A Giant Stent for Giant Cerebral Aneurysms-The Accero®-Rex-Stent.

OBJECTIVE: Until now, giant intracranial aneurysms (GIAs) have in many cases been a vascular disease that was difficult or impossible to treat, not least due to the lack of availability of a large-format stent. In this multicentre study, we report on the first five clinical applications of the Accero®-Rex-Stents (Acandis, Pforzheim, Germany) in the successful treatment of fusiform cerebral giant aneurysms. MATERIAL AND METHODS: The Accero®-Rex-Stents are self-expanding, braided, fully radiopaque Nitinol stents designed for aneurysm treatment. The stent is available in three different sizes (diameter 7-10 mm, length 30-60 mm) and intended for endovascular implantation in vessels with diameters of 5.5-10 mm. RESULTS: Five patients (all male, age 54.4 ± 8.1 years) with large fusiform aneurysms of the posterior circulation were treated endovascularly using the Accero®-Rex-Stents. There were no technical complications. One major ischemic complication occurred. A significant remodeling and reduction in the size of the stent-covered aneurysms was already seen in the short-term post-interventional course. CONCLUSIONS: The Accero®-Rex-Stents were successfully and safely implanted in all five patients with fusiform giant aneurysms, showing technical feasibility with promising initial results and significant aneurysm size reduction in already available follow-up imaging. KEY POINT: With the Accero-Rex-Stents, a new device is available that offers another treatment option for rare cerebral fusiform giant aneurysms with very large parent vessels.

Management of complex thoracic aortic diseases with aberrant right subclavian artery.

BACKGROUND: We retrospectively evaluated early and intermediate outcomes of hybrid repair of complex thoracic aortic diseases involving an aberrant right subclavian artery. This paper aims to report features and available treatment options for this rare, hard-to-diagnose, and manage, aorta-related vascular condition. METHODS: Between January 2012 and May 2019, 13 patients (mean age, 60.1 ± 9.3 years; nine men) underwent complex thoracic aorta repair surgery. Six patients had a thoracic aortic aneurysm, two had type A aortic dissection, and five had complicated type B aortic dissection. Hybrid repair strategies included de-branching in combination with single-stage aortic arch replacement with the frozen elephant trunk technique performed in four patients, thoracic endovascular aortic repair in six patients, and 2-stage hybrid repair consisting of a total arch replacement with a conventional/frozen elephant trunk (first stage) and subsequent endovascular repair (second stage) in three patients. RESULTS: One early death occurred: a patient with acute type A aortic dissection, who underwent Bentall procedure and aortic arch replacement with the frozen elephant trunk technique, died in-hospital of multiorgan failure 41 days after the procedure. The remaining 12 patients were discharged in stable condition. The median follow-up duration was 36 months (2-71 months). Two late mortalities occurred: a patient with residual type A aortic dissection, who underwent arch replacement with the frozen elephant trunk technique, died of intracranial hemorrhage 3 months after the surgery. And 72 years old female patient died of acute exacerbation of chronic obstructive pulmonary disease 2 months after the surgery. CONCLUSION: Our study indicates that various hybrid strategies can be used to treat complex thoracic aortic diseases involving an aberrant right subclavian artery. The approach of choice depends on the features of disease pathology, the aortic segments involved, and the operating surgeon's experience.

Ellagic acid increases implantation rates with its antifibrotic effect in the rat model of intrauterine adhesion.

