Interstitial Injection Research Articles

Electrically active defects induced by thermal oxidation and post-oxidation annealing of n-type 4H-SiC

In this work, we have performed a detailed study of the defects created in the bulk of 4H-SiC after thermal oxidation and post oxidation annealing using deep level transient spectroscopy and minority carrier transient spectroscopy (MCTS). The study reveals the formation of several shallow and deep level majority carrier traps in the bandgap. The ON1 (EC−0.85 eV), ON2a (EC−1.05 eV), and ON2b (Ec−1.17 eV) levels are the most dominant and are observed across all the samples (EC denotes the conduction band edge). Three shallow levels Ti(k) (EC−0.17 eV), E0.23 (EC−0.23 eV), and C1/2 (EC−0.36/0.39 eV) are observed in the samples. For most of the majority carrier defects, the highest concentration is observed after an NO anneal at 1300°C. This behavior is sustained in the depth profile measurements where the defect concentration after the NO anneal at 1300°C is significantly higher than for the rest of the samples. The origin of most of the majority carrier defects has been attributed to C interstitial injection from the interface during thermal oxidation and annealing. MCTS measurements reveal two prominent minority carrier traps, labeled O0.17 (EV+0.17 eV) and B (EV+0.28 eV), where the concentration of O0.17 is independent of annealing parameters while the concentration of the B level increases after the NO anneal (EV denotes the valence band edge). Furthermore, the depth profiles of the defects are used to evaluate their diffusion parameters by solving the diffusion equation to fit the experimental profiles. The defect concentrations decay exponentially with depth, which evidences that the defects were created at or near the SiO2–SiC interface and migrate toward the bulk during oxidation and post-oxidation annealing.

Improved tumour delivery of iron oxide nanoparticles for magnetic hyperthermia therapy of melanoma via ultrasound guidance and 111In SPECT quantification.

Magnetic field hyperthermia relies on the intra-tumoural delivery of magnetic nanoparticles by interstitial injection, followed by their heating on exposure to a remotely-applied alternating magnetic field (AMF). This offers a potential sole or adjuvant route to treating drug-resistant tumours for which no alternatives are currently available. However, two challenges in nanoparticle delivery currently hinder the effective clinical translation of this technology: obtaining enough magnetic material within the tumour to enable sufficient heating; and doing this accurately to limit or avoid damage to surrounding healthy tissue. A further complication is the lack of established methods to non-invasively quantify nanoparticle biodistribution, which is necessary to evaluate the performance of improved delivery strategies. Here we employ 111In radiolabelling and single-photon emission computed tomography (SPECT) to non-invasively quantify distribution of a clinical grade iron-oxide-based nanoparticle in a mouse model of melanoma. We show that compared to manual injection, ultrasound guided delivery together with syringe-pump-controlled infusion improves both the nanoparticle concentration within the tumour, and the accuracy of delivery - reducing off-target peri-tumoural delivery. Following AMF heating, injected melanomas shrank significantly compared to non-injected controls, validating therapeutic efficacy. Systemic off-target delivery was quantified and extrapolated to predict off-target energy absorbance within safe limits for the main sites of background accumulation. With many nanoparticle-based therapies currently in development for cancer, this image-guided delivery strategy has wide potential impact beyond the field of magnetic hyperthermia. Future use in representative patient cohorts would also be enabled by the high clinical availability of both SPECT and ultrasound imaging.

The lymphatic bed of the oral cavity in sheep of the Edilbaev breed

The study of the lymphatic system is of interest not only for morphology, but also for physiology and pathology, since it is in the organs and tissues where the lymphatic capillaries are located that metabolism occurs. The lymphatic bed is represented by intramural vessels, regional lymph nodes of the first and second order. The aim of the study was to determine the lymph nodes and vessels involved in the lymph outflow from the lip area in sheep of the Edilbaev breed. The study was conducted at the Department of Animal Anatomy of the St. Petersburg State University of Veterinary Medicine. The material was sheep of the Edilbaevsky breed in the amount of five pieces at the age of one year. As methods, an interstitial (interstitial) injection with cotrust masses in the form of a blue mass of Gerot was used, which was prepared by rubbing 2.0 g of blue oil paint in 30.0 g of gum turpentine. The resulting mass was mixed with 15.0 g of ether and passed through a filter. Before the injection, the sheep's head was placed in warm water for several hours. The injection is carried out with a syringe with thin needles. Contrast masses were injected very slowly, gently massaging the injected area. As a result of our research, we came to the conclusion that the direction of the main lymphatic vessels of the upper lip and the edges of the nasal opening corresponds to the line drawn from the corner of the lips to the mandibular joint; the direction of the diverting lymphatic vessels of the lower lip corresponds to the direction of the free edge of the lower jaw; the main regional lymph nodes for the diverting lymphatic vessels of the lips of the sheep of the Edilbaev breed are the parotid and mandibular and, in isolated cases, the lateral pharyngeal.

