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.

Polyphosphazenes are a unique class of polymers, notable for their versatile functionalization and distinctive properties arising from their alternating phosphorus-nitrogen backbone. However, the synthesis of their primary precursor, poly(dichlorophosphazene) ([NPCl2]n), is notoriously delicate and poorly understood, limiting broader adoption. Herein, we reinvestigate the controlled polymerization of Me3Si─N═PCl3 using quantum mechanical calculations to elucidate its underlying mechanism. Guided by these insights, we optimized the experimental conditions and achieved significantly higher molecular weights than previously reported for this polymerization route. Polymerization occurs at ambient temperature only upon addition of a cationic initiator, such as Ph3PCl2, yielding [NPCl2]n chains of varying lengths. Experiments and DFT calculations indicate that initiation proceeds via three key steps: (i) dissociation of Ph3PCl2 into [Ph3PCl]+ and Cl- ions, dependent on the reaction medium; (ii) nucleophilic attack of Cl- on Me3Si─N═PCl3, producing [N═PCl3]- and eliminating Me3SiCl; (iii) reaction of [N═PCl3]- with [Ph3PCl]+ to form Ph3P─NPCl4, which dissociates to generate additional reactive species, propagating chain growth. The elimination of Me3SiCl, concurrent with [N═PCl3]- formation, constitutes the rate-limiting step. Accordingly, this type of polymerization can be described as a chloride-catalyzed cationic process. These findings provide a detailed mechanistic understanding of poly(dichlorophosphazene) formation and offer a basis for optimizing reaction conditions to achieve controlled polymerization.

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.

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.

Periodontitis is a prevalent chronic inflammatory disease that requires effective long-term treatment strategies. Current antimicrobial formulations, such as Chlorhexidine (CHX) gels and antibiotic-based inserts, often suffer from short retention times and uncontrolled drug release, limiting their therapeutic efficacy. To address these challenges, we developed a biodegradable, in situ cross-linked CHX depot incorporating a bifunctional reactive cross-linker, triethylene glycol bis(dilactic acid) bis(hexamethylene diisocyanate) (TELANCO). The synthesized TELA-NCO was