Intrauterine adhesions (IUA) are defined as the adhesion of opposing endometrial tissue with dense fibrous adhesive bands within the uterine cavity. With the increase in cesarean sections and endometrial surgical procedures, intrauterine adhesions have become a problem with increasing incidence and decreasing implantation. The purpose of the study was to investigate the effect of ellagic acid (EA), a phenolic compound, on fibrosis in IUA model rats. Another goal of the study was to increase endometrial receptivity with EA. The groups in the study were planned as control, DMSO, EA, IUA, IUA+DMSO, and IUA+EA, with 8 Sprague Dawley rats in each group. EA was administered at a dose of 100 mg/kg/day for 35 days. At the end of the experiment, the uterine tissues of the rats were removed. Histochemical staining was used to validate the IUA model and determine the degree of fibrosis. The levels of some fibrosis-related genes and proteins in the obtained uterine tissues were evaluated. In addition, implantation rates were determined. In our findings, it was observed that the fibrotic structure was decreased in the treated IUA+EA group compared to the IUA group, while fibrotic improvement was supported by down-regulation of TGFß1 activity and up-regulation of BMP7 activity. The increase in the expression of the endometrial marker LIF with EA treatment was consistent with the increase in implantation rates with treatment. As a result of the study, it can be said that EA applied as a treatment against IUA causes healing in uterine tissue by reducing fibrosis and increases implantation rates by increasing endometrial receptivity.

The effects of pharmacomechanical thrombectomy on novel complete blood count parameters in deep vein thrombosis: A retrospective study.

This study aimed to investigate the effects of pharmacomechanical thrombectomy on novel complete blood count parameters in deep venous thrombosis. This retrospective study included 242 patients aged >18 years who were treated for deep venous thrombosis. Patients were grouped as follows: group 1 was accepted as having interventional operations (n = 123) and group 2 was accepted as having only medical advice (n = 119). Routine complete blood count parameters, the neutrophil-to-lymphocyte ratio (NLR), and the platelet-to-lymphocyte ratio (PLR) were compared. There was no difference between the groups in terms of admission hemoglobin, hematocrit, mean platelet volume, NLR and PLR (P = .11, P = .24, P = .55, P = .93, and P = .96, respectively). In the pharmacomechanic thrombectomy group, NLR and PLR were significantly reduced after intervention when compared to the admission values (P < .001 and P < .001, respectively). However, the NLR and PLR values of medically treated patients did not differ significantly from their baseline values (P = .16 and P = .08, respectively). In this study, we effectively removed the thrombus load in blocked proximal veins using pharmacomechanical thrombectomy and observed a significant decrease in NLR and PLR, which are current, inexpensive, and accessible parameters.

Early results of neopulmonary valve creation technique using right atrial appendage tissue.

INTRODUCTION: Various valve repair techniques have been described for prevention of pulmonary insufficiency (PI) during right ventricular outflow tract (RVOT) reconstruction with transannular patch. Herein, we present the early results of an alternative technique of neopulmonary valve reconstruction using right atrial appendage (RAA) tissue. METHODS: Between October 2019 and December 2019, 12 patients with tetralogy of fallot (TOF) (n = 10), TOF-absent pulmonary valve (n = 1) and intact ventricular septum-pulmonary atresia (n = 1) underwent RVOT reconstruction with neopulmonary valve that was created using RAA tissue. Median age and weight of patients were 9.9 months (5 months-14 years) and 9.8 kg (6.2-47), respectively. RESULTS: No mortality or major events developed. Postoperative echocardiography revealed none/trace PI in 11 patients and mild PI in 1 patient. Median right ventricle/left ventricle ratio was 0.46 (0.35-0.65) and RVOT gradient was 20 mm Hg (0-30). Median cardiopulmonary bypass and aortic clamping times were 121 minutes (81-178) and 94 minutes (59-138), respectively. Operative times revealed statistically significant learning curve pattern in terms of cardiopulmonary bypass (r2 = .568; P = .005) and aortic clamping times (r2 = .635; P = .002). Median ventilation time, intensive care unit stay, and the length of hospital stay were 6 hours (2-48), 1 days (1-5), and 7 days (4-10), respectively. Longer perfusion time was not correlated with postoperative times. At median 6 months, echocardiography showed none/trivial PI in 11 patients and mild PI in one patient. CONCLUSION: Early results showed that neopulmonary valve reconstruction using the RAA tissue may provide a reasonable alternative for RVOT reconstruction with transannular patch. But long-term results are needed.

