A Dual-layered Microfluidic System for Long-term Controlled In Situ Delivery of Multiple Anti-inflammatory Factors for Chronic Neural Applications.

We report the development of a microfluidic system capable of repeated infusions of anti-inflammatory factors post-implantation for use as a coating for neural probes. This system consists of a microchannel in a thin gelatin methacryloyl (GelMA)-polyethylene glycol (PEG) composite hydrogel surrounded by a porous polydimethylsiloxane (PDMS) membrane, where the hydrogel can be dried to increase the stiffness for easy insertion. Reswelling allowed us to perfuse interleukin (IL)-4 and dexamethasone (DEX) as anti-inflammatory factors through the channel with minimal burst release and significant amounts of IL-4 were observed to release for up to 96 hr post-infusion. Repeated injections of IL-4 increased the ratio of prohealing M2 versus proinflammatory M1 phenotypes of macrophages encapsulated in the hydrogel by six fold compared with a single injection, over a 2-week period. These repeated infusions also significantly downregulated the expression of inflammatory markers tumor necrosis factor (TNF)-α and IL-6 in astrocytes encapsulated in hydrogel. To demonstrate the system as a coating of neural probe for in vivo applications, we further fabricated a prototype device, where a thin dual-layered microfluidic system was integrated onto a metal probe. Such a drug delivery system could help reduce the formation of a glial scar around neural probes.

Randomized Trial Comparing the Primary Patency following Cutting Versus High-Pressure Balloon Angioplasty for Treatment of de Novo Venous Stenoses in Hemodialysis Arteriovenous Fistulae.

PURPOSE: A single-center randomized clinical trial was performed to compare postinterventional primary patency rates achieved by cutting balloon angioplasty and high-pressure balloon angioplasty in the treatment of de novo stenoses within autogenous arteriovenous (AV) fistulae for hemodialysis. MATERIALS AND METHODS: Forty-eight patients undergoing their first angioplasty were prospectively randomized to undergo angioplasty with a cutting balloon or high-pressure balloon 4-8 mm in diameter because cutting balloons larger than 8 mm are not available. Nine patients were excluded after angiography, with seven requiring balloons larger than 8 mm. In the remaining 39 patients, there were 42 stenoses in the following regions: juxtaanastomotic (38%), perianstomotic (38%), midcephalic (9%), and cephalic arch (14%). Patients in the cutting balloon group were younger (mean age difference, 9 y; P = .04), but other demographic variables were comparable (range, P = .08-.89). The mean follow-up period was 8.5 mo (range, 24 d to 32 mo). Kaplan-Meier analysis was used to compare duration of patency. Mann-Whitney rank-sum t test and χ2/Fisher exact tests were used to compare continuous and categoric variables, respectively. RESULTS: Technical success was achieved in all 39 patients. At 3, 6, and 12 months, the postinterventional primary patency rates for the cutting balloon group were 61.1% (95% confidence interval [CI], 35.75%-82.70%), 27.7% (95% CI, 9.69%-53.48%), and 11.1% (95% CI, 1.38%-34.71%), respectively, compared with 70.0% (95% CI, 45.72%-88.11%), 42.1% (95% CI, 20.25%-66.50%), and 26.3% (95% CI, 9.15%-51.20%), respectively, for the high-pressure balloon group (P < .3 at each interval). CONCLUSIONS: Compared with high-pressure balloon angioplasty, cutting balloon angioplasty does not improve postinterventional primary patency of de novo stenotic lesions in autogenous arteriovenous fistulae.

Cell response to hydroxyapatite surface topography modulated by sintering temperature.

Increased mesenchymal stem cell (MSC) activity on hydroxyapatite (HA) bone tissue engineering scaffolds will improve their viability in diffusion-based in vivo environments and is therefore highly desirable. This work focused on modulating the sintered HA surface topography with a view to increasing cell activity; this was achieved by varying the sintering temperature of the HA substrates. Cells were cultured on the substrates for periods of up to 19 days and displayed a huge variation in viability. MSC metabolic activity was measured using a resazurin sodium salt assay and revealed that surfaces sintered from 1250 to 1350°C significantly outperformed their lower temperature counterparts from day one (p ≤ 0.05). Surfaces sintered at 1300°C induced 57% more cell activity than the control at day 16. No significant activity was observed on surfaces sintered below 1200°C. It is suggested that this is due to the granular morphology produced at these temperatures providing insufficient contact area for cell attachment. In addition, we propose the average surface wavelength as a more quantitative surface descriptor than those readily found in the literature. The wavelengths of the substrates presented here were highly correlated with cell activity (R(2) = 0.9019); with a wavelength of 2.675 µm on the 1300°C surface inducing the highest cell response.

Poly(glycerol sebacate urethane)-cellulose nanocomposites with water-active shape-memory effects.

