Tissue Reaction Research Articles

The biointegration profile of fiber-reinforced plates following tibial implantation in sheep.

Biointegrative, mineral fiber-reinforced bone fixation implants recently introduced in orthopedic surgery have expanded available treatment options for fractures and bone deformities. This new technology aims to address the disadvantages of permanent metallic implants while overcoming inherent concerns of adverse inflammatory reactions when using polymer-based orthopedic implants. The purpose of this double-arm preclinical study was to evaluate the safety, biocompatibility, and biointegration of fiber-reinforced plates, following implantation on the tibias of eight sheep. Left tibias underwent periosteal elevation, allowing for implant attachment directly onto the cortical surface; right tibia plates were implanted over intact periosteum. Microcomputed tomography and histopathology were performed at 13, 26, 52, 78, 104, and 134 weeks postimplantation. All animals were evaluated clinically at each time point, with no evidence of local adverse reactions. Histopathology demonstrated anti-inflammatory M2-like macrophages and multinucleated giant cells corresponding to implant bioabsorption, similar for both groups at each time point, and indicating expected implant biocompatibility. Inflammatory cells (i.e., eosinophils, lymphophyctes, plasma cells, and M1-like macrophages) were absent throughout the study. The bioabsorption process had started at 13 W, with the highest rate at 52-78 W. At 104 W, only residual polymer material was left (∼5% of implant area). Low amounts of mineral fibers were evident at 78 W and were absent (fully remodeled) by 104 W. At 134 W, implants at both sites were fully bioabsorbed. In conclusion, these new fiber-reinforced implants demonstrated bone remodeling and complete biointegration, with no adverse tissue response. Clinical significance: In this double-arm, 2.5-year study, a biointegrative, fiber-reinforced plate implanted on the tibias of sheep was fully absorbed within 134 weeks, with no adverse tissue reaction. Bioabsorption was similar, with or without periosteal elevation, mimicking conditions like those observed in traumatic injuries disrupting the periosteum, open reduction and internal fixation, or minimally invasive surgeries. These results demonstrate the feasibility, versatility, and safety of this new class of biointegrative bone implants. This newly developed technology avoids the complications of the removal of metal implants.

TP53 and the Ultimate Biological Optimization Steps of Curative Radiation Oncology.

The new biological interaction cross-section-based repairable-homologically repairable (RHR) damage formulation for radiation-induced cellular inactivation, repair, misrepair, and apoptosis was applied to optimize radiation therapy. This new formulation implies renewed thinking about biologically optimized radiation therapy, suggesting that most TP53 intact normal tissues are low-dose hypersensitive (LDHS) and low-dose apoptotic (LDA). This generates a fractionation window in LDHS normal tissues, indicating that the maximum dose to organs at risk should be ≤2.3 Gy/Fr, preferably of low LET. This calls for biologically optimized treatments using a few high tumor dose-intensity-modulated light ion beams, thereby avoiding secondary cancer risks and generating a real tumor cure without a caspase-3-induced accelerated tumor cell repopulation. Light ions with the lowest possible LET in normal tissues and high LET only in the tumor imply the use of the lightest ions, from lithium to boron. The high microscopic heterogeneity in the tumor will cause local microscopic cold spots; thus, in the last week of curative ion therapy, when there are few remaining viable tumor clonogens randomly spread in the target volume, the patient should preferably receive the last 10 GyE via low LET, ensuring perfect tumor coverage, a high cure probability, and a reduced risk for adverse normal tissue reactions. Interestingly, such an approach would also ensure a steeper rise in tumor cure probability and a higher complication-free cure, as the few remaining clonogens are often fairly well oxygenated, eliminating a shallower tumor response due to inherent ion beam heterogeneity. With the improved fractionation proposal, these approaches may improve the complication-free cure probability by about 10-25% or even more.