Short- and midterm outcomes of aortic arch reconstruction: Beating heart versus cardiac arrest.

OBJECTIVES: We aimed to compare the short- and midterm results of perfusion strategies used for arch reconstruction surgery. MATERIAL AND METHODS: One hundred and seventy-three consecutive patients who underwent aortic arch reconstruction surgery for transverse arcus hypoplasia between January 2011 and February 2020 were retrospectively analyzed. The patients were divided into two groups, as beating heart (BH) group and cardiac arrest (CA) group. RESULTS: The CA group comprised 60 (35%) patients and the remaining 113 (65%) patients were in the BH group. The median age of the patients was 30 (interquartile range: 18-95) days. The incidences of acute renal failure (ARF) and delayed sternal closure were higher in the CA group (p = .05, <.001, respectively). Balloon angioplasty was performed in 5 (2%) patients and reoperation was performed in 11 (6%) patients due to restenosis. There were no statistically significant differences between the two groups in terms of reoperation or reintervention rates (p = .44 and .34, respectively). CONCLUSIONS: Both strategies were associated with satisfactory midterm prevention of reintervention and reoperation. Given the lower incidence of ARF and delayed sternal closure in the postoperative period and similar midterm outcomes, we believe that the BH strategy is preferable.

Dual delivery of platelet-derived growth factor and bone morphogenetic factor-6 on titanium surface to enhance the early period of implant osseointegration.

OBJECTIVE: To test the surface properties and in vitro effects of a new sequential release system on MC3T3-E1 cells for improved osseointegration. BACKGROUND: BMP6-loaded anodized titanium coated with PDGF containing silk fibroin (SF) may improve osseointegration. METHODS: Titanium surfaces were electrochemically anodized, and SF layer was covered via electrospinning. Five experimental groups (unanodized Ti (Ti), anodized Ti (AnTi), anodized + BMP6-loaded Ti (AnTi-BMP6), anodized + BMP6 loaded + silk fibroin-coated Ti (AnTi-BMP6-SF), and anodized + BMP6-loaded + silk fibroin with PDGF-coated Ti (AnTi-BMP6-PDGF-SF)) were tested. After SEM characterization, contact angle analysis, and FTIR analysis, the amount of released PDGF and BMP6 was detected using ELISA. Cell proliferation (XTT), mineralization, and gene expression (RUNX2 and ALPL) were also evaluated. RESULTS: After successful anodization and loading of PDGF and BMP6, contact angle measurements showed hydrophobicity for TiO2 and hydrophilicity for protein-adsorbed surfaces. In FTIR, protein-containing surfaces exhibited amide-I, amide-II, and amide-III bands at 1600 cm-1 -1700 cm-1 , 1520 cm-1 -1540 cm-1 , and 1220 cm-1 -1300 cm-1 spectrum levels with a significant peak in BMP6- and/or SF-loaded groups at 1100 cm-1 . PDGF release and BMP6 release were delayed, and relatively slower release was detected in SF-coated surfaces. Higher MC3T3-E1 proliferation and mineralization and lower gene expression of RUNX2 and ALPL were detected in AnTi-BMP6-PDGF-SF toward day 28. CONCLUSION: The new system revealed a high potential for an improved early osseointegration period by means of a better factor release curve and contribution to the osteoblastic cell proliferation, mineralization, and associated gene expression.

A study on bone tissue engineering: Injectable chitosan-g-stearic acid putty.

