference to Bruch's membrane and the empty glass slide. Exudative fluid by OCT was slightly reflective and dynamically responded to anti-vascular endothelial growth factor. On histology, this fluid stained moderately, possessed a smooth and homogenous texture, and contained blood cells and fibrin. Nonexudative fluid in degenerative cysts and in outer retinal tubulation was minimally reflective on OCT and did not respond to anti-vascular endothelial growth factor. By histology, this fluid stained lightly, possessed a finely granular texture, and contained mainly tissue debris. Quantification supported the qualitative impressions of fluid stain density. Cells containing retinal pigment epithelium organelles localized to both fluid types. High-resolution histology of osmicated tissue can distinguish between exudative and nonexudative fluid, some of which is transudative. OCT and histological features of different fluid types can inform clinical decision-making and assist in the interpretation of newly available automated fluid detection algorithms.

Intraoperative tissue sampling for histology in chronic osteomyelitis shows high neutrophil infiltration centrally and low remains in debrided presumed infection-free regions

IntroductionHistology of debrided bone tissue is a confirmatory diagnostic criterion for fracture related infection (FRI) and prosthetic joint infection (PJI). The aim of the present study was to describe the histopathology of the first and last debrided bone tissue in chronic osteomyelitis (CO) according to the international diagnostic guidelines for FRI and PJI. Methods15 patients with CO were allocated to surgical treatment using a one-stage protocol including extensive debridement. Suspected infected bone tissue eradicated early in the debridement procedure was collected as a clearly infected sample (S1). Likewise, the last eradicated bone tissue was collected as a suspected non-infected sample (S2). The samples were processed for histology. HE-stained sections were patho-morphologically examinated. Immunohistochemistry with MAC-387 antibodies towards calprotectin was used for estimation of neutrophil granulocyte (NP) score (0, 1, 2 or 3). ResultsS1 samples showed a mean NP score of 2.6 (3 is confirmatory for infection). Following debridement, the NP score was significantly (p = 0.005) reduced to a mean NP score of 1.6. The S1 samples showed a mix of fibrovascular tissue, dense fibrosis, viable bone, bone necrosis and bone debris. S2 samples contained mostly viable bone tissue, however, often small fragments of necrotic bone or bone debris were present. ConclusionThe inflammatory response of CO still exists after debridement, although the response fades from the center. Therefore, sampling of debrided bone tissue for histology must be performed initially during surgery, otherwise there is a risk for underestimation of NP infiltration. The present results might also be highly relevant for FRI and PJI.

Enhancing debris removal in curved canals: a comparative evaluation of XP-endo Finisher and Passive Ultrasonic Irrigation.

The study aimed to compare the efficacy of XP-endo Finisher and Passive Ultrasonic Irrigation (PUI) in removing hard tissue debris from curved canals. Thirty-four mandibular molars with Vertucci's type II mesial canals were scanned in microcomputed tomography before and after preparation with HyFlex EDM, and accumulated hard tissue debris was quantified. Subsequently, the teeth were randomly divided into two groups according to the supplementary procedure: PUI with the Ultra-X insert or XP-endo Finisher. After the intervention, the specimens underwent another scanning. Two separate analyses were conducted, one for the total canal and another for the isthmus area. Unpaired and paired T-tests were used for inter- and intergroup comparisons, with a significance level set at 5%. Both supplementary methods reduced the amount of debris compared to the initial volume. Remarkably, the XP-endo Finisher achieved a significantly higher percentage of debris removal (71% for the total canal and 74% for the isthmus areas) compared to PUI (41% for the total canal and 52% for the isthmus area) (P < 0.05). Both supplementary approaches reduced the amount of hard tissue debris from canal preparation, still XP-endo Finisher showed a higher reduction compared to PUI (p < 0.05). None of the supplementary methods rendered canals completely free of hard tissue debris. However, the supplementary approach with XP-endo Finisher resulted in lower levels of hard tissue debris than PUI in curved canals with isthmuses.

C-176 loaded Ce DNase nanoparticles synergistically inhibit the cGAS-STING pathway for ischemic stroke treatment.