Interstitial Injection of Hydrogels with High-Mechanical Conductivity Relieves Muscle Atrophy Induced by Nerve Injury.

Injectable hydrogels have been extensively used in tissue engineering where high mechanical properties are key for their functionality at sites of high physiological stress. In this study, an injectable, conductive hydrogel is developed exhibiting remarkable mechanical strength that can withstand a pressure of 500 kPa (85% deformation rate) and display good fatigue resistance, electrical conductivity, and tissue adhesion. A stable covalent cross-linked network with a slip-ring structure by threading amino β-cyclodextrin is formed onto the chain of a four-armed (polyethylene glycol) amino group, and then reacted with the four-armed (polyethylene glycol) maleimide under physiological conditions. The addition of silver nanowires enhances the hydrogel's electrical conductivity, enabling it to act as a good conductor in vivo. The hydrogel is injected into the fascial space, and the results show that the weight and muscle tone of the atrophied gastrocnemius muscle improve, subsequently alleviating muscle atrophy. Overall, this study provides a simple method for the preparation of a conductive hydrogel with high mechanical properties. In addition, the interstitial injection provides a strategy for the use of hydrogels in vivo.

Deep Level Reduction in 4H-SiC Treated by Plasma Immersion

The carbon vacancy (VC) is a lifetime-killer defect that hinders the correct functionality of 4H-SiC bipolar devices. Until now, different methods based on carbon interstitial injection, have been proposed, in order to reduce its concentration. However, if on one hand these methods effectively reduce the VC concentration in the epilayer, on the other they cannot prevent the re-generation of VC occurring during the manufacture of a p-i-n diode, e.g., p+ implantation and activation. In the following contribution, we employ PIII of B for the formation of the anode for a p-i-n diode. We show that by PIII, it is possible to simultaneously form a p+n junction with a low concentration of VC in the drift layer.

Gold nanoparticles retrogradely penetrate through testicular barriers via Sertoli-cells mediated endocytosis/exocytosis and induce immune response in mouse

Despite the rapidly growing interest in nanoparticle-mediated controllable male contraception and recovery of male fertility, novel applications of nanoparticles in these processes are limited by a knowledge gap regarding their transport and distribution in the testes. Here, we investigated the fate of gold nanoparticles in the mouse testes using two injection methods, namely, interstitial testicular injection (IT-AuNPs, AuNPs exposure in the interstitial compartment of the testes) and rete testis injection (RT-AuNPs, AuNPs exposure in the adluminal compartment of the seminiferous tubules). In this study, we used 100 nm spherical AuNPs and microinjected with 5 μL AuNPs (30 mg/mL) for the experiments. For IT-AuNP injection, we found that AuNPs could not penetrate through the Sertoli cell-mediated blood–testis barrier (BTB) of the seminiferous tubules, and no male reproductive toxicity was observed. For RT-AuNP injection, AuNPs could be retrogradely transported from the adluminal compartment to the interstitial compartment of the testes via Sertoli cell-mediated endocytosis/exocytosis, resulting in damage and the release of inflammatory cytokines in the mouse testis. Our results highlight a retrograde nanoparticle transport function of Sertoli cells, thereby providing a mechanistic overview of the development and use of nanobiotechnology in male reproduction. SynopsisThis study provides new insights into male reproductive immunotoxicity for AuNPs exposure and elucidates a mechanism via Sertoli cell-mediated endocytosis/exocytosis.

