Martin Durisin

Recent Advances in Biodegradable Metals for Medical Sutures: A Critical Review

Sutures that biodegrade and dissolve over a period of several weeks are in great demand to stitch wounds and surgical incisions. These new materials are receiving increased acceptance across surgical procedures whenever permanent sutures and long-term care are not needed. Unfortunately, both inflammatory responses and adverse local tissue reactions in the close-to-stitching environment are often reported for biodegradable polymeric sutures currently used by the medical community. While bioabsorbable metals are predominantly investigated and tested for vascular stent or osteosynthesis applications, they also appear to possess adequate bio-compatibility, mechanical properties, and corrosion stability to replace biodegradable polymeric sutures. In this Review, biodegradable alloys made of iron, magnesium, and zinc are critically evaluated as potential materials for the manufacturing of soft and hard tissue sutures. In the case of soft tissue closing and stitching, these metals have to compete against currently available degradable polymers. In the case of hard tissue closing and stitching, biodegradable sternal wires could replace the permanent sutures made of stainless steel or titanium alloys. This Review discusses the specific materials and degradation properties required by all suture materials, summarizes current suture testing protocols and provides a well-grounded direction for the potential future development of biodegradable metal based sutures.

Outcomes and special considerations of cochlear implantation in waardenburg syndrome.

Objectives: The objective of this study was a state-of-the-art analysis of cochlear implantation in patients with Waardenburg syndrome (WS). Patients: Twenty-five patients with WS treated with cochlear implants in our department from 1990 to 2010. Interventions: The 25 patients with WS underwent 35 cochlear implantations. Main Outcome Measures: Hearing outcome was evaluated using HSM sentence test in 65 dB in quiet, Freiburg Monosyllabic Test, and categories of auditory performance for children and compared with that of a control group. Anatomic abnormalities of the inner ear were examined using magnetic resonance imaging and computed tomography of the temporal bones. Results: The mean follow-up time was 8.3 years (range, 0.3-18.3 yr). The majority achieved favorable postimplantation performance with mean HSM scores of 75.3% (range, 22.6%-99%) and Freiburg Monosyllabic Test scores of 67.8% (range, 14%-95%). However, in 4 cases, the results were less satisfactory. The comparison with the control group did not reveal any statistical significance (p = 0.56). In 6 patients (24%), behavioral disorders caused temporary difficulties during the rehabilitation procedure. Except of isolated large vestibule in 1 patient, the radiological assessment of the 50 temporal bones did not reveal any temporal bone abnormalities. Conclusion: Most patients with WS performed well with cochlear implants. However, WS is related to behavioral disorders that may cause temporary rehabilitation difficulties. Finally, temporal bone malformations that could affect cochlear implantation are notcharacteristic of WS.

Phosphodiesterase type 4 inhibitor rolipram improves survival of spiral ganglion neurons in vitro.

Sensorineural deafness is caused by damage of hair cells followed by degeneration of the spiral ganglion neurons and can be moderated by cochlear implants. However, the benefit of the cochlear implant depends on the excitability of the spiral ganglion neurons. Therefore, current research focuses on the identification of agents that will preserve their degeneration. In this project we investigated the neuroprotective effect of Rolipram as a promising agent to improve the viability of the auditory neurons. It is a pharmaceutical agent that acts by selective inhibition of the phosphodiesterase 4 leading to an increase in cyclic AMP. Different studies reported a neuroprotective effect of Rolipram. However, its significance for the survival of SGN has not been reported so far. Thus, we isolated spiral ganglion cells of neonatal rats for cultivation with different Rolipram concentrations and determined the neuronal survival rate. Furthermore, we examined immunocytologically distinct proteins that might be involved in the neuroprotective signalling pathway of Rolipram and determined endogenous BDNF by ELISA. When applied at a concentration of 0.1 nM, Rolipram improved the survival of SGN in vitro. According to previous studies, our immunocytological data showed that Rolipram application induces the phosphorylation and thereby activation of the transcription factor CREB. This activation can be mediated by the cAMP-PKA-signalling pathway as well as via ERK as a part of the MAP-kinase pathway. However, only in cultures pre-treated with BDNF, an endogenous increase of BDNF was detected. We conclude that Rolipram has the potential to improve the vitality of neonatal auditory nerve cells in vitro. Further investigations are necessary to prove the effect of Rolipram in vivo in the adult organism after lesion of the hair cells and insertion of cochlear implants.