The neuroinflammatory responses following ischemic stroke cause irreversible nerve cell death. Cell free-double strand DNA (dsDNA) segments from ischemic tissue debris are engulfed by microglia and sensed by their cyclic GMP-AMP synthase (cGAS), which triggers robust activation of the innate immune stimulator of interferon genes (STING) pathway and initiate the chronic inflammatory cascade. The decomposition of immunogenic dsDNA and inhibition of the innate immune STING are synergistic immunologic targets for ameliorating neuroinflammation. To combine the anti-inflammatory strategies of STING inhibition and dsDNA elimination, we constructed a DNase-mimetic artificial enzyme loaded with C-176. Nanoparticles are self-assembled by amphiphilic copolymers (P[CL35-b-(OEGMA20.7-co-NTAMA14.3)]), C-176, and Ce4+ which is coordinated with nitrilotriacetic acid (NTA) group to form corresponding catalytic structures. Our work developed a new nano-drug that balances the cGAS-STING axis to enhance the therapeutic impact of stroke by combining the DNase-memetic Ce4+ enzyme and STING inhibitor synergistically. In conclusion, it is a novel approach to modulating central nervus system (CNS) inflammatory signaling pathways and improving stroke prognosis.

Comparison of transseptal puncture using a dedicated RF wire versus a mechanical needle with and without electrification in an animal model.

Mechanical force to achieve transseptal puncture (TSP) using a standard needle may lead to overshooting and injury, and can potentially be avoided using a radiofrequency (RF)-powered needle or wire. Applying electrocautery to needles and guidewires as an alternative to purpose-built RF systems has been associated with safety risks, such as tissue coring and thermal damage. The commercially available AcQCross needle-dilator system (Medtronic) features a sharp open-ended needle for mechanical puncture, as well as a built-in connector to enable energy delivery for RF puncture. This investigation compares the safety and efficacy of the AcQCross needle to the dedicated VersaCross RF wire system and generator (Baylis Medical/Boston Scientific). In an ex vivo porcine model, VersaCross wire punctures were performed using 1 s, constant mode (approx. 10 W) with maximum two attempts. AcQCross punctures were performed by applying energy for 2 s using a standard electrosurgical generator at 10 W (max. five attempts), 20 W (max. two attempts), and 30 W (max. two attempts). Efficacy was assessed in terms of puncture success and a number of energy applications required for TSP. Safety was assessed quantitatively as force required for TSP, energy required to puncture, and incidence of tissue coring, as well as by qualitative assessment of puncture sites. Additional qualitative observation of tissue cores and debris were obtained from TSP performed in live swine. RF TSP was 100% successful using the VersaCross wire with 1.0 ± 0.0 attempts. When power was used with the AcQCross needle, it failed to puncture at low (10 and 20 W) power settings; TSP was achieved with 30 W of energy with 91% success using 1.53 ± 0.51 attempts (p < .05 vs. VC) with greater variability (F1,33 = 9223.5, p < .0001). Compared to RF puncture using the VersaCross system, mechanical puncture, alone, using the AcQcross needle required six times more force (8 mm additional forward device displacement) to perforate the septum. Qualitative assessment of puncture sites revealed larger defects and more tissue charring with the AcQCross needle at 30 W compared to punctures with VersaCross wire. Tissue coring with the open-ended AcQCross needle was observed in vivo and measured to occur in 57% of punctures using the ex vivo model; no coring was observed with the closed-tip VersaCross wire. The AcQCross needle frequently required higher energy of 30 W to achieve RF TSP and was associated with tissue coring and charring, which have been, previously, reported when electrifying a standard open-ended mechanical needle or guidewire. These findings may limit safety and effectiveness compared to the VersaCross system.

Piezoelectric-based bioactive zinc oxide-cellulose acetate electrospun mats for efficient wound healing: an in vitro insight.

Being a complex physiological process involving the removal of damaged tissue debris and creating a new microenvironment for host tissue regeneration, wound healing is still a major challenge for healthcare professionals. Disruption of this process can lead to tissue inflammation, pathogenic infections, and scar formation. Current wound healing treatments primarily focus on passive tissue healing, lacking active engagement in the healing process. In recent years, a new class of functional biomaterials based on piezoelectric properties has emerged, which can actively participate in the wound healing process by harnessing mechanical forces generated from body movement. Herein, we have fabricated a bioactive Cellulose Acetate (CA) electrospun nanofibrous mat incorporating zinc oxide (ZnO) and investigated its efficiency for accelerated wound healing. We have characterized the physicochemical properties of the fabricated nanofibrous mats using various assays, including SEM, FTIR, TGA, mechanical testing, degradation analysis, porosity measurement, hemolysis assay, and piezoelectric d33 coefficient measurement. Through our investigation, we discovered the tunned piezoelectric coefficient of fabricated specimens due to incorporating ZnO into the CA fibers. In vitro studies also confirmed enhanced cell adhesion, proliferation, and migration, indicating faster wound healing potential. Overall, our findings support the efficacy of piezoelectric-based ZnO-incorporated bioactive CA nanofibrous mats for efficient wound healing.