Effects of adventitious impurity adsorption on oxygen interstitial injection rates from submerged TiO2(110) and ZnO(0001) surfaces

Low bond coordination of surface atoms facilitates the injection of oxygen interstitial atoms into the bulk near room temperature from the clean surfaces of semiconducting metal oxides when exposed to liquid water, opening new prospects for postsynthesis defect engineering and isotopic fractionation. The injection rate and penetration depth vary considerably under identical experimental conditions, however, with the adsorption of adventitious carbon suggested as the cause. For water-submerged rutile TiO2(110) and wurtzite ZnO(0001), this work bolsters and refines that hypothesis by combining the isotopic self-diffusion measurements of oxygen with characterization by x-ray photoelectron spectroscopy and atomic force microscopy. Adventitious carbon likely diminishes injection rates by poisoning small concentrations of exceptionally active surface sites that either inject O or dissociate adsorbed OH to injectable O. These effects propagate into the penetration depth via the progressive saturation of Oi traps near the surface, which occurs less extensively as the injected flux decreases.

Feasibility study of direct CT lymphangiography in mice: comparison with interstitial CT/MR lymphangiography

ObjectivesTo establish a CT lymphangiography method in mice via direct lymph node puncture.MethodsWe injected healthy mice (n = 8) with 50 µl of water-soluble iodine contrast agent (iomeprol; iodine concentration, 350 mg/mL) subcutaneously into the left-rear foot pad (interstitial injection) and 20 µl of the same contrast agent directly into the popliteal lymph node (direct puncture) 2 days later. Additionally, we performed interstitial MR lymphangiography on eight mice as a control group. We calculated the contrast ratio for each lymph node and visually assessed the depiction of lymph nodes and lymphatic vessels on a three-point scale.ResultsThe contrast ratios of 2-min post-injection images of sacral and lumbar–aortic lymph nodes were 20.7 ± 16.6 (average ± standard deviation) and 17.1 ± 12.0 in the direct puncture group, which were significantly higher than those detected in the CT or MR interstitial lymphangiography groups (average, 1.8–3.6; p = 0.008–0.019). The visual assessment scores for sacral lymph nodes, lumbar–aortic lymph nodes, and cisterna chyli were significantly better in the direct puncture group than in the CT interstitial injection group (p = 0.036, 0.009 and 0.001, respectively). The lymphatic vessels between these structures were significantly better scored in direct puncture group than in the CT or MR interstitial lymphangiography groups at 2 min after injection (all p ≤ 0.05).ConclusionsIn CT lymphangiography in mice, the direct lymph node puncture provides a better delineation of the lymphatic pathways than the CT/MR interstitial injection method.Key Points•The contrast ratios of 2-min post-injection images in the direct CT lymphangiography group were significantly higher than those of CT/MR interstitial lymphangiography groups.•The visibility of lymphatic vessels in subjective analysis in the direct CT lymphangiography group was significantly better in the direct puncture group than in the CT/MR interstitial lymphangiography groups.•CT lymphangiography with direct lymph node puncture can provide excellent lymphatic delineation with contrast being maximum at 2 min after injection.

Delayed Sentinel Lymph Node Dissection in Patients with a Preoperative Diagnosis of Ductal Cancer In Situ by Preoperative Injection with Superparamagnetic Iron Oxide (SPIO) Nanoparticles: The SentiNot Study

BackgroundDifficulty in preoperatively assessing the risk for occult invasion or surgery that precludes future accurate axillary mapping in patients with ductal cancer in situ (DCIS) account for overutilization of SLND.MethodsProspective, multicenter, cohort study, including women with any DCIS planned for mastectomy or DCIS grade 2 and > 20 mm, any DCIS grade 3, any mass-forming DCIS and any planned surgery. Patients received an interstitial SPIO injection during breast surgery, but no upfront SLND was performed. If invasion was identified on final pathology, delayed SLND (d-SLND) was performed separately with the coadministration of isotope ± blue dye (BD). Study outcomes were proportion of upfront SLNDs that were avoided, detection rates during d-SLND, and impact on healthcare costs.ResultsIn total, 78.7% of study participants (N = 254, mean age 60 years, mean DCIS size 37.8 mm) avoided upfront SLND. On d-SLND (median 28 days, range 9–46), SPIO outperformed Tc99 with (98.2% vs. 63.6%, p < 0.001) or without BD (92.7% vs. 50.9%, p < 0.001) and had higher nodal detection rate (86.9% vs. 32.3%, p < 0.001) and with BD (93.9% vs. 41.4%, p < 0.001). Only 27.9% of all SLNs retrieved were concordant for Tc99 and SPIO. Type of breast procedure (WLE vs. oncoplastic BCT vs. mastectomy) affected these outcomes and accounted for the low performance of Tc99 (p < 0.001). d-SLND resulted in a 28.1% total cost containment for women with pure DCIS on final pathology (4190 vs. 5828 USD, p < 0.001).ConclusionsMarking the SLN with SPIO may avoid overtreatment and allow for accurate d-SLND in patients with DCIS.

