Thomas Eickner

Degradable polymers, such as poly(L-lactide) (PLLA), are widely investigated for biomedical applications, including drug delivery systems and temporary implants. Their functionality can be expanded by incorporating degradable metal microparticles that may influence degradation behaviour and enable additional surface modification strategies. In this study, the feasibility of composites consisting of PLLA and biodegradable iron microparticles was investigated. Composites were fabricated by solvent casting, providing a gentle alternative to thermal processing methods, which often compromise polymer integrity. Composites were evaluated by thermogravimetric analysis, differential scanning calorimetry, scanning electron microscopy (SEM), tensile testing, dynamic mechanical analysis, and X-ray photoelectron spectroscopy (XPS). Incorporation of iron altered thermal behaviour and crystallinity of PLLA, indicating interactions between polymer matrix and dispersed metal phase that may affect degradation kinetics and material stability. While iron addition reduced Young’s modulus, tensile strength, and elongation at break, composites maintained sufficient structural integrity for potential biomedical applications. XPS and SEM confirmed the embedding of particles within the polymer matrix, enabling potential post-processing approaches. In vitro direct contact and eluate tests demonstrated good cell viability, whereas exposure to free iron particles resulted in dose- and time-dependent cytotoxic effects. Overall, the results demonstrate the feasibility of solvent-cast PLLA–iron composites for resorbable biomedical applications.

Postoperative scarring following trabeculectomy, a glaucoma surgery, often leads to failure, necessitating biodegradable drug delivery systems for sustained antifibrotic release. This study explores γ-cyclodextrin/hyaluronic acid (γ- CD/HA) copolymers as potential drug depots, evaluating their degradation kinetics under physiological conditions. Copolymers with 0% and 75% γ-CD were synthesized via base-catalyzed crosslinking with 1,4-butanediol diglycidyl ether (BDDE). Degradation was assessed by incubating samples in Sørensen buffer (pH 7.4) with lysozyme, monitoring mass loss over 14 days. Both systems degraded, yet the 75% CD copolymer exhibited a significantly slower, linear degradation profile compared to the rapidly degrading 0% CD system. Morphological analysis revealed increased swelling in the 75% CD samples, suggesting cleavage of intermolecular crosslinks. Gravimetric analysis indicated a mass loss of approximately 50% for the 75% CD system by day 14. The tunable degradation kinetics of these γ-CD/HA copolymers suggest promise for controlled drug release applications in glaucoma, warranting further investigation into drug loading and release profiles.

A novel phenylalanine/ valine ethyl ester cosubstituted polyorganophosphazene, incorporating triethyl citrate as plasticizer, is being investigated for its degradability. Films were solvent casted, and allowed to degrade for 4 weeks at an elevated temperature of 50 °C in water and two HEPES buffered solutions with pH values 6.8 and 7.4, respectively. The degradation of the samples in pure water occurred at a significantly accelerated rate compared to the samples incubated in HEPES buffer. Furthermore, based on their influence on degradation, the pH values of the media used were assessed.

Cochlear implants are well established devices for treating severe hearing loss. However, due to the trauma caused by the insertion of the electrode and the subsequent formation of connective tissue, their clinical effectiveness varies. The aim of the current study was to achieve a long-term reduction in connective tissue growth and impedance by combining surface patterns on the electrode array with a poly-L-lactide coating containing 20% diclofenac. Three groups of six guinea pigs each (control, structure, structure with diclofenac in the coating) were implanted for four weeks. The hearing thresholds were measured before implantation and after 28 days, and impedances were monitored over time. After histological preparation, connective tissue growth and spiral ganglion neuron (SGN) survival were quantified. The hearing thresholds and impedances increased over time in all groups, showing no significant differences. The treatment groups showed increased damage in the cochlea, which appeared to be caused by the elevated parts of the microstructures. This seems to be amplified by the trauma model used in the current study. The impedances correlated with connective tissue growth near the electrode contacts. In addition, SGN survival was negatively correlated with the presence of connective tissue, both of which highlight the importance of successfully reducing connective tissue formation after cochlear implantation.