Evaluation of the biocompatibility of various self-adhesive resin cements on subcutaneous connective tissue: An in vivo study

Background: The purpose of the study was to examine the subcutaneous connective tissue reaction to three self-adhesive resin cements.
 Methods: Sixty-three polyethylene tubes were filled with three different self-adhesive resin cements (Group Z [Zirconite], Group P [Panavia SA], and Group H [High Q Bond]). Twenty-one polyethylene tubes remained empty and were used as controls (Group C). All tubes were implanted into the subcutaneous tissue of the 21 rats. Specimens from each cement type were obtained at 7, 30, and 90 days. Quantitative assessments of inflammatory cells were performed in 5 different areas of each specimen.
 Results: All animals survive during the follow-up periods except two rats. The mean values of inflammatory cells at 90 days were 14 (±1.8), 15.1 (±3.5), 96 (±12.1), 16 (±2.1) in Groups C, H, P, and Z, respectively. The thicknesses of the fibrous capsule decreased significantly with time in all groups except Group P.
 Conclusion: Biocompatibility of self-adhesive resin cements was material-dependent. High Q Bond and Zirconite exhibited satisfactory biocompatibility; however, Panavia demonstrated a moderate inflammatory response at 90 days.

Radioprotective efficacy of Astilbin in mitigating radiation-induced lung injury through inhibition of p53 acetylation.

Radiation-induced lung injury (RILI) is a common side effect in thoracic tumor patients undergoing radiotherapy. At present, there is no ideal radio-protective agent which is widely used in RILI treatment. Astilbin (AST), a bioactive flavonoid, exhibits various biological effects, including anti-inflammatory, antioxidant, and anti-fibrotic activities, which partly result from reducing oxidative stress and inflammation in various pathogenic conditions. However, the protective efficacy of AST to ameliorate RILI has not been reported. In this study, we employed network pharmacology, RNA sequencing, and experimental evaluation to reveal the effects and pharmacological mechanism of AST to treat RILI in vivo and in vitro. We observed that AST reduced radiation-induced apoptosis, DNA damage, inflammatory reactions, and the reactive oxygen species (ROS) level in human normal lung epithelial cells BEAS-2B. Further study showed that AST treatment significantly ameliorated RILI by reducing the radiation-induced pathology changes and inflammatory reaction of lung tissue in C57BL/6J mice. Mechanistically, the expression of epithelial-mesenchymal transition (EMT) markers and radiation-triggered acetylation of the p53 protein were alleviated by AST treatment. Furthermore, AST alleviated the acetylation of p53 after intervention of Trichostatin A (TSA). Our data indicate that AST can alleviate RILI by inhibiting inflammatory reactions and the EMT process through decreasing the expression of p53 acetylation. In conclusion, our study suggests that AST has great potential to be a new protective and therapeutic compound for RILI.

Using x-ray micro computed tomography to quantify intracochlear fibrosis after cochlear implantation in a Guinea pig model

Cochlear implants (CIs) allow individuals with profound hearing loss to understand speech and perceive sounds. However, not all patients obtain the full benefits that CIs can provide and the cause of this disparity is not fully understood. One possible factor for the variability in outcomes after cochlear implantation, is the development of fibrotic scar tissue around the implanted electrode. It has been hypothesised that limiting the extent of fibrosis after implantation may improve overall CI function, and longevity of the device. Currently, histology is often used to quantify the extent of intracochlear tissue growth after implantation however this method is labour intensive, time-consuming, often involves significant user bias, and causes physical distortion of the fibrosis. Therefore, this study aimed to evaluate x-ray micro computed tomography (μCT) as a method to measure the amount and distribution of fibrosis in a guinea pig model of cochlear implantation. Adult guinea pigs were implanted with an inactive electrode, and cochleae harvested eight weeks later (n = 7) and analysed using μCT, to quantify the extent of tissue reaction, followed by histological analysis to confirm that the tissue was indeed fibrotic. Cochleae harvested from an additional six animals following implantation were analysed by μCT, before and after contrast staining with osmium tetroxide (OsO4), to enhance the visualisation of soft tissues within the cochlea, including the tissue reaction. Independent analysis by two observers showed that the quantification method was robust and provided additional information on the distribution of the response within the cochlea. Histological analysis revealed that μCT visualised dense collagenous material and new bone formation but did not capture loose, areolar fibrotic tissue. Treatment with OsO4 significantly enhanced the visible tissue reaction detected using μCT. Overall, μCT is an alternative and reliable method that can be used to quantify the extent of the CI-induced intracochlear tissue response and will be a useful tool for the in vivo assessment of novel anti-fibrotic treatments.

