Micro injection molding of individualised implants using 3D printed molds manufactured via digital light processing

Here, we demonstrate a manufacturing process for individualised, small-sized implant prototypes. Our process is promising for the manufacturing of drug-releasing (micro)implants to be implanted in the round window niche (RWN-I, solid body, free-form-shaped design, 1.1 x 2.7 x 3.1 mm) and for frontal neo-ostium implants (FO-I, tube-like design, length ~ 7 mm, Ø ~ 2-6 mm) for frontal sinus drainage. Implant prototypes are manufactured using micro injection molding (μIM). We use digital light processing (DLP) as a 3D printing technique for rapid tooling of accurate molds for the μIM process. A common acrylate-based photopolymer for stiff and high-detailed modelling but with low head deflection temperature of HDT = 60.5 °C is used for DLP 3D printing of the molds. The molds were 3D printed with a layer height of 50 μm in about 20 min (RWN-I) and 60 min (FO-I). For μIM investigations, we use liquid silicone rubber (LSR) as a biocompatible and medically relevant material. Micro injection molding of LSR was investigated using mold temperatures between Tmold = 110 °C (long tcuring ~ 2 h) up to Tmold = 160 °C (short tcuring ~ 5 min). As a result, small-sized, complex-shaped implant prototypes of LSR can be successfully manufactured via μIM using high Tmold = 160 °C and short curing time. DLP 3D printing material with relative low HDT = 60.5 °C was suitable for μIM. There is no significant wear of the molds, when used for a low number of μIM cycles (n ~ 8). Design of metal mold housing has to be suitable (perfect fit of mold, no cavities facing the molds surface for prevention of thermal expansion of mold into cavities).

Umbilical Cord Mesenchymal Stromal Cell-Derived Exosomes Rescue the Loss of Outer Hair Cells and Repair Cochlear Damage in Cisplatin-Injected Mice

Umbilical cord-derived mesenchymal stromal cells (UCMSCs) have potential applications in regenerative medicine. UCMSCs have been demonstrated to repair tissue damage in many inflammatory and degenerative diseases. We have previously shown that UCMSC exosomes reduce nerve injury-induced pain in rats. In this study, we characterized UCMSC exosomes using RNA sequencing and proteomic analyses and investigated their protective effects on cisplatin-induced hearing loss in mice. Two independent experiments were designed to investigate the protective effects on cisplatin-induced hearing loss in mice: (i) chronic intraperitoneal cisplatin administration (4 mg/kg) once per day for 5 consecutive days and intraperitoneal UCMSC exosome (1.2 μg/μL) injection at the same time point; and (ii) UCMSC exosome (1.2 μg/μL) injection through a round window niche 3 days after chronic cisplatin administration. Our data suggest that UCMSC exosomes exert protective effects in vivo. The post-traumatic administration of UCMSC exosomes significantly improved hearing loss and rescued the loss of cochlear hair cells in mice receiving chronic cisplatin injection. Neuropathological gene panel analyses further revealed the UCMSC exosomes treatment led to beneficial changes in the expression levels of many genes in the cochlear tissues of cisplatin-injected mice. In conclusion, UCMSC exosomes exerted protective effects in treating ototoxicity-induced hearing loss by promoting tissue remodeling and repair.

Determination of the Round Window Niche Anatomy Using Cone Beam Computed Tomography Imaging as Preparatory Work for Individualized Drug-Releasing Implants

Modern therapy of inner ear disorders is increasingly shifting to local drug delivery using a growing number of pharmaceuticals. Access to the inner ear is usually made via the round window membrane (RWM), located in the bony round window niche (RWN). We hypothesize that the individual shape and size of the RWN have to be taken into account for safe reliable and controlled drug delivery. Therefore, we investigated the anatomy and its variations. Cone beam computed tomography (CBCT) images of 50 patients were analyzed. Based on the reconstructed 3D volumes, individual anatomies of the RWN, RWM, and bony overhang were determined by segmentation using 3D SlicerTM with a custom build plug-in. A large individual anatomical variability of the RWN with a mean volume of 4.54 mm3 (min 2.28 mm3, max 6.64 mm3) was measured. The area of the RWM ranged from 1.30 to 4.39 mm2 (mean: 2.93 mm2). The bony overhang had a mean length of 0.56 mm (min 0.04 mm, max 1.24 mm) and the shape was individually very different. Our data suggest that there is a potential for individually designed and additively manufactured RWN implants due to large differences in the volume and shape of the RWN.