Biocompatibility of MgF2-coated MgNd2 specimens in contact with mucosa of the nasal sinus – A long term study

Up to now, different surgical techniques and stent systems have already been developed and tested for the continuous and adequate ventilation of the frontal sinuses. However, the results achieved still remain poor. Magnesium-based implants have been successfully used in numerous clinical applications. Offering excellent biocompatibility and biodegradability it may be the ideal material for the development of novel implants of the nasal sinus. Here, we present for the first time results on the behaviour of magnesium alloy in a unique environment, i.e. in contact to the nasal mucosa, air and nasal secretion. In a prospective longitudinal study, magnesium fluoride-coated MgNd2 specimens were implanted in the frontal sinuses of 12 minipigs for the investigation of biocompatibility and of the interface between the implant and the mucosa. Endoscopic examinations, histopathological evaluation and EDX measurements were performed regularly up to 180days. Endoscopic evaluation showed focal mucosal reaction, however, without affecting the patency of the sinus. In addition, no signs of bacterial infections were observed. The EDX analyses showed a marginal but steady increase in the Mg concentration in the mucosa over 180days. Histological analysis revealed a locally confined moderate mucosal hyperplasia and unspecific inflammatory reaction. Furthermore, we did not find any osteoinductive effects of the magnesium alloy. The results indicate the excellent biocompatibility of the MgNd2 alloy in contact with nasal mucosa and provide a novel material compound and solid proof-of-principle for the development of magnesium-based nasal stents.

Primary central nervous system lymphoma presenting as bilateral tumors of the internal auditory canal.

The increasing incidence of central nervous system (CNS) lymphoma in the general population, especially in young adults with AIDS, should alert the otolaryngologist that in future there will be an even greater incidence of this rare disease. It may be responsible for hearing loss accompanied by other neurological deficits. CNS lymphoma often has a rapidly progressive course. Early diagnosis and rapid therapy are crucial for a better prognosis. We report a case of primary CNS lymphoma involving both internal auditory canals that presented with sudden deafness and disequilibrium accompanied by facial and abducens nerve palsy.

Cochlear implantation in children with bacterial meningitic deafness: The influence of the degree of ossification and obliteration on impedance and charge of the implant.

Abstract Objectives To determine impedance values and charge consumption following cochlear implantation post-meningitic deaf children depending on the grade of cochlear ossification and obliteration. Methods Post-meningitic deaf (n = 49) and control (n = 43) children treated with cochlear implants were included in the study. Impedance and charge values were calculated for each group. The degree of ossification of the cochlea was evaluated from a high-resolution computed tomography (HRCT) scan whereas the degree of obliteration was determined intraoperatively by the surgeon. Results Pneumococci were the principal pathogen responsible for bacterial meningitis, followed by meningococci. In HRCT scans, the degree of ossification was 1 and 2 in 29% of patients. The results of the intraoperative assessment of the cochlea showed obliteration grade 1 in 38% and grade 2 in 23% of cases. Children in the meningitis group showed significant higher impedances comparing to the control group. A significantly increased charge consumption was observed in patients with a grade 2 ossification when compared to those without ossification (P = 0.02). Discussion Cochlea implanted children with meningitis-related deafness exhibit higher impedances, especially in the region of the basal and middle turn, however, not depending on the degree of cochlear ossification. High impedances and charge in the meningitis group may be explained by alterations in the central auditory pathway or on the electrode surface. Conclusion To optimize the outcome in post-meningitic deaf children, surgery is advisable at an early stage prior to the onset of cochlear ossification.

Biodegradable nasal stents (MgF2‐coated Mg–2 wt %Nd alloy)—A long‐term in vivo study

Despite innovative surgical techniques and use of current frontal sinus stents from different materials, the problem of treatment failure with consecutive reoperation remains present. The aim of our study is to investigate biocompatibility, degradation kinetics, and functionality of a newly developed fluoride-coated magnesium-based nasal stent. A minipig anatomy of frontal sinus adapted design and an external surgical approach were developed and established. The functionality of the stents was evaluated endoscopically. The stent-tissue blocks were analysed after 90 and 180 days using microcomputed tomography (µ-CT), histology, scanning electron microscopy (SEM), and energy-dispersive X-ray spectroscopy (EDS). Functional evaluation revealed an unobstructed stent lumen in all cases. Histological analysis showed moderate mucosal hyperplasia with a mild, nonspecific inflammatory response, and nonosteoconductive effect. Rejection reactions or necrosis did not occur. The volumetric analysis of the stents showed 51% volume loss after 180 days. The EDS analysis did not detect any neodymium (Nd) in the mucosa or bone. The Mg-2 wt % Nd stents are a promising option when treating the narrow passages following paranasal sinus surgery. In particular, its good biocompatibility and good functionality facilitate the re-epithelization of these constricted passages.