Remineralization ability of different root canal sealers

AimsThis research was designed to contrast the biocompatibility and remineralization ability of different sealers (BioRoot, MTA-FillApex and GuttaFlow-Bioseal). MethodTwenty rabbits were used in this study, they were randomly divided into 4 groups equally depending on the observation time“3,7,14, and 28 days” post-implantation. Each rabbit was generally anesthetized,“7cm”long incision was made on the skin of the right and left sides of the ventral aspect of the mandible of each rabbit, 4 bony cavities of approximately“5mm”in depth and“2mm”in diameter (2 cavities on the left side and 2 cavities on the right side of mandible of each rabbit) were made in the cortical surface of the buccal alveolar bone. The sealers mixed depend on manufactural instructions and immediately insert into the prepared cavities (in the right side the BioRoot and MTA-FillApex were placed while on the left side, GuttaFlow-Bioseal was placed in one cavity and the other cavity was left unfilled as control).The same volume of each sealer was placed in the corresponding cavity using disposable syringes. After each observation period, the animals were sacrificed and bone biopsy from the tested area was taken and examined histologically using Olympus light microscopy at“400X”magnification. ResultsThe obtained data were analyzed through non-parametric statistical tests using SPSS software version“22”.Kruskal-Wallis test and Mann - Whitney test were utilized at“0.05”levels of significance to evaluate the results. GuttaFlow-Bioseal displayed excellent biocompatibility in comparison to other groups indicated by low inflammatory tissue reaction at all evaluation intervals. While the BioRoot group represented better osteo-conductivity although statistically not significant than GuttaFlow-Bioseal group. ConclusionBioRoot and GuttaFlow-Bioseal showed higher osteo-conductivity and biocompatibility than MTA-FillApex. However, all sealer used in this study were well tolerated by bone tissue and might accelerate bone repair.

Hernia or hernia Defect? Experimental herniology Models in Laboratory Animals

Hernias of the anterior abdominal wall remain one of the most common surgery pathologies. There is no unified approach to modeling anterior abdominal wall hernias in the world scientific community. In order to systematize the available knowledge in this field and to contribute to the formation of a unified idea of how to create a hernia model in a laboratory animal, it seems logical to study the accumulated experience of researchers in the field of experimental herniology. We found out that hernia defects generally modeled on male laboratory rats. To understand the tissue reaction to the prosthetic material a fenestration was performed in the anterior abdominal wall (including peritoneum) except for the skin and subcutaneous fat. A replacement or prosthetic material tailored to the fenestration was sutured end-to-end into the abdominal wall. We chose laboratory rats because they are easy to take care of and cheaper than larger laboratory animals.

Respiratory form of infectious rhinotracheitis: Analysis of immunomorphological reactions

The concentration of cattle in limited areas, nutritional disorders, and imbalance of micro- and macroelements contribute to suppression of natural resistance of the organism, insufficient live weight gain, leading to the growth of infectious diseases of young animals with high rates of forced slaughter and cattle mortality. The source of the causative agent of rhinotracheitis infection – Bovine alphaherpesvirus 1 hinders the development of the livestock industry, thus, it is necessary to search for possible approaches to prevent and control this infection. The purpose of the research is to determine the immunomorphological changes in the lymphoid tissue of the trachea and bronchial system, in the regional lymph nodes of the lungs and in the spleen in calves naturally affected by infectious rhinotracheitis. The experimental studies were based on the research of immunomorphological reactions in lymphoid tissue during infection of young cattle with Bovine alphaherpesvirus 1, using polymerase chain reaction, histological and immunohistochemical methods. According to the results, it was established that hyperplasia of tracheaassociated lymphoid tissue was observed in the trachea, and hyperplasia of bronchial-associated lymphoid tissue was observed in the lungs; the affected areas of the trachea and lungs were infiltrated with lymphocytes, macrophages and plasma cells. The immunomorphological reactions of regional lymph nodes demonstrate hyperplasia of B- and T-dependent zones, and in the spleen – hyperplasia of T-dependent zones of the white pulp. Thus, immunocompetent cells of lymphoid tissue associated with B- and T-dependent areas of the trachea, bronchial system of the lungs and regional lymph nodes of the lungs, and with T-dependent areas of the spleen, are directly involved in the pathogenesis of infectious rhinotracheitis of respiratory type calves. Antibacterial therapy with antibiotics destroys pathogenic and normal flora in the intestine, but they are not effective enough on viral infection, therefore, production trials of effective means of specific prophylaxis and vaccination are the primary task of veterinary medicine