Biodegradable and biocompatible materials with shape-memory effects (SMEs) are attractive for use as minimally invasive medical devices. Nanocomposites with SMEs were prepared from biodegradable poly(glycerol sebacate urethane) (PGSU) and renewable cellulose nanocrystals (CNCs). The effects of CNC content on the structure, water absorption, and mechanical properties of the PGSU were studied. The water-responsive mechanically adaptive properties and shape-memory performance of PGSU-CNC nanocomposites were observed, which are dependent on the content of CNCs. The PGSU-CNC nanocomposite containing 23.2 vol % CNCs exhibited the best SMEs among the nanocomposites investigated, with the stable shape fixing and shape recovery ratios being 98 and 99%, respectively, attributable to the formation of a hydrophilic, yet strong, CNC network in the elastomeric matrix. In vitro degradation profiles of the nanocomposites were assessed with and without the presence of an enzyme.

Mechanical behavior of transparent nanofibrillar cellulose-chitosan nanocomposite films in dry and wet conditions.

Transparent, biocompatible and biodegradable chitosan (CS) nanocomposite films reinforced with nanofibrillar cellulose (NFC) were prepared by solution casting. The effects of NFC content on the mechanical properties in dry and wet conditions were investigated. The incorporation of NFC significantly enhanced the mechanical properties, especially in wet conditions. The ultimate tensile strength and Young׳s modulus of chitosan were improved by 12 times and 30 times, respectively, for the nanocomposite containing 32wt% of NFC in wet conditions. The mechanism of the remarkable reinforcements was studied by analyzing the swelling behavior of NFC-CS nanocomposites. The mechanical properties of wet NFC-CS nanocomposite films matched well with those of human skin, which demonstrate potential for uses as artificial skin and wound dressings.

Endoluminal dilation technique to remove "stuck" tunneled hemodialysis catheters.

Most tunneled catheters can be easily removed after the retention cuff is dissected. Occasionally, these catheters can become resistant to removal even after application of potentially hazardous forceful traction. In addition, an infected catheter may cause life-threatening septicemia. Several methods have been described for their extraction, some of which may be available only in tertiary-care facilities. The present report describes the successful extraction of five such "stuck" catheters by using a recently described technique of endoluminal dilation. The technique appears safe and straightforward and can be performed in any interventional suite while allowing preservation of venous access.

Maintaining cell depth viability: on the efficacy of a trimodal scaffold pore architecture and dynamic rotational culturing.

Tissue-engineering scaffold-based strategies have suffered from limited cell depth viability when cultured in vitro with viable cells typically existing at the fluid-scaffold interface. This is primarily believed to be due to the lack of nutrient delivery into and waste removal from the inner regions of the scaffold construct. This work focused on the assessment of a hydroxyapatite multi-domain porous scaffold architecture (i.e. a scaffold providing a discrete domain for cell occupancy and a separate domain for nutrient delivery). It has been demonstrated that incorporating unidirectional channels into a porous scaffold material significantly enhanced initial cell seeding distribution, while maintaining relatively high seeding efficiencies. In vitro static culturing showed that providing a discrete domain for nutrient diffusion and metabolic waste removal is insufficient to enhance or maintain homogeneous cell viability throughout the entire scaffold depth during a 7-day culture period. In contrast, scaffolds subjected to dynamic rotational culturing maintained uniform cell viability throughout the scaffold depth with increasing culturing time and enhanced the extent of cell proliferation (approximately 2-2.4-fold increase) compared to static culturing.

Fabrication and characterization of a porous multidomain hydroxyapatite scaffold for bone tissue engineering investigations.

Tissue-engineering scaffold-based strategies have suffered from limited cell depth viability when cultured in vitro, with viable cells existing within the outer periphery of the fluid-scaffold interface. This is primarily believed to be due to the lack of nutrient delivery into and waste removal from the inner regions of the scaffold construct. This work develops a hydroxyapatite trimodal porous scaffold architecture (i.e., a scaffold providing a discrete domain for cell occupancy and a separate domain for nutrient delivery) through a freeze drying process. Unidirectional channels (500 microm diameter) were incorporated through CNC machining with total combined apparent porosities of 85.1% +/- 0.22%. Effective diffusion coefficients for the bimodal phase (consisting of micro- and meso-pores, without channels) were also determined (7.9 x 10(-10) m(2) s(-1)). Trimodal scaffolds also demonstrated enhanced permeability values (approximately 18-fold increase) compared with bimodal scaffold architectures. In vitro experiments were used to assess initial seeding efficiency and distribution as well as cell viability. The presence of unidirectional channels significantly enhanced initial cell seeding distribution throughout the scaffold depth, while maintaining relatively high seeding efficiencies (67.7% +/- 2.2% for trimodal, 79.1% +/- 2.1% for bimodal scaffolds). Numerical models demonstrated the effectiveness and efficacy of incorporating channels to increase the core oxygen concentration, with the accuracy of these models improved by using experimentally measured cellular oxygen consumption rates and effective diffusion coefficients. The presence of channels had a positive influence in minimizing the concentration gradients compared with bimodal scaffolds for the same cell density distributions.

