Implantable electrical stimulation bioreactor with liquid crystal polymer-based electrodes for enhanced bone regeneration at mandibular large defects in rabbit.

The osseous regeneration of large bone defects is still a major clinical challenge in maxillofacial and orthopedic surgery. Previous studies demonstrated that biphasic electrical stimulation (ES) stimulates bone formation; however, polyimide electrode should be removed after regeneration. This study presents an implantable electrical stimulation bioreactor with electrodes based on liquid crystal polymer (LCP), which can be permanently implanted due to excellent biocompatibility to bone tissue. The bioreactor was implanted into a critical-sized bone defect and subjected to ES for one week, where bone regeneration was evaluated four weeks after surgery using micro-CT. The effect of ES via the bioreactor was compared with a sham control group and a positive control group that received recombinant human bone morphogenetic protein (rhBMP)-2 (20 µg). New bone volume per tissue volume (BV/TV) in the ES and rhBMP-2 groups increased to 132% (p < 0.05) and 174% (p < 0.01), respectively, compared to that in the sham control group. In the histological evaluation, there was no inflammation within the bone defects and adjacent to LCP in all the groups. This study showed that the ES bioreactor with LCP electrodes could enhance bone regeneration at large bone defects, where LCP can act as a mechanically resistant outer box without inflammation. Graphical abstract To enhance bone regeneration, a bioreactor comprising collagen sponge and liquid crystal polymer-based electrode was implanted in the bone defect. Within the defect, electrical current pulses having biphasic waveform were applied from the implanted bioreactor.

CNT bundle-based thin intracochlear electrode array.

OBJECTIVE: It is known that the insertion of the intracochlear electrode is critical procedure because the damage around cochlear structures can deteriorate hearing restoration. To reduce the trauma during the electrode insertion surgery, we developed a thin and flexible intracochlear electrode array constructed with carbon nanotube (CNT) bundles. METHODS: Each CNT bundle was used for an individual electrode channel after coated with parylene C for insulation. By encapsulating eight CNT bundles with silicone elastomer, an 8-channel intracochlear electrode array was fabricated. The mechanical and electrochemical characteristics were assessed to evaluate the flexibility and feasibility of the electrode as a stimulation electrode. The functionality of the electrode was confirmed by electrically evoked auditory brainstem responses (eABR) recorded from a rat. RESULTS: The proposed electrode has a thickness of 135 µm at the apex and 395 µm at the base. It was demonstrated that the CNT bundle-based electrodes require 6-fold the lower insertion force than metal wire-based electrodes. The electrode impedance and the cathodic charge storage capacitance (CSCc) were 2.70 kΩ âˆ -20.4° at 1 kHz and - 708 mC/cm2, respectively. The eABR waves III and V were observed when stimulation current is greater than 50 µA. CONCLUSION: A thin and flexible CNT bundle-based intracochlear electrode array was successfully developed. The feasibility of the proposed electrode was shown in terms of mechanical and electrochemical characteristics. A proposed CNT bundle-based intracochlear electrode may reduce the risk of trauma during electrode insertion surgery.

The effect of systemic lipoic acid on hearing preservation after cochlear implantation via the round window approach: A guinea pig model.

The present study aimed to evaluate the effects of systemic lipoic acid on hearing preservation after cochlear implantation. Twelve Dunkin-Hartley guinea pigs were randomly divided into two groups: the control group and the lipoic acid group. Animals in the lipoic acid group received lipoic acid intraperitoneally for 4 weeks. A sterilised silicone electrode-dummy was inserted through the round window to a depth of approximately 5 mm. The hearing level was measured using auditory brainstem responses (ABRs) prior to electrode-dummy insertion, and at 4 days and 1, 2, 3 and 4 weeks after electrode-dummy insertion. The threshold shift was defined as the difference between the pre-operative threshold and each of the post-operative thresholds. The cochleae were examined histologically 4 weeks after electrode-dummy insertion. Threshold shifts changed with frequency but not time. At 2kHz, ABR threshold shifts were statistically significantly lower in the lipoic acid group than the control group. At 8, 16 and 32kHz, there was no significant difference in the ABR threshold shift between the two groups. Histologic review revealed less intracochlear fibrosis along the electrode-dummy insertion site in the lipoic acid group than in the control group. The spiral ganglion cell densities of the basal, middle and apical turns were significantly higher in the lipoic acid group compared with the control group. Therefore, systemic lipoic acid administration appears to effectively preserve hearing at low frequencies in patients undergoing cochlear implantation. These effects may be attributed to the protection of spiral ganglion cells and prevention of intracochlear fibrosis.