Identification of active spermatogenesis using a multiphoton microscope.

The sperm retrieval rate of microdissection testicular sperm extraction varies from 25% to 60%. Therefore, it is necessary to establish objective selection criteria for identifying seminiferous tubules with spermatozoa. Our aim was to develop a method for identifying spermatogenesis without sectioning testicular tissues. Testicular tissues of 10-week-old normal rats were fixed with 4% paraformaldehyde. Fluorescent labeling of seminiferous tubule nuclei and F-actin was performed, and the specimens were observed without sectioning using a multiphoton microscope. Cryptorchid rats were used as a model lacking elongated spermatids. Multiphoton images were compared with images of normal seminiferous tubules. In addition, seminiferous tubules of 10-week-old normal rats were labeled by testicular interstitial injection of fluorescent probes and observed by a multiphoton microscope without fixation. Terminal deoxynucleotidyl transferase dUTP nick end labeling-stained images of normal and probe-injected testes were compared. In fixed seminiferous tubules, elongated spermatids were identified. In addition, F-actin of apical ectoplasmic specialization was observed around elongated spermatids. Furthermore, spermatogenic stages were identified by an array of nuclei or F-actin. In cryptorchid testes, elongated spermatids and F-actin of the apical ectoplasmic specialization were not observed. In testes injected with fluorescent probes, F-actin of the apical ectoplasmic specialization was observed, and spermatogenic stages were identified without fixation. There was no significant difference in the number of terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells per seminiferous tubule between normal and probe-injected testes. Seminiferous epithelium could be observed without sectioning of tissues by fluorescent probes and a multiphoton microscope. Active spermatogenesis was observed by labeling F-actin with and without fixation. Moreover, the toxicity of fluorescent probes was limited. Our method has a potential for live imaging of testicular tissue.

Thoracic interstitial injection of drug-liposomes in mice for treating atherosclerosis

Thoracic interstitial injection of drug-liposomes in mice for treating atherosclerosis

Effects of Ultraviolet Illumination on Oxygen Interstitial Injection from TiO2 under Liquid Water

Effects of Ultraviolet Illumination on Oxygen Interstitial Injection from TiO₂ under Liquid Water

Liquid metal injected from interstitial channels for inhibiting subcutaneous hepatoma growth and improving MRI/MAT image contrast.

Liquid metal (LM) nowadays is considered a new biomedical material for medical treatment. The most common application of LM in medical therapy is taking LM as a carrier for oncology therapeutics. However, the feasibility and direct effect of LM in tumor treatment are still unknown, and how to delineate the negative resection margin (NRM) of the tumor is also a crucial problem in surgery. We aimed to inject LM into interstitial channels of extremities of mice to overlay the surface of the primary tumor to investigate the effect of LM on inhibiting tumor growth and highlight the NRM of the tumor. In this study, all 50 BALB/c-nude female mice were used to construct the transplanted HepG2-type hepatocellular carcinoma model. One week after the establishment of the model, the mice were divided into three groups, named LM group, PBS group and Control group by injecting different liquid materials into the forelimb interstitial channel of the mice. T2WI image on MRI and Magneto-acoustic tomography (MAT) were used to show the distribution of LM and PBS in vivo. The group comparisons of tumor growth and blood tests were evaluated by one-way ANOVA and post-hoc analysis. And the biocompatibility of LM to BALB/c nude mice was evaluated by histopathological analysis of LM group and control group. The volume change ratio of tumor was significantly lower in LM group than in PBS and Control group after 10 days of grouping. Compared with PBS and Control group, the main indexes of blood tests in LM group were significantly lower and close to normal level. In addition, the distribution of LM in vivo could be clearly observed under T2WI anatomic images and the crossprofile of the tumor in MAT. LM also has a obvious contrast in MRI T2WI and enhanced the amplitude of imaging signal in MAT. LM may inhibit the growth of transplanted hepatoma tumor through tumor encapsulation. In vivo, tumor imaging and LM distribution imaging were achieved by MRI T2WI, which verified that LM injected with interstitial injection made the NRM of tumor more prominent and had the potential of being MRI contrast agent. At the same time, LM could also be a new conductive medium to improve the imaging quality of MAT. Moreover, LM performed mild biocompatibility.