Background: Preserving residual hearing after cochlear implant (CI) surgery remains a crucial challenge. The application of dexamethasone (DEX) has been proven to positively affect residual hearing. To deliver DEX in a localized and controlled way, a round window niche implant (RNI), allowing drug diffusion via the round window membrane into the cochlea, may be used. To prove this concept, an RNI for guinea pigs as a CI-trauma model was manufactured by molding and tested for its drug release in vitro and biological effects in vivo. Methods: The RNIs were molded using silicone containing 10% DEX. Release was analyzed over time using high-performance liquid chromatography (HPLC). Fourteen adult guinea pigs were randomly assigned to two groups (CI or CI + RNI group). All animals received a unilateral CI electrode insertion trauma followed by CI insertion. The CI + RNI group was additionally implanted with an RNI containing 10% DEX. Animals were followed up for 4 weeks. Acoustically evoked auditory brainstem response and impedance measurement, micro-computed tomography (µCT) imaging, and histology were performed for evaluation. Results: DEX was released for more than 250 days in vitro, with an initial burst followed by a slower release over time. Comparing the hearing threshold shift (from day 0 to day 28) of the CI and CI + RNI groups, significant differences were observed at 32 and 40 kHz. The impedance shift at basal contacts was lower in the CI + RNI group than in the CI group. Moreover, the fibrosis in the lower basal turn was reduced in the CI + RNI group in contrast to the CI group. Conclusions: The RNI containing 10% DEX has anti-inflammatory potential concerning fibrosis inhibition and has beneficial effects on hearing preservation at high frequencies.

For the in vitro examination of the effects on cells and tissues of metal ions derived from implants by wear and corrosion, a system is needed to release metal ions in a controlled and sustained manner. As small concentrations may have an impact on biological systems, a corresponding slow release over a defined period of time is necessary. Here, a manufacturing method of polymeric Poly(L-lactic acid) (PLLA) films with incorporated cobalt ions via dip coating is reported. The establishment of two analytical methods for the detection and quantification of cobalt ions is shown. High performance liquid chromatography enables cobalt quantification over a concentration range of 0.33 μg/mL up to 33 μg/mL in sample solutions. Extraction and detection of cobalt ions from solvent cast PLLA-cobalt-films shows the feasibility of the manufacturing method. Initial biocompatibility tests with manufactured PLLA-cobaltfilms showed no effects on adipose derived primary mesenchymal stem cells (adMSCs).

Several physico-chemical modifications have been developed to improve cell contact with prosthetic oral implant surfaces. The activation with non-thermal plasmas was one option. Previous studies found that gingiva fibroblasts on laser-microstructured ceramics were hindered in their migration into cavities. However, after argon (Ar) plasma activation, the cells concentrated in and around the niches. The change in surface properties of zirconia and, subsequently, the effect on cell behavior is unclear. In this study, polished zirconia discs were activated by atmospheric pressure Ar plasma using the kINPen^®09 jet for 1 min. Surfaces were characterized by scanning electron microscopy, X-ray photoelectron spectroscopy (XPS), and water contact angle. In vitro studies with human gingival fibroblasts (HGF-1) focused on spreading, actin cytoskeleton organization, and calcium ion signaling within 24 h. After Ar plasma activation, surfaces were more hydrophilic. XPS revealed decreased carbon and increased oxygen, zirconia, and yttrium content after Ar plasma. The Ar plasma activation boosted the spreading (2 h), and HGF-1 cells formed strong actin filaments with pronounced lamellipodia. Interestingly, the cells’ calcium ion signaling was also promoted. Therefore, argon plasma activation of zirconia seems to be a valuable tool to bioactivate the surface for optimal surface occupation by cells and active cell signaling.

