Pharmacological Modulation of Intrarenal Pressure in a Porcine Model Using a Novel Isoprenaline-Eluting Guidewire.

Introduction: Several complications of retrograde intrarenal surgery have been attributed to inadvertent increases in intrarenal pressure. We recently described the development of an innovative isoprenaline-eluting guidewire (IsoWire). The objective of this study was to investigate the impact of this IsoWire on the intrarenal pressure and evaluate its safety. Materials and Methods: This study was performed in 17 renal units using a porcine model. As controls, the intrarenal pressure, heart rate, and mean arterial pressure were measured for a duration of six minutes with a standard guidewire placed in the renal pelvis. For the experiment, the conventional guidewire was substituted with the IsoWire and the same parameters were measured. Blood samples were taken at one-minute intervals to measure plasma isoprenaline levels. This procedure was repeated on the opposite side. Results: The mean intrarenal pressure reduction was 29% (95% CI: 13%-53%). The mean isoprenaline effect time was 174 seconds. No changes in heart rate (p = .908) or mean arterial pressure (p = .749) were recorded after IsoWire insertion. Plasma isoprenaline levels were below the quantitation threshold. Isoprenaline concentrations in the plasma were below the quantification threshold. Ureteroscopy revealed no ureteral lesions. Conclusions: The IsoWire demonstrated a safe and effective reduction of intrarenal pressure. Additional research is necessary to determine whether ureteral smooth muscle relaxation generated by isoprenaline facilitates easier insertion of a ureteral access sheath, decreases the incidence of ureteral access sheath related ureteral lesions, or even encourage the practice of sheathless retrograde intrarenal surgery.

Introducing an lsoprenaline Eluting Guidewire: Report on its Design and the Results of the Dose-Determining Pilot Study.

Introduction: Retrograde intrarenal surgery (RIRS) is associated with complications, many of which are related to the intrarenal pressure (IRP). We aim to describe the design of a novel isoprenaline-eluting guidewire ("IsoWire") and present the results from the first in vitro release studies and the first animal studies showing its effect on IRP. Materials and Methods: The IsoWire comprises a Nitinol core surrounded by a stainless-steel wire wound into a tight coil. The grooves created by this coil provided a reservoir for adding a hydrogel coating into which isoprenaline, a beta-agonist, was loaded. Animal studies were performed using a porcine model. For the control, IRP, heart rate (HR), and mean arterial pressure (MAP) were measured continuously for 6 minutes with a standard guidewire in place. For the experiment, the standard hydrophilic guidewire was removed, the IsoWire was inserted into the renal pelvis, and the same parameters were measured. Results: In vitro analysis of the isoprenaline release profile showed that most (63.9 ± 5.9%) of the loaded drug mass was released in the 1st minute, and almost all of the drug was released in the first 4 minutes exponentially. Porcine studies showed a 25.1% reduction in IRP in the IsoWire that released 10 µg in the 1st minute; however, there was a marked increase in HR. The average percentage reduction in IRP was 8.95% and 21.3% in the IsoWire that released 5 and 7.5 µg of isoprenaline, respectively, with no changes in HR or MAP. Conclusions: The IsoWire, which releases 5 and 7.5 µg of isoprenaline in the 1st minute, appears to be safe and effective in reducing the IRP. Further studies are needed to establish whether the isoprenaline-induced ureteral relaxation will render easier insertion of a ureteral access sheath, reduce IRP during sheathless RIRS, or even promote the practice of sheathless RIRS.

System for Patterning Polydopamine and VAPG Peptide on Polytetrafluoroethylene and Biodegradable Polyesters for Patterned Growth of Smooth Muscle Cells In Vitro.

Biomaterial's surface functionalization for selective adhesion and patterned cell growth remains essential in developing novel implantable medical devices for regenerative medicine applications. We built and applied a 3D-printed microfluidic device to fabricate polydopamine (PDA) patterns on the surface of polytetrafluoroethylene (PTFE), poly(l-lactic acid-co-D,l-lactic acid) (PLA), and poly(lactic acid-co-glycolic acid) (PLGA). Then, we covalently attached the Val-Ala-Pro-Gly (VAPG) peptide to the created PDA pattern to promote the adhesion of the smooth muscle cells (SMCs). We proved that the fabrication of PDA patterns allows for the selective adhesion of mouse fibroblast and human SMCs to PDA-patterned surfaces after only 30 min of in vitro cultivation. After 7 days of SMC culture, we observed the proliferation of cells only along the patterns on PTFE but over the entire surface of the PLA and PLGA, regardless of patterning. This means that the presented approach is beneficial for application to materials resistant to cell adhesion and proliferation. The additional attachment of the VAPG peptide to the PDA patterns did not bring measurable benefits due to the high increase in adhesion and patterned cell proliferation by PDA itself.