An engineered hydrogel with low-dose antitumor drugs enhances tumor immunotherapy through tumor interstitial wrap.

Stimulating immunogenic cell death (ICD) is the key to tumor immunotherapy. However, traditional chemoradiotherapy has limited effect on stimulating immunity and often requires repeated administration, which greatly reduces the tumor-killing effect. In this article, we created a sodium alginate hydrogel sustained-release system containing low-dose doxorubicin (Dox) and immune adjuvant R837, which were injected into the interstitial space to wrap around the tumor in situ, achieving a sustained release and long-lasting immune response. Cooperating with immune checkpoint blockade, Dox induced ICD, activated dendritic cells (DCs) and converted immunosuppressive M2-type tumor-associated macrophages (TAM) to tumor-killing M1-type TAMs. Simultaneously, it greatly promoted T cell proliferation and infiltration, and reduced tumor immunosuppressive factors, triggering a robust immune response to suppress tumors in vivo. In conclusion, this anti-tumor strategy based on interstitial injection can achieve continuous local immune stimulation by low-dose chemotherapy drugs, providing a potential approach for tumor immunotherapy.

AAV-mediated gene therapy produces fertile offspring in the Lhcgr-deficient mouse model of Leydig cell failure

Leydig cell failure (LCF) caused by gene mutation results in testosterone deficiency and infertility. Serum testosterone levels can be recovered via testosterone replacement; however, established therapies have shown limited success in restoring fertility. Here, we use a luteinizing hormone/choriogonadotrophin receptor (Lhcgr)-deficient mouse model of LCF to investigate the feasibility of gene therapy for restoring testosterone production and fertility. We screen several adeno-associated virus (AAV) serotypes and identify AAV8 as an efficient vector to drive exogenous Lhcgr expression in progenitor Leydig cells through interstitial injection. We observe considerable testosterone recovery and Leydig cell maturation after AAV8-Lhcgr treatment in pubertal Lhcgr-/- mice. Of note, this gene therapy partially recovers sexual development, substantially restores spermatogenesis, and effectively produces fertile offspring. Furthermore, these favorable effects can be reproduced in adult Lhcgr-/- mice. Our proof-of-concept experiments in the mouse model demonstrate that AAV-mediated gene therapy may represent a promising therapeutic approach for patients with LCF.

Rapamycin nanoparticles improves drug bioavailability in PLAM treatment by interstitial injection

BackgroundPulmonary lymphangiomyomatosis (PLAM) is a rare interstitial lung disease characterized by diffuse cystic changes caused by the destructive proliferation of smooth muscle-like cells or LAM cells. PLAM is more common in young women than other people, and a consensus is lacking regarding PLAM treatment. The clinical treatment of PLAM is currently dominated by rapamycin. By inhibiting the mTOR signaling pathway, rapamycin can inhibit and delay PLAM’s occurrence and development. However, the application of rapamycin also has shortcomings, including the drug’s low oral bioavailability and a high binding rate to hemoglobin, thus significantly decreasing the amount of drug distributed to the lungs.Methods and resultsHere, we developed a new mode of rapamycin administration in which the drug was injected into the intrathecal space after being nanosized; the directional flow characteristics of the liquid in the intrathecal space were exploited to increase the drug content in the interstitial fluid to the greatest extent possible. We studied the rapamycin content in the interstitial fluid and blood after intervaginal space injection (ISI). Compared with oral administration, ISI significantly increased the drug concentration in the lung interstitial fluid.ConclusionsThese results provided new ideas for treating PLAM and optimizing the dosing regimens of drugs with similar characteristics to rapamycin.