A novel approach for the long-term medical treatment of the inner ear is the diffusion of drugs through the round window membrane from a patient-individualized, drug-eluting implant, which is inserted in the middle ear. In this study, drug-loaded (10 wt% Dexamethasone) guinea pig round window niche implants (GP-RNIs, ~1.30 mm × 0.95 mm × 0.60 mm) were manufactured with high precision via micro injection molding (µIM, T_mold = 160 °C, crosslinking time of 120 s). Each implant has a handle (~3.00 mm × 1.00 mm × 0.30 mm) that can be used to hold the implant. A medical-grade silicone elastomer was used as implant material. Molds for µIM were 3D printed from a commercially available resin (T_G = 84 °C) via a high-resolution DLP process (xy resolution of 32 µm, z resolution of 10 µm, 3D printing time of about 6 h). Drug release, biocompatibility, and bioefficacy of the GP-RNIs were investigated in vitro. GP-RNIs could be successfully produced. The wear of the molds due to thermal stress was observed. However, the molds are suitable for single use in the µIM process. About 10% of the drug load (8.2 ± 0.6 µg) was released after 6 weeks (medium: isotonic saline). The implants showed high biocompatibility over 28 days (lowest cell viability ~80%). Moreover, we found anti-inflammatory effects over 28 days in a TNF-α-reduction test. These results are promising for the development of long-term drug-releasing implants for human inner ear therapy.

A novel approach for the long-term medical treatment of the inner ear is the diffusion of drugs through the round window membrane from a patient-individualized, drug-eluting implant, which is inserted in the middle ear. In this study, drug-loaded (10 wt% Dexamethasone) guinea pig round window niche implants (GP-RNIs, ~1.30 mm x 0.95 mm x 0.60 mm) were manufactured with high precision via micro injection molding (µIM, Tmold = 160 °C, crosslinking time of 120 s). The medical grade silicone elastomer MED-4244 (NuSil Technology LLC, Radnor, PA, USA) was used. Molds for µIM were 3D printed from a commercially available resin PlasGRAY V2 (Asiga, Alexandria, Australia, TG = 84 °C) via a high-resolution DLP process (xy-resolution of 32 µm, z-resolution of 10 µm, 3D printing time of about 6 h). Drug release, biocompatibility, and bio-efficacy of the GP-RNIs were investigated in vitro. GP-RNIs could be successfully produced. Wear of the molds due to thermal stress was observed. However, the molds are suitable for single use in the µIM process. About 10% of the drug load (8.2 ± 0.6 µg) was released after 6 weeks (medium: isotonic saline). The implants showed high biocompatibility over a time of 28 days (lowest cell viability ~80%). Moreover, we found anti-inflammatory effects over a time of 28 days in a TNF-α-reduction test. These results are promising for the development of long-term drug-releasing implants for human inner ear therapy.

Cochlear implants are well established to treat severe hearing impairments. Despite many different approaches to reduce the formation of connective tissue after electrode insertion and to keep electrical impedances low, results are not yet satisfying. Therefore, the aim of the current study was to combine the incorporation of 5% dexamethasone in the silicone body of the electrode array with an additional polymeric coating releasing diclofenac or the immunophilin inhibitor MM284, some anti-inflammatory substances not yet tested in the inner ear. Guinea pigs were implanted for four weeks and hearing thresholds were determined before implantation and after the observation time. Impedances were monitored over time and, finally, connective tissue and the survival of spiral ganglion neurons (SGNs) were quantified. Impedances increased in all groups to a similar extent but this increase was delayed in the groups with an additional release of diclofenac or MM284. Using Poly-L-lactide (PLLA)-coated electrodes, the damage caused during insertion was much higher than without the coating. Only in these groups, connective tissue could extend to the apex of the cochlea. Despite this, numbers of SGNs were only reduced in PLLA and PLLA plus diclofenac groups. Even though the polymeric coating was not flexible enough, MM284 seems to especially have potential for further evaluation in connection with cochlear implantation.