Intraneural electrodes can be harnessed to control neural prosthetic devices in human amputees. However, in chronic implants we witness a gradual loss of device functionality and electrode isolation due to a nonspecific inflammatory response to the implanted material, called foreign body reaction (FBR). FBR may eventually lead to a fibrous encapsulation of the electrode surface. Poly(ethylene glycol) (PEG) is one of the most common low-fouling materials used to coat and protect electrode surfaces. Yet, PEG can easily undergo encapsulation and oxidative damage in long-term in vivo applications. Poly(sulfobetaine methacrylate) - poly(SBMA) - zwitterionic hydrogels may represent more promising alternatives to minimize the FBR due to their ultra-low fouling features. Here, we tested and compared the poly(SBMA) zwitterionic hydrogel coating with the PEG coating in reducing adhesion and activation of pro-inflammatory and pro-fibrotic cells to polyimide surfaces, which are early hallmarks of FBR. We aimed to coat polyimide surfaces with a hydrogel thin film and analysed the release of a model drug from the hydrogel. We performed hydrogel synthesis, mechanical characterization and biocompatibility analysis. Cell adhesion, viability and morphology of human myofibroblasts cultured on PEG- and hydrogel-coated surfaces were evaluated through confocal microscopy-based high-content analysis (HCA). Reduced activation of pro-inflammatory human macrophages cultured on hydrogels was assessed as well as the hydrogel drug release profile. Because of its high hydration, biocompatibility, low stiffness and ultra-low fouling characteristics the hydrogel enabled lower adhesion and activation of pro-inflammatory and pro-fibrotic cells vs. polystyrene controls, and showed a long-term release of the anti-fibrotic drug Everolimus. Furthermore, a polyimide surface was successfully coated with a hydrogel thin film. Our soft zwitterionic hydrogel could outperform PEG as more suitable coating material of neural electrodes for mitigating the FBR. Such poly(SBMA)-based biomaterial could also be envisioned as long-term delivery system for a sustained release of anti-inflammatory and anti-fibrotic drugs in vivo.
Invasive intraneural electrodes implanted in peripheral nerves are neural prosthetic devices that are exploied to control advanced neural-interfaced prostheses in human amputees. One of the main issues to be faced in chronic implants is represented by the gradual loss of functionality of such intraneural interfaces due to an electrical impedance increase caused by the progressive formation of a fibrotic capsule around the electrodes, which is originally due to a nonspecific inflammatory response called foreign body reaction (FBR). In this in vitro work, we tested the biocompatibility and ultra-low fouling features of the synthetic coating - poly(ethylene glycol) (PEG) - compared to the organic polymer - zwitterionic sulfated poly(sulfobetaine methacrylate) (SBMA) hydrogel - to prevent or reduce the first steps of the FBR: plasma protein adsorption and cell adhesion to the interface. Synthesis and characterization of the SBMA hydrogel was done. Preliminary biocompatibility analysis of the zwitterionic hydrogel, using hydrogel-conditioned medium, showed no cytotoxicity at all vs. control. We seeded GFP-labelled human myofibroblasts on PEG- and SBMA hydrogel-coated polyimide surfaces and evaluated their adhesion and cell viability at different time-points. Because of the high hydration, low stiffness reflecting the one of neural tissue, and ultra-low fouling characteristics of the SBMA hydrogel, this polymer showed lower myofibroblast adhesion and different cell morphology compared to adhesion controls, thereby representing a better coating than PEG for potentially mitigating the FBR. We conclude that soft SBMA hydrogels could outperform PEG coatings in vitro as more suitable dressings of intraneural electrodes. Furthermore, such SBMA-based antifouling materials can be envisioned as long-term diffusion-based delivery systems for controlled release of anti-inflammatory and anti-fibrotic drugs in vivo.