Composite microgranular scaffolds with surface modifications for improved initial osteoblastic cell proliferation.

Polyester-based granular scaffolds are a potent material for tissue engineering due to their porosity, controllable pore size, and potential to be molded into various shapes. Additionally, they can be produced as composite materials, e.g., mixed with osteoconductive ß-tricalcium phosphate or hydroxyapatite. Such polymer-based composite materials often happen to be hydrophobic, which disrupts cell attachment and decreases cell growth on the scaffold, undermining its primary function. In this work, we propose the experimental comparison of three modification techniques for granular scaffolds to increase their hydrophilicity and cell attachment. Those techniques include atmospheric plasma treatment, polydopamine coating, and polynorepinephrine coating. Composite polymer/ß-tricalcium phosphate granules have been produced in a solution-induced phase separation (SIPS) process using commercially available biomedical polymers: poly(lactic acid), poly(lactic-co-glycolic acid), and polycaprolactone. We used thermal assembly to prepare cylindrical scaffolds from composite microgranules. Atmospheric plasma treatment, polydopamine coating, and polynorepinephrine coating showed similar effects on polymer composites' hydrophilic and bioactive properties. All modifications significantly increased human osteosarcoma MG-63 cell adhesion and proliferation in vitro compared to cells cultured on unmodified materials. In the case of polycaprolactone/ß-tricalcium phosphate scaffolds, modifications were the most necessary, as unmodified polycaprolactone-based material disrupted the cell attachment. Modified polylactide/ß-tricalcium phosphate scaffold supported excellent cell growth and showed ultimate compressive strength exceeding this of human trabecular bone. This suggests that all investigated modification techniques can be used interchangeably for increasing wettability and cell attachment properties of various scaffolds for medical applications, especially those with high surface and volumetric porosity, like granular scaffolds.

Study of Correlation between Structure and Shape-Memory Effect/Drug-Release Profile of Polyurethane/Hydroxyapatite Composites for Antibacterial Implants.

The effectiveness of multifunctional composites that combine a shape-memory polyurethane (PU) matrix with hydroxyapatite (HA) as a bioactive agent and antibiotics molecules results from a specific composite structure. In this study, structure-function correlations of PU-based composites consisting of 3, 5, and 10 (wt%) of HA and (5 wt%) of gentamicin sulfate (GeS) as a model drug were investigated. The performed analysis revealed that increasing HA content up to 5 wt% enhanced hydrogen-bonding interaction within the soft segments of the PU. Differential-scanning-calorimetry (DSC) analysis confirmed the semi-crystalline structure of the composites. Hydroxyapatite enhanced thermal stability was confirmed by thermogravimetric analysis (TGA), and the water contact angle evaluated hydrophilicity. The shape-recovery coefficient (Rr) measured in water, decreased from 94% for the PU to 86% for the PU/GeS sample and to 88-91% for the PU/HA/GeS composites. These values were positively correlated with hydrogen-bond interactions evaluated using the Fourier-transform-infrared (FTIR) spectroscopy. Additionally, it was found that the shape-recovery process initiates drug release. After shape recovery, the drug concentration in water was 17 µg/mL for the PU/GeS sample and 33-47 µg/mL for the PU HA GeS composites. Antibacterial properties of developed composites were confirmed by the agar-diffusion test against Escherichia coli and Staphylococcus epidermidis.

Controlled formation of highly porous polylactic acid­calcium phosphate granules with defined structure.

Synthetic bone repair materials are becoming increasingly popular in tissue engineering as a replacement for autografts and human/animal-based bone grafts. The biomedical application requires precise control over the material composition and structure, as well as over the size of granulate used for filling the bone defects, as the pore size and interconnectivity affect the regeneration process. This paper proposes a process of alloplastic and biodegradable polylactic acid/ß-tricalcium phosphate granulates preparation and its parameters described. Using solvent-induced phase separation technique, porous spheres have been obtained in various sizes and morphologies. The design of the experiment's approach generated an experimental plan for further statistical modeling using the resulting data. The statistical modeling approach to the data from conducting a designed set of experiments allowed analysis of the influence of process parameters on the properties of the resulting granules. We confirmed that the content of ß-tricalcium phosphate plays the most significant role in the size distribution of prepared granulate. The shape of the particles becomes less spherical with higher phosphate concentration in the emulsion. The proposed technique allows preparing porous granulates in the 0.2-1.8 mm diameter range, where granules' mean diameter and sphericity are tunable with polymer and phosphate concentrations. The granulate created a potentially implantable scaffold for resected bone regeneration, as cytotoxicity tests assured the material is non-cytotoxic in vitro, and human mesenchymal stem cells have been cultured on the surface of granulates. Results from cell cultures seeded on the Resomer LR 706S granulates were the most promising.