Revealing the composite fretting-corrosion mechanisms of Ti6Al4V alloy against zirconia-toughened alumina ceramic in simulated body fluid

The composite fretting-corrosion damage due to combinations of radial, tangential, rotational, and other fretting causes local adverse tissue reactions and failure of artificial joints. Previous studies have mainly focused on the single fretting mode, while ignoring the coupled effects of multimode fretting. The fretting-corrosion mechanisms between the components are not yet fully understood. In this study, the tangential-radial composite fretting was realized by applying a normal alternating load to the tangential fretting. The composite fretting corrosion behavior of zirconia toughened alumina ceramic/Ti6Al4V alloy used for the head-neck interface of an artificial hip joint under simulated body fluid was investigated. The effects of displacement and alternating load amplitude were considered. The alternating load amplitude was given by the maximum normal load and minimum normal load ratio R. The results showed that the composite fretting damage mechanisms of this pair were mainly abrasion and tribocorrosion. Cracking also existed under large displacement. The effect of alternating load on fretting corrosion was found to be mainly caused by changes in the contact area and instantaneous contact state. In addition, the alternating load during the composite fretting promoted the formation of the three-body layer in the contact area. A decrease in load ratio caused fretting to change from gross to partial slip. In the case of small displacement, the load ratio had little effect on the friction work or wear scar profile. The corrosion rate of materials and the concentration of metal ions released into the solution increased as load ratio decreased. In cases of large and medium displacement, load ratio reduction increased the friction work and expanded the wear scar. The reduction in load ratio also caused the corrosion rate of the material to increase and then decrease, and the metal ion concentration decreased.

Chitosan thread in the healing of the cecal wall of rabbits (Oryctolagus cuniculus) submitted to cecorrhaphy.

The development and evaluation of synthesis materials are crucial to reducing the morbidity and magnitude of post-enterorrhaphy surgical complications. Despite the possibility of production, chitosan thread has not yet been used in enterorrhaphy, and its effects on intestinal healing have not been evaluated. Therefore, this study aimed to evaluate the effects of chitosan thread on the intestinal wall repair of rabbits submitted to cecorrhaphy. For this, 42 rabbits were allocated into two groups with 21 animals. One group was submitted to cecorrhaphy with chitosan suture thread (CG) and the other with poliglecaprone suture thread (PG). The occurrence of postoperative complications, the intensity of edema, cellular response, formation of granulation tissue, as well as the deposition and maturation of collagen fibers, and the intensity of vascular endothelial growth factor (VEGF-α) expression, were evaluated during the intestinal wall repair process. The evaluations occurred on the 5th, 15th, and 25th postoperative (PO) days. The animals did not develop peritonitis, but adherence was observed in six animals from CG and seven from PG, with no difference between groups. The polymorphonuclear infiltrate showed higher intensity and higher amount of type III collagen fibers in CG on the 15th PO day. In contrast, a lower amount of type I collagen fibers was observed in CG samples on the 25th PO day. Therefore, the chitosan thread used for cecorrhaphy in rabbits results in minimal postoperative complications, presents biocompatibility, and bioactively assists the tissue repair process of the cecal wall, inducing minimal tissue reaction, stimulating the deposition of type III collagen fibers in the proliferative phase, with sustained VEGF-α expression, but with reduced deposition of type I fibers, indicating a delay in collagen maturation.

Downregulated Adipose Tissue Expression of Browning Genes With Increased Environmental Temperatures.