Significant caval penetration by the celect inferior vena cava filter: attributable to filter design?

This report describes transmural penetration of the inferior vena cava (IVC) by a newly introduced IVC filter within 9 days of its placement. A computed tomographic study demonstrated filter penetration with one of the primary struts lodging in the uncinate process of the pancreas. Because of the close resemblance of this new filter to another filter that has not been associated with penetration injuries, the key differences between the two designs were examined and the determination was made that the new filter, unlike the older one, has unprotected primary struts. Only filters with an unprotected primary strut design have been associated with penetration injuries such as the one described in this case.

Palliation of malignant bowel obstruction using a percutaneous cecostomy.

Bowel obstruction is a common complication of metastatic gastrointestinal and ovarian cancers, and can cause distressing symptoms. Along with medical options, surgical options should be considered in all patients with bowel obstruction, including percutaneous gastrostomy. We report the case of a patient with metastatic colon cancer with an obstructing recurrence at the primary site who was not eligible for major surgery or percutaneous gastrostomy and was managed with a percutaneous cecostomy for symptom control.

Interventional procedures in whole organ and islet cell pancreas transplantation.

Pancreas organ transplantation has been a therapeutic option for the treatment of diabetes mellitus for over a decade. More recently, percutaneous injection of isolated pancreas islet cells via the portal vein has been developed as an exciting minimally invasive alternative procedure to whole organ transplantation, and one where the interventional radiologist may play a major role. This chapter reviews the role of image guided intervention in the whole organ pancreas transplant and describes the evolving technique of percutaneous islet cell transplantation.

Percutaneous transhepatic pancreatic islet cell transplantation in type 1 diabetes mellitus: radiologic aspects.

PURPOSE: To report our experience with percutaneous transhepatic pancreatic islet cell transplantation in patients with type 1 diabetes mellitus. MATERIALS AND METHODS: Between March 1999 and May 2002, 34 patients underwent 68 islet cell transplantation procedures. Patients with C-peptide-negative type 1 diabetes were selected on the basis of poor metabolic control (hypoglycemia or lability) despite compliance with optimal medical therapy. Islet cells were isolated from brain-dead donors. Access to the portal vein was gained from a right percutaneous transhepatic approach, and islet cells were infused with intermittent pressure monitoring. Twenty patients underwent two transplantations, seven patients underwent three transplantations, and seven patients underwent one transplantation. Complications during and after the procedure and postprocedural diabetic status were monitored. RESULTS: Successful portal vein cannulation and islet cell infusion were achieved in all cases. Fluoroscopy was used as the primary guidance modality in 58 of 68 (85%) procedures, and ultrasonography was used in 10 of 68 (15%). Total recorded fluoroscopy time varied from 0.6 to 103 minutes, with a median of 6.9 minutes. Potentially serious complications occurred in six of 68 (9%) procedures. Two patients developed portal venous thrombosis, and with subsequent anticoagulation therapy, one of the two developed an expanding hepatic hematoma that required surgery. Clinically important hemorrhage occurred in four patients, three of whom required blood transfusions. Of 26 patients who received completed transplants, all became insulin independent, and 81% (21 of 26) remained insulin free at 1 year. CONCLUSION: The percutaneous transhepatic approach for the implantation of islet cells into the portal vein is a safe procedure, and together with use of current cell separation techniques and an immunosuppressive regimen, offers a marked advance in the treatment of type 1 diabetes mellitus.

Portal venous pressure changes after sequential clinical islet transplantation.

BACKGROUND: Sequential pancreatic islet transplantation via the portal vein has led to insulin independence in patients with type 1 diabetes. Complications associated with the injection of islets into the portal vein have been reported; therefore, in this study we sought to further characterize changes in portal venous pressure associated with islet infusion. METHODS: Pre- and posttransplant portal venous pressures were recorded in 50 consecutive transplant procedures in 26 patients receiving highly purified, heparinized allogeneic islet preparations via a radiologically placed portal venous cannula. Doppler ultrasound scans of the portal vein were completed within 24 hr of transplantation. RESULTS: Posttransplant portal vein pressures rose significantly with sequential transplantation (12.4 mm Hg vs. 17.3 mm Hg, P <0.05). Portal pressure change correlated significantly with islet packed cell volume (r =0.66, P <0.001) and also with the number of islets transplanted ( r=0.49, P <0.001). Segmental portal vein thrombosis was radiologically detected after two procedures (4%). CONCLUSION: Multiple sequential islet transplants can be safely performed via the portal vein, provided that care is taken with islet purification and attention is paid to portal venous monitoring.