Polymerization of l-Tyrosine, l-Phenylalanine, and 2-Phenylethylamine as a Versatile Method of Surface Modification for Implantable Medical Devices.

Surface properties are crucial for medical device and implant research and applications. We present novel polycatecholamine coatings obtained by oxidative polymerization of l-tyrosine, l-phenylalanine, and 2-phenylethylamine based on mussel glue-inspired chemistry. We optimized the reaction parameters and examined the properties of coatings compared to the ones obtained from polydopamine. We produced polycatecholamine coatings on various materials used to manufacture implantable medical devices, such as polyurethane, but also hard-to-coat polydimethylsiloxane, polytetrafluoroethylene, and stainless steel. The coating process results in significant hydrophilization of the material's surface, reducing the water contact angle by about 50 to 80% for polytetrafluoroethylene and polyurethane, respectively. We showed that the thickness, roughness, and stability of the polycatecholamine coatings depend on the chemical structure of the oxidized phenylamine. In vitro experiments showed prominent hemocompatibility of our coatings and significant improvement of the adhesion and proliferation of human umbilical vein endothelial cells. The full confluence on the surface of coated polytetrafluoroethylene was achieved after 5 days of cell culture for all tested polycatecholamines, and it was maintained after 14 days. Hence, the use of polycatecholamine coatings can be a simple and versatile method of surface modification of medical devices intended for contact with blood or used in tissue engineering.

Polydopamine and gelatin coating for rapid endothelialization of vascular scaffolds.

Rapid endothelialization helps overcome the limitations of small-diameter vascular grafts. To develop biomimetic non-thrombogenic coatings supporting endothelialization, medical-grade polyurethane (PU) nanofibrous mats and tubular scaffolds with a diameter below 6 mm prepared by solution blow spinning were coated with polydopamine (PDA), or PDA and gelatin (PDA/Gel). The scaffolds were characterized by scanning electron microscopy, porosity measurement, tensile testing, wettability, Fourier Transform Infrared spectroscopy, and termogravimetric analysis, followed by the measurement of coating stability on the tubular scaffolds. The effect of coating on scaffold endothelialization and hemocompatibility was evaluated using human umbilical vein endothelial cells (HUVECs) and human platelets, showing low numbers of adhering platelets and significantly higher numbers of HUVECs on PDA- and PDA/Gel-coated mats compared to control samples. Tubular PU scaffolds and commercial ePTFE prostheses coated with PDA or PDA/Gel were colonized with HUVECs using radial magnetic cell seeding. PDA/Gel-coated samples achieved full endothelial coverage within 1-3 days post-endothelialization. Altogether, PDA and PDA/Gel coating significantly enhance the endothelialization on the flat surfaces, tubular small-diameter scaffolds, and commercial vascular prostheses. The presented approach constitutes a fast and efficient method of improving scaffold colonization with endothelial cells, expected to work equally well upon implantation.

Superhydrophilic Polyurethane/Polydopamine Nanofibrous Materials Enhancing Cell Adhesion for Application in Tissue Engineering.

The use of nanofibrous materials in the field of tissue engineering requires a fast, efficient, scalable production method and excellent wettability of the obtained materials, leading to enhanced cell adhesion. We proposed the production method of superhydrophilic nanofibrous materials in a two-step process. The process is designed to increase the wettability of resulting scaffolds and to enhance the rate of fibroblast cell adhesion. Polyurethane (PU) nanofibrous material was produced in the solution blow spinning process. Then the PU fibers surface was modified by dopamine polymerization in water solution. Two variants of the modification were examined: dopamine polymerization under atmospheric oxygen (V-I) and using sodium periodate as an oxidative agent (V-II). Hydrophobic PU materials after the treatment became highly hydrophilic, regardless of the modification variant. This effect originates from polydopamine (PDA) coating properties and nanoscale surface structures. The modification improved the mechanical properties of the materials. Materials obtained in the V-II process exhibit superior properties over those from the V-I, and require shorter modification time (less than 30 min). Modifications significantly improved fibroblasts adhesion. The cells spread after 2 h on both PDA-modified PU nanofibrous materials, which was not observed for unmodified PU. Proposed technology could be beneficial in applications like scaffolds for tissue engineering.