The goal of the study was to perform quality control with a commercially available navigation system when introducing PST technique at our academic department. The learning curve was assessed by the Cumulative Sum (CUSUM) test. We hypothesized that the PST process for TKA was immediately under control after its introduction when analyzed with the CUSUM technique. The first 50 TKAs implanted with the use of PST at an academic department were scheduled to enter in a prospective, observational study. All TKAs were implanted by an experienced, high volume senior consultant with high experience in knee navigation. PSTs were carefully positioned over the bone and articular surfaces to the best fit position, without any navigated information. Then the 3D femoral and tibia PSTs positioning were recorded. The surgical procedure was then completed following the routine navigated procedure with standard navigated templates. To assess the 3D positioning of each template individually and of both templates together as a surrogate of the final TKA positioning, one point was given for each item inside the target, giving a maximal femur and tibia scores of 4 points, and a maximal knee score of 8 points, when all items were fulfilled. Following dataset was used for CUSUM chart plotting: allowable slack = 0.5SD, acceptable limit score = 6 points for knee score and 2 points for femur and tibia scores. For each measurement Mx, two CUSUMs (upper and lower CUSUMs) were calculated. These sums were plotted against the rank of the observation i. A trend in the process results in a change in the slope of the CUSUM, whereas the values are expected to fluctuate around a horizontal line if the process is in control. The process was considered out of control if upper CUSUM or lower CUSUM is outside the acceptable deviation interval.INTRODUCTION
MATERIAL AND METHODS
The patient-specific templates (PST) for total knee arthroplasty (TKA) have been developed to improve accuracy of implantation, decrease operating time and decrease costs. There remains controversy about the accuracy of PST in comparison with either navigated or conventional instruments. Furthermore, the learning curve after introducing PST has not been well defined. The goal of the present study was to perform quality control with a commercially available navigation system and the CUCUM test when introducing PST technique at our academic department. The first 50 TKAs implanted with the use of PST at an academic department were scheduled to enter in a prospective, observational study. PSTs were designed to obtain a neutral coronal alignment. All TKAs were implanted by an experienced, high volume senior consultant with high experience in knee navigation. PSTs were carefully positioned over the bone and articular surfaces to the best fit position, without any navigated information. Then the 3D femoral and tibia PSTs positioning were recorded by the navigation system. The difference between expected and achieved position was calculated, and an accuracy score was calculated and plotted according to the rank of observation into a CUSUM test.INTRODUCTION
MATERIAL AND METHODS
An appropriate positioning of a total knee replacement (TKR) is a prerequisite for a good functional outcome and a prolonged survival. Navigation systems may facilitate this proper positioning. Patient specific templates have been developed to achieve at least the same accuracy than conventional instruments at a lower cost. We hypothesised that there was no learning curve at our academic department when using patient specific templates for TKR instead of the routinely used navigation system. The first 20 patients operated on for TKR at our academic department using a patient specific template entered the study. All patients had a pre-operative CT-scan planning with a dedicated software. The patient specific templates were positioned on the bone according to the best fit technique. The position of the templates was controlled at each step of the procedure by the navigation system, and eventually corrected to achieve the expected goal. The discrepancy between the initial and the final positioning was recorded. The paired difference between each set of measurement was analysed with appropriate statistical tests at a 0.05 level of significance.Introduction
Material
High-dose antibiotic-loaded acrylic cement (ALAC) is used for managing periprosthetic joint infections (PJIs). The marked increase in resistant high-virulence bacteria is drawing the attention of physicians towards alternative antimicrobial formulations to the routinely used antibiotics. To date, few studies simultaneously investigated the elution properties of a broad range of antibiotics. The aim of thepresent All the ALAC samples showed a burst release of antibiotics in the first hour, progressively decreasing overtime, and elution curves strictly adhered to a non-linear regression analysis formula. Among aminoglycosides, commonly addressed as the most appropriate antibiotics to be loaded into the bone cement, the highest elution rate was that of tobramycin. Among the glycopeptides, commonly used to treat PJIs because of the prevalence of aminoglycoside resistance, vancomycin showed better elution in comparison with teicoplanin. Clindamycin, that can be associated with aminoglycosides to prepare ALACsshowed the highest absolute and relative elutions among all the tested formulations. A noticeable elution was also detected for colistin, an antibiotic of last resort for treating multi-drug resistant bacteria. The current study demonstrates theoretical advantages in the preparation of ALAC for some antibiotics notroutinely used in the clinical setting for PJIs. The use of these antibiotics based on the infecting bacteria sensitivity may represent an useful option for physicians to eradicate PJIs.