Platinum corrosion products from electrode contacts of human cochlear implants induce cell death in cell culture models

Despite the technological progress made with cochlear implants (CI), impedances and their diagnosis remain a focus of interest. Increases in impedance have been related to technical defects of the electrode as well as inflammatory and/or fibrosis along the electrode. Recent studies have demonstrated highly increased impedances as the result of corroded platinum (Pt) electrode contacts. This in vitro study examined the effects of Pt ions and compounds generated by corrosion of the electrode contacts of a human CI on cell metabolism. Since traces of solid Pt in surrounding cochlear tissues have been reported, the impact of commercially available Pt nanoparticles (Pt-NP, size 3 nm) on the cell culture model was also determined. For this purpose, the electrode contacts were electrically stimulated in a 0.5% aqueous NaCl solution for four weeks and the mass fraction of the platinum dissolute (Pt-Diss) was determined by mass spectrometry (ICP-MS). Metabolic activity of the murine fibroblasts (NIH 3T3) and the human neuroblastoma (SH-SY5Y) cells was determined using the WST-1 assay following exposure to Pt-Diss and Pt-NP. It was found that 5–50 μg/ml of the Pt-NP did not affect the viability of both cell types. In contrast, 100 μg/ml of the nanoparticles caused significant loss in metabolic activity. Furthermore, transmission electron microscopy (TEM) revealed mitochondrial swelling in both cell types indicating cytotoxicity. Additionally, TEM demonstrated internalized Pt-NP in NIH 3T3 cells in a concentration dependent manner, whereas endocytosis in SH-SY5Y cells was virtually absent. In comparison with the Pt-NP, the corrosion products (Pt-Diss) with concentrations between 1.64 μg/ml and 8.2 μg/ml induced cell death in both cell lines in a concentration dependent manner. TEM imaging revealed both mitochondrial disintegration and swelling of the endoplasmic reticulum, suggesting that Pt ions trigger cytotoxicity in both NIH 3T3 and SH-SY5Y cell lines by interacting with the respiratory chain.

Microenvironmental support for cell delivery to the inner ear.

Abstract Transplantation of mesenchymal stromal cells (MSC) presents a promising approach not only for the replacement of lost or degenerated cells in diseased organs but also for local drug delivery. It can potentially be used to enhance the safety and efficacy of inner ear surgeries such as cochlear implantation. Options for enhancing the effects of MSC therapy include modulating cell behaviour with customized bio‐matrixes or modulating their behaviour by ex vivo transfection of the cells with a variety of genes. In this study, we demonstrate that MSC delivered to the inner ear of guinea pigs or to decellularized cochleae preferentially bind to areas of high heparin concentration. This presents an opportunity for modulating cell behaviour ex vivo. We evaluated the effect of carboxymethylglucose sulfate (Cacicol®), a heparan sulfate analogue on spiral ganglion cells and MSC and demonstrated support of neuronal survival and support of stem cell proliferation. HighlightsTransplantation of MSC to the inner ear of guinea pigs showed integration to the lateral wall and scala tympani.Cultivation of MSC on decellularized cochleae confirmed binding to areas of high heparin concentration.Carboxymethylglucose sulphate supported survival of spiral ganglion cells and proliferation of stem cells in vitro.Cacicol® is a suitable matrix for adhesion of spiral ganglion cells.

Degradation of MgF2-Coated and Uncoated MgNd2 Specimens in Contact with Nasal Mucosa

The magnesium-neodymium alloy MgNd2 offers an elongation of 30%. Therefore, it is well suited as a material for resorbable stents which can be used for treating chronic sinusitis. While the alloy’s corrosion properties were already investigated in vitro, the present study focuses on the in vivo degradation behavior of fluoride-coated and uncoated specimens in direct contact with porcine nasal mucosa during a period of 180 days. The study showed a promising and controlled biodegradation, which was investigated by measurements of the MgNd2 specimens’ mass and volume losses as well as element analyses on the surface to obtain information about the composition of the degradation layer. The degradation rates of the uncoated samples in direct contact with the physiological tissue showed a maximum during the first 45 days which then decreased for the remaining implantation period. In contrast, the degradation rates of the fluoride-coated samples increased gradually during the implantation duration.