Climate change and global warming have been hypothesized to influence the increased prevalence of obesity worldwide. However, the evidence is scarce. We aimed to investigate how outside temperature might affect adipose tissue physiology and metabolic traits. The expression of genes involved in thermogenesis/browning and adipogenesis were evaluated (through quantitative polymerase chain reaction) in the subcutaneous adipose tissue (SAT) from 1083 individuals recruited in 5 different regions of Spain (3 in the North and 2 in the South). Plasma biochemical variables and adiponectin (enzyme-linked immunosorbent assay) were collected through standardized protocols. Mean environmental outdoor temperatures were obtained from the National Agency of Meteorology. Univariate, multivariate, and artificial intelligence analyses (Boruta algorithm) were performed. The SAT expression of genes associated with browning (UCP1, PRDM16, and CIDEA) and ADIPOQ were significantly and negatively associated with minimum, average, and maximum temperatures. The latter temperatures were also negatively associated with the expression of genes involved in adipogenesis (FASN, SLC2A4, and PLIN1). Decreased SAT expression of UCP1 and ADIPOQ messenger RNA and circulating adiponectin were observed with increasing temperatures in all individuals as a whole and within participants with obesity in univariate, multivariate, and artificial intelligence analyses. The differences remained statistically significant in individuals without type 2 diabetes and in samples collected during winter. Decreased adipose tissue expression of genes involved in browning and adiponectin with increased environmental temperatures were observed. Given the North-South gradient of obesity prevalence in these same regions, the present observations could have implications for the relationship of the obesity pandemic with global warming.

Rosuvastatin enhances alterations caused by Toxoplasma gondii in the duodenum of mice

Infection by Toxoplasma gondii may compromise the intestinal histoarchitecture through the tissue reaction triggered by the parasite. Thus, this study evaluated whether treatment with rosuvastatin modifies duodenal changes caused by the chronic infection induced by cysts of T. gondii. For this, female Swiss mice were distributed into infected and treated group (ITG), infected group (IG), group treated with 40 mg/kg rosuvastatin (TG) and control group (CG). After 72 days of infection, the animals were euthanized, the duodenum was collected and processed for histopathological analysis. We observed an increase in immune cell infiltration in the IG, TG and ITG groups, with injury to the Brunner glands. The infection led to a reduction in collagen fibers and mast cells. Infected and treated animals showed an increase in collagen fibers, acidic mucin-producing goblet cells, intraepithelial lymphocytes and mast cells, in addition to the reduction of muscle, neutral mucin-producing and Paneth cells. While treatment with rosuvastatin alone led to increased muscle layer, proportion of neutral mucin-producing goblet cells, Paneth cells, and reduction of collagen fibers. These findings indicate that the infection and treatment caused changes in the homeostasis of the intestinal wall and treatment with rosuvastatin potentiated most parameters indicative of inflammation.

Tissue Reaction to Low-Density Polyacrylamide Gel as a Carrier for Microimplants in the Adipose Fin of Rainbow Trout.

The implantation of optical sensors is a promising method for monitoring physiological parameters of organisms in vivo. For this, suitable hydrogels are required that can provide a biocompatible interface with the organism's tissues. Amorphous hydrogel is advantageous for administration in animal organs due to its ease of injection compared to resilient analogs. In this study, we investigated the applicability of a semi-liquid 2.5% polyacrylamide hydrogel (PAAH) as a scaffold for fluorescent polyelectrolyte microcapsules (PMs) in rainbow trout. The hydrogel was injected subcutaneously into the adipose fin, which is a small, highly translucent fold of skin in salmonids that is convenient for implanting optical sensors. Using histological methods, we compared tissue organization and in vivo stability of the applied hydrogel at the injection site after administration of uncoated PMs or PMs coated with 2.5% PAAH (PMs-PAAH) for a period of 3 to 14 days. Our results showed that the introduction of PMs into the gel did not have a masking effect, as they were recognized, engulfed, and carried away by phagocytes from the injection site. However, both PMs and PMs-PAAH were found to provoke chronic inflammation at the injection site, although according to cytokine expression in the fish spleen, the irritating effect was local and did not affect the systemic immunity of the fish. Therefore, our study suggests low applicability of 2.5% polyacrylamide as a scaffold for injectable sensors within a timeframe of days.

MicroRNA-203 inhibits migration and invasion of canine tonsillar squamous cell carcinoma cells by targeting SLUG.