Particle-size-dependent biological distribution of gold nanoparticles after interstitial injection

There are significant differences in the biological distribution of AuNPs48 and AuNPs88 after interstitial injection, suggesting that we should consider the size effect of drugs when designing nanodrugs through interstitial injection.

Dislocation Loop Generation Differences between Thin Films and Bulk in EFDA Pure Iron under Self-Ion Irradiation at 20 MeV

In the present investigation, high-energy self-ion irradiation experiments (20 MeV Fe+4) were performed on two types of pure Fe samples to evaluate the formation of dislocation loops as a function of material volume. The choice of model material, namely EFDA pure Fe, was made to emulate experiments simulated with computational models that study defect evolution. The experimental conditions were an ion fluence of 4.25 and 8.5 × 1015 ions/cm2 and an irradiation temperature of 350 and 450 °C, respectively. First, the ions pass through the samples, which are thin films of less than 100 nm. With this procedure, the formation of the accumulated damage zone, which is the peak where the ions stop, and the injection of interstitials are prevented. As a result, the effect of two free surfaces on defect formation can be studied. In the second type of experiments, the same irradiations were performed on bulk samples to compare the creation of defects in the first 100 nm depth with the microstructure found in the whole thickness of the thin films. Apparent differences were found between the thin foil irradiation and the first 100 nm in bulk specimens in terms of dislocation loops, even with a similar primary knock-on atom (PKA) spectrum. In thin films, the most loops identified in all four experimental conditions were b ±a0&lt;100&gt;{200} type with sizes of hundreds of nm depending on the experimental conditions, similarly to bulk samples where practically no defects were detected. These important results would help validate computational simulations about the evolution of defects in alpha iron thin films irradiated with energetic ions at large doses, which would predict the dislocation nucleation and growth.

Bleomycin inhibits CLEC14A to attenuate the progression of extracranial arteriovenous malformations

BackgroundWe previously reported that interstitial injection of bleomycin (BLM) reduces the size of early-stage extracranial arteriovenous malformation (AVM). Here, we sought to investigate the potential mechanism of BLM in treating extracranial AVM. MethodsSamples of human extracranial AVM (n=3) with no pharmacological treatment were harvested. AVM endothelial cells were isolated and cultured in primary cell culture. The transcriptome was examined using RNA-sequencing, and differentially expressed C-type lectin domain family 14 member A (CLEC14A) was validated at the transcriptomic and protein levels. Immunocytochemical staining of CLEC14A was performed in samples of human extracranial AVM, with and without BLM treatment. ResultsThrough second-generation sequencing, we found that the expression of 5 689 genes were differentially increased or decreased following 24-h BLM stimulation. We found that CLEC14A may play an important role in the progression of AVM and can be inhibited by BLM treatment. ConclusionBLM inhibited CLEC14A expression to attenuate the progression of AVM.

WITHDRAWN: Intralesional interstitial injection of bleomycin for management of extracranial arteriovenous malformations in children

Despite many advances in the treatment for extracranial arteriovenous malformations (AVMs), they still result in tedious dissection and potential unacceptable complications, particularly in children. Therefore, this study aimed to investigate the efficacy and safety of intralesional interstitial injection of bleomycin for the treatment of children with AVMs. A total of 10 children (6 boys and 4 girls) with AVMs were treated with serial interstitial bleomycin injections between May 2014 and January 2017. Maximum single doses of 15 U and 1 U/kg per session were administered for six sessions at a 1-month interval. Therapeutic effectiveness was evaluated and classified into four categories: complete response (CR), partial response (PR), no response, and worsening at 3 months after the last session. Further clinical follow-up outcomes were classified as improved, stable, or aggravated. Adverse events were recorded according to the Society of Interventional Radiology classification. All 10 children completed the sessions and follow-ups. CR occurred in 3 (30%) patients, PR in 6 (60%), and no response in 1 (20%). Minor complications (class A) included maculopapular rash, bulla, vomiting, and hyperpigmentation, whereas no major complications occurred. Intralesional interstitial injection of bleomycin is a feasible approach for the treatment of AVMs in children and provides safe and effective outcomes. This method may be an earlier treatment alternative in children to prevent potential destructive progression, considering the serious complications of currently available therapeutic methods.