BACKGROUND: Bioengineering products can help bone tissue regeneration. OBJECTIVE: There is an ongoing research for more effective biomaterials in bone regeneration. Chitosan (Ch) grafted stearic acid (Ch-g-Sa) polymer was synthesized and its usability as a putty was evaluated in this study. METHODS: The chemical structure of Ch-g-Sa polymer was investigated using Proton nuclear magnetic resonance (H-NMR) and Fourier-transformed infrared spectroscopy-attenuated total reflectance (FTIR-ATR). Thermal properties of Ch-g-Sa polymer were determined by thermal gravimetric analysis (TGA). Putties containing nano-hydroxyapatite were prepared and in-vitro degradation properties and viscosity of the putties were determined. RESULTS: The cytotoxicity, oxidation effect and osteogenic potential of the putties were investigated on MC3T3 cells while the inflammatory effect of the putties was studied on THP-1 cells. For the determination of the osteogenic effect of the putties, ALP and RUNX2 gene expression of MC3T3 cells were studied. CONCLUSION: Ch-g-Sa/HA putties are promising biomaterials for bone tissue regeneration.

Use of cyclic strain bioreactor for the upregulation of key tenocyte gene expression on Poly(glycerol-sebacate) (PGS) sheets.

The inadequate donor source and the difficulty of using natural grafts in tendon repair and regeneration has led researchers to develop biodegradable and biocompatible synthetic based tissue equivalents. Poly(glycerol sebacate) (PGS) is a surface-erodible bioelastomer and has been increasingly investigated in a variety of biomedical applications. In this study, PGS elastomeric sheets were prepared by using a facile microwave method and used as elastomeric platform for the first time under mechanical stimulation to induct the tenocyte gene expression. It is revealed that elastomeric PGS sheets promote progenitor tendon cell structure by increasing proliferation and gene expression with regard to tendon extracellular matrix components. Human tenocytes were seeded onto poly(glycerol-sebacate) sheets and were cultured two days prior to transfer to dynamic culture in a bioreactor system. Cell culture studies were carried out for 12 days under 0%, 3% and 6% strain at 0.33 Hz. The PGS-cell constructs were examined by using Scanning Electron Microscopy (SEM), cell viability via live/dead staining using confocal microscopy, and GAG/DNA analysis. In addition, gene expression was examined using real-time polymerase chain reaction (RT-PCR). Tenocytes cultured upon PGS scaffolds under 6% cyclic strain exhibited tendon-like gene expression profile compared to 3% and 0% strain groups. The results of this study show that PGS is a suitable material in promoting tendon tissue formation under dynamic conditions.

Chondrogenesis of human mesenchymal stem cells by microRNA loaded triple polysaccharide nanoparticle system.

Degenerative cartilage is the pathology of severe depletion of extracellular matrix components in articular cartilage. In diseases like osteoarthritis, misregulation of microRNAs contributes the pathology and collectively leads to disruption of the homeostasis. In this study chondroitin sulfate/hyaluronic acid/chitosan nanoparticles were prepared and successfully characterized chemically and morphologically. Results demonstrated higher chondroitin sulfate amounts led smaller nanoparticles, but lower surface zeta potential due to high electronegativity. After optimization of chondroitin sulfate amounts regarding size and charge, nanoparticles were loaded with microRNA-149-5p, a therapeutic miRNA downregulated in osteoarthritis, and evaluated focusing on their loading efficiency, release behaviour, cytotoxicity and gene transfection efficiency in vitro. Results showed all nanoparticle formulations were non-toxic and promising gene delivery agents, due to increased levels of microRNA-149-5p and decreased mRNA levels of microRNA's target, FUT-1. Highest gene transfection efficiency was obtained with the nanoparticle formulation which had the highest chondroitin sulfate load and smallest size. In addition, owing to their high chondroitin sulfate cargo, all nanoparticles were reported to enhance chondrogenesis, which was demonstrated by gene expression analysis and sulfated glycosaminoglycan (sGAG) staining. The obtained data suggest that the delivery of microRNA-149-5p via polysaccharide based carriers could achieve collaborative impact in cartilage regeneration and have a potential to enhance osteoarthritis treatment.

Preparation and characterization of novel albumin-sericin nanoparticles as siRNA delivery vehicle for laryngeal cancer treatment.