Squamous cell carcinoma (SCC) occurring in the tonsils (TSCC) has a poorer prognosis than SCC occurring in other regions of the oral cavity (non-tonsillar SCC [NTSCC]) because it easily metastasizes to distant organs. This study aimed to elucidate the molecular mechanisms underlying the migration and invasion of TSCC cells in vitro. This study focused on differential microRNA (miRNA) expression using microRNA microarrays and quantitative polymerase chain reaction in canine TSCC and NTSCC tissues and cell lines. A target gene of the miRNA involved in cell migration and invasion was validated by wound healing, transwell, and luciferase assays. miR-203 expression was lower in TSCC tissues than in the normal oral mucosa and NTSCC tissues. Transfection of the miR-203 mimic resulted in the downregulation of mesenchymal marker protein expression and attenuation of cell migration and invasion in TSCC cells, but not in NTSCC cells. A dual-luciferase assay revealed that miR-203 directly targeted the mesenchymal transcription factor SLUG. SLUG overexpression enhances the migration of TSCC cells. Our study indicates that the miR-203/SLUG axis may be involved in the metastatic mechanisms of TSCC.

Regulation of localized corrosion of 316L stainless steel on osteogenic differentiation of bone morrow derived mesenchymal stem cells

Localized corrosion has become a concerning issue in orthopedic implants as it is associated with peri-implant adverse tissue reactions and implant failure. Here, the pitting corrosion of 316 L stainless steels (316 L SSs) was initiated by electrochemical polarization to simulate the in vivo localized corrosion of orthopedic implants. The effect of localized corrosion on osteogenic differentiation of bone marrow derived mesenchymal stem cells (BMSCs) was systematically studied. The results suggest that pitting corrosion of 316 L SS reduced the viability, adhesion, proliferation, and osteogenic differentiation abilities of BMSCs, especially for the cells around the corrosion pits. The relatively high concentrations of metallic ions such as Cr3+ and Ni2+ released by pitting corrosion could cause cytotoxicity to the BMSCs. The inhomogeneous electrochemical environment resulted from localized corrosion could promote reactive oxygen species (ROS) generation around the corrosion pits and cause oxidative stress of BMSCs. In addition, localized corrosion could also electrochemically interact with the cells and lead to cell membrane depolarization. The depolarized cell membranes and relatively high levels of ROS mediated the degradation of the osteogenic capacity of BMSCs. This work provides new insights into corrosion-mediated cell function degeneration as well as the material-cell interactions.

UCNPs-based nanoreactors with ultraviolet radiation-induced effect for enhanced ferroptosis therapy of tumor

The limitations of light source limit the clinical application of optical therapy technology. How to improve the application efficiency of radiant light has become the focus of researchers. Here, we synthesize a kind of UCNPs@PVP-GOx-PpIX-Fe3+ (UPGPF) nanoreactors with rare earth upconversion nanoparticles (UCNPs) as the substrate for the enhancement of ferroptosis effect by the synergistic starvation/photodynamic therapies. Firstly, glucose oxidase (GOx) and Fe3+ loaded in UPGPF nanoreactors are used to directly face the problems of insufficient H2O2 level in tumor tissue and low Fenton reaction efficiency. Further, UCNPs can absorb NIR light at 980 nm and convert low-energy photons into high-energy photons, thereby cleverly generating ultraviolet (UV) radiation induction in vivo, which can produce a synergistic effect of enhancing iron death. The in vivo experimental results of breast cancer model mice show that the UPGPF nanoreactors have significant anticancer effect and good biosafety. With the help of the optical conversion characteristics of UCNPs, this kind of treatment idea of building a UV radiation-induced microplatform in the tumor microenvironment, which leads to the synergistic enhancement of iron death effect, provides a promising innovative design strategy for tumor research.

Intractable complicated course of tricuspid valve infective endocarditis due to non-compliance of treatment with clinical guidelines with a decisive role of molecular biological study in etiological diagnosis: a case report

A clinical observation of the treatment non-compliance consequences with clinical guidelines and principles of empirical therapy selection in a female patient with intravenous drug abuse, viral hepatitis C and HIV infection, with a history of a COVID-19 and the development of uncontrolled staphylococcal infective endocarditis (IE) of the tricuspid valve, complicated recurrence of early prosthetic IE is presented. Successful treatment was achieved only by a combination of tricuspid valve replacement and the appointment of etiotropic therapy for S. aureus (MSSA). The typical clinical scenario was not accompanied by the choice of adequate empirical antibiotic therapy, despite the high suspicion of association with MSSA, which determined the complicated course of IE. Only the polymerase chain reaction of the heart valve tissue played a key role in the etiological diagnosis. The use of valve tissue polymerase chain reaction in addition to traditional microbiological methods is a valuable diagnostic study.