Novel four-sided neural probe fabricated by a thermal lamination process of polymer films.

BACKGROUND: Ideally, neural probes should have channels with a three-dimensional (3-D) configuration to record the activities of 3-D neural circuits. Many types of 3-D neural probes have been developed; however, most of them were designed as an array of multiple shanks with electrodes located along one side of the shanks. NEW METHOD: We developed a novel liquid crystal polymer (LCP)-based neural probe with four-sided electrodes. This probe has electrodes on four sides of the shank, i.e., the front, back and two sidewalls. To generate the proposed configuration of the electrodes, we used a thermal lamination process involving LCP films and laser micromachining. RESULTS: The proposed novel four-sided neural probe, was used to successfully perform in vivo multichannel neural recording in the mouse primary somatosensory cortex. COMPARISON WITH EXISTING METHOD: The multichannel neural recording showed that the proposed four-sided neural probe can record spiking activities from a more diverse neuronal population than single-sided probes. This was confirmed by a pairwise Pearson correlation coefficient (Pearson's r) analysis and a cross-correlation analysis. CONCLUSION: The developed four-sided neural probe can be used to record various signals from a complex neural network.

Fabrication and evaluation of an improved polymer-based cochlear electrode array for atraumatic insertion.

An atraumatic cochlear electrode array has become indispensable to high-performance cochlear implants such as electric acoustic stimulation (EAS), wherein the preservation of residual hearing is significant. For an atraumatic implantation, we propose and demonstrate a new improved design of a cochlear electrode array based on liquid crystal polymer (LCP), which can be fabricated by precise batch processes and a thermal lamination process, in contrast to conventional wire-based cochlear electrode arrays. Using a thin-film process of LCP-film-mounted silicon wafer and thermal press lamination, we devise a multi-layered structure with variable layers of LCP films to achieve a sufficient degree of basal rigidity and a flexible tip. A peripheral blind via and self-aligned silicone elastomer molding process can reduce the width of the array. Measuring the insertion and extraction forces in a human scala tympani model, we investigate five human temporal bone insertion trials and record electrically evoked auditory brainstem responses (EABR) acutely in a guinea pig model. The diameters of the finalized electrode arrays are 0.3 mm (tip) and 0.75 mm (base). The insertion force with a displacement of 8 mm from a round window and the maximum extraction force are 2.4 mN and 34.0 mN, respectively. The electrode arrays can be inserted from 360° to 630° without trauma at the basal turn. The EABR data confirm the efficacy of the array. A new design of LCP-based cochlear electrode array for atraumatic implantation is fabricated. Verification indicates that foretells the development of an atraumatic cochlear electrode array and clinical implant.

Advancements in fabrication process of microelectrode array for a retinal prosthesis using Liquid Crystal Polymer (LCP).

Liquid Crystal Polymer (LCP) has been considered as an alternative biomaterial for implantable biomedical devices primarily for its low moisture absorption rate compared with conventional polymers such as polyimide, parylene and silicone elastomers. A novel retinal prosthetic device based on monolithic encapsulation of LCP is being developed in which entire neural stimulation circuitries are integrated into a thin and eye-conformable structure. Micromachining techniques for fabrication of a LCP retinal electrode array have been previously reported. In this research, however, for being used as a part of the LCP-based retinal implant, we developed advanced fabrication process of LCP retinal electrode through new approaches such as electroplating and laser-machining in order to achieve higher mechanical robustness, long-term reliability and flexibility. Thickened metal tracks could contribute to higher mechanical strength as well as higher long-term reliability when combined with laser-ablation process by allowing high-pressure lamination. Laser-thinning technique could improve the flexibility of LCP electrode.