Small interfering RNA (siRNA)-based gene silencing strategy has high potential on suppressing specific molecular targets, involved in cancer progression. However, the lack of an effective nanocarrier system that safely delivers siRNA to its target still limits the clinical applications of siRNA. This study aimed to develop albumin-sericin nanoparticles (Alb-Ser NPs) as a novel siRNA delivery system for laryngeal cancer treatment. Nanoparticle formulations composed of albumin and sericin at different ratios (1:1, 2:1, 1:2 w/w) were synthesized by desolvation method. The nanoparticles were modified with poly-L-lysine (PLL) for siRNA binding and decorated with hyaluronic acid (HA) to target laryngeal cancer cell line, Hep-2. HA/PLL/Alb-Ser NPs were individually loaded with siRNAs for casein kinase 2 (CK2), Absent, Small, or Homeotic-Like (ASH2L), and Cyclin D1 genes, which are overexpressed in Hep-2 cells. Downregulation of genes was confirmed by real-time PCR (RT-PCR). Size, morphological, and thermogravimetric characterizations revealed that Alb-Ser NPs having 2:1 (w/w) ratio are the most optimized formulation. Between 36.8 and 61.3% of siRNA entrapment efficiencies were achieved. HA/PLL-siRNA/Alb-Ser (2:1) NPs-mediated gene silencing resulted in a significant inhibition of cell growth and induction of apoptosis in cells. Our findings showed that HA/PLL/Alb-Ser (2:1) NPs were promising as a siRNA carrier.

Preparation of MC3T3-E1 cell sheets through short-term osteogenic medium application.

Cell sheet engineering is an emerging field based on the acquisition of cells together with their extracellular matrix (ECM) and is used not only in vitro but also in regeneration studies of various tissues in the clinic. Within this scope, wide variety of cell types have been investigated in terms of sheet formation and underlying mechanism. MC3T3-E1 is a mouse pre-osteoblast cell line that has greatly attracted researchers' attention for bone tissue engineering (BTE) applications thanks to its high proliferation and differentiation properties. The potential of MC3T3-E1 cells on sheet formation and the effects of culture conditions have not been investigated in detail. This study aims to examine the effects of growth and osteogenic medium on cell sheet formation of MC3T3-E1. As a result of this study; intact, ECM-rich, transferable cell sheets at the beginning of the mineralization phase of the differentiation process were obtained by using osteogenic medium. Hereafter, 3D tissue model can be constructed by stacking MC3T3 cell sheets in vitro. This 3D model can conveniently be used for the development of novel biomaterials and in vitro drug screening applications to reduce the need for animal experiments.

The effect of calcium chloride concentration on alginate/Fmoc-diphenylalanine hydrogel networks.

Peptide based hydrogels gained a vast interest in the tissue engineering studies thanks to great superiorities such as biocompatibility, supramolecular organization without any need of additional crosslinker, injectability and tunable nature. Fmoc-diphenylalanine (FmocFF) is one of the earliest and widely used example of these small molecule gelators that have been utilized in biomedical studies. However, Fmoc-peptides are not feasible for long term use due to low stability and weak mechanical properties at neutral pH. In this study, Fmoc-FF dipeptides were mechanically enhanced by incorporation of alginate, a biocompatible and absorbable polysaccharide. The binary hydrogel is obtained via molecular self-assembly of FmocFF dipeptide in alginate solution followed by ionic crosslinking of alginate moieties with varying concentrations of calcium chloride. Hydrogel characterization was evaluated in terms of morphology, viscoelastic moduli and diffusional phenomena and the structures were tested as 3D scaffolds for bovine chondrocytes. In vitro evaluation of scaffolds lasted up to 14days and cell viability, sulphated glycosaminoglycan (sGAG) levels, collagen type II synthesis were determined. Our results showed that alginate incorporation into FmocFF hydrogels leads to better mechanical properties and higher stability with good biocompatibility.