Human Histology after Structure Preservation Cochlear Implantation via Round Window Insertion.

Current surgical techniques aim to preserve intracochlear structures during cochlear implant (CI) insertion to maintain residual cochlear function. The optimal technique to minimize damage, however, is still under debate. The aim of this study is to histologically compare insertional trauma and intracochlear tissue formation in humans with a CI implanted via different insertion techniques. One recent temporal bone from a donor who underwent implantation of a full-length CI (576°) via round window (RW) insertion was compared with nine cases implanted via cochleostomy (CO) or extended round window (ERW) approach. Insertional trauma was assessed on H&E-stained histological sections. 3D reconstructions were generated and virtually re-sectioned to measure intracochlear volumes of fibrosis and neo-ossification. The RW insertion case showed electrode translocation via the spiral ligament. 2/9 CO/ERW cases showed no insertional trauma. The total volume of the cochlea occupied by fibro-osseous tissue was 10.8% in the RW case compared with a mean of 30.6% (range 8.7%-44.8%, N = 9) in the CO/ERW cases. The difference in tissue formation in the basal 5 mm of scala tympani, however, was even more pronounced when the RW case (12.3%) was compared with the cases with a CO/ERW approach (mean of 93.8%, range 81% to 100%, N = 9). Full-length CI insertions via the RW can be minimally traumatic at the cochlear base without inducing extensive fibro-osseous tissue formation locally. The current study further supports the hypothesis that drilling of the cochleostomy with damage to the endosteum incites a local tissue reaction. 4: Case-control study Laryngoscope, 134:945-953, 2024.

Transdermal wires for improved integration in vivo

Alternative engineering approaches have led the design of implants with controlled physical features to minimize adverse effects in biological tissues. Similar efforts have focused on optimizing the design features of percutaneous VAD drivelines with the aim to prevent infection, omitting however a thorough look on the implant-skin interactions that govern local tissue reactions. Here, we utilized an integrated approach for the biophysical modification of transdermal implants and their evaluation by chronic sheep implantation in comparison to the standard of care VAD drivelines. We developed a novel method for the transfer of breath topographical features on thin wires with modular size. We examined the impact of implant's diameter, surface topography, and chemistry on macroscopic, histological, and physical markers of inflammation, fibrosis, and mechanical adhesion. All implants demonstrated infection-free performance. The fibrotic response was enhanced by the increasing diameter of implants but not influenced by their surface properties. The implants of small diameter promoted mild inflammatory responses with improved mechanical adhesion and restricted epidermal downgrowth, in both silicone and polyurethane coated transdermal wires. On the contrary, the VAD drivelines with larger diameter triggered severe inflammatory reactions with frequent epidermal downgrowth. We validated these effects by quantifying the infiltration of macrophages and the level of vascularization in the fibrotic zone, highlighting the critical role of size reduction for the benign integration of transdermal implants with skin. This insight on how the biophysical properties of implants impact local tissue reactions could enable new solutions on the transdermal transmission of power, signal, and mass in a broad range of medical devices.

Analysis of recommended thresholds for medical evaluation in cases of radionuclide intakes.

Literature presents different thresholds for evaluation intended for screening people who may need additional medical assistance in cases of radionuclide intakes. There are thresholds based on the committed effective dose (CED), as well as thresholds based on the relative biological effectiveness-weighted absorbed dose (ADT) in the bone marrow and lungs. As in some emergency exposure scenarios with radionuclide intakes the risk for stochastic effects may be low whereas the threshold for deterministic effects may be exceeded, the aim of this analysis was to evaluate and to present the most appropriated threshold for each exposure scenario of interest. The results show that even adopting CED of 100mSv as threshold for medical evaluation, it is important to screen for tissue reactions because in some scenarios the adopted threshold for deterministic effects is reached whilst the CED is below the adopted threshold value for stochastic effects.