Cochlear Implantation Following Explorative Tympanotomy in Patients With Sudden Sensorineural Hearing Loss: Surgical Features and Audiological Outcomes

Objective: To investigate the anatomical status of the round window niche and hearing outcome of cochlear implantation (CI) after explorative tympanotomy (ExT) with sealing of the round window membrane in patients with sudden sensorineural hearing loss at a tertiary referral medical center. Methods: Between January 1, 2007, and July 30, 2020, 1602 patients underwent CI at our department. Out of these, all patients previously treated by ExT with sealing of the round window membrane because of unilateral sudden hearing loss were included in the study. A retrospective chart review was conducted concerning method of round window membrane sealing, intraoperative findings during CI, postoperative imaging, and hearing results. Results: Twenty one patients (9 females; 8 right ears; 54.3 years [± 12.9 years]) underwent ExT with sealing of the round window membrane with subsequent CI after 26.6 months (± 32.9 mo) on average. During CI, in 76% of cases (n = 16), the round window niche was blocked by connective tissue due to the previous intervention but could be removed completely in all cases. The connective tissue itself and its removal had no detrimental effects on the round window membrane. Postoperative computed tomography scan showed no electrode dislocation. Mean postoperative word recognition score after 3 months was 57.4% (± 17.2%) and improved significantly to 73.1% (± 16.4%, P = .005) after 2 years. Conclusion: Performing CI after preceding ExT, connective tissue has to be expected blocking the round window niche. Remaining tissue can be removed safely and does not alter the round window membrane allowing for a proper electrode insertion. Short- and long-term hearing results are satisfactory. Consequently, ExT with sealing of the round window membrane in patients with sudden sensorineural hearing loss does not impede subsequent CI that can still be performed safely.

Comparison of Round Window Anatomy between Pediatric and Adult Population: A Perspective from Cochlear Implantation Surgery

Introduction The round window is thought to be an ideal port for inserting electrodes during cochlear implantation. Considering its complex anatomy with an individual variation, this study aims to review the anatomy of round window based on the visibility of round window niche and round window membrane via posterior tympanotomy in pediatric and adult population who underwent cochlear implantation. MethodsThis was a retrospective observational study conducted at the Department of ENT-HNS, Institute of Medicine, Kathmandu, Nepal. Surgical notes of adult (>15 years) and pediatric cases (<15years) who underwent primary cochlear implantation from January 2015 to January 2018 were assessed for different grading of round window niche and round window membrane visibility via posterior tympanotomy. Cases with revision surgery and with incomplete documentation of intra-operative findings were excluded from the study. Statistical analysis was done using SPSS software version 25. We used Chi-square and Fisher’s exact tests to analyze the statistical association. ResultsType B round window niche (partially visible) was the most common variant seen in the pediatric group while in adults, both Type B (partially visible) and Type C (fully visible) round window niche were common. Compared to the adults, the pediatric group had good visibility of RWM. However, there was no statistical association between these observations. ConclusionThe round window has a wide range of anatomical variations with different levels of visibility of RWN and RWM in the different age groups. Although statistically insignificant, RWM visibility seemed to be better in pediatric cases compared to adults.

A Case of Cochlear Implantation in a Child with Congenital Aural Atresia and Cochlear and Cochlear Nerve Malformation

Congenital aural atresia (CAA) is usually accompanied by an anomalous course of facial nerves, which may run over the round window niche toward the promontory in some cases of CAA. Very rarely, cochlear malformation might coexist at the same ear which has CAA, in which case cochlear implantation can be difficult due to anomalous facial nerve. Herein we present a case of cochlear implantation performed in a child who had CAA along with cochlear hypoplasia and cochlear nerve aplasia. The mastoid segment of facial nerve was displaced anteriorly, running over the round window niche. The surgery was done successfully using the round window approach without facial nerve injury.

Endoscopic visualisation of the round window during cochlear implantation

BackgroundEndoscopes provide a magnified view of the middle ear and visualisation of hidden areas. Otoendoscopes facilitate excellent visualisation of the round window niche during cochlear implantation.ObjectiveTo compare microscopic and endoscopic visualisation of the round window membrane during cochlear implantation in 20 patients.MethodsTwenty patients who underwent cochlear implantation were included in the study. After maximum exposure of the round window, the accessibility of the round window membrane was graded according to the St Thomas Hospital classification, first by microscope and then by endoscope.ResultsWith the use of the endoscope, visualisation of the round window membrane improved in all the patients as compared to the microscope. The electrode array was inserted via a round window or extended round window approach in all but two cases; the latter cases required bony cochleostomy because of unfavourable anatomy.ConclusionThe main benefit of endoscope-assisted cochlear implantation is improved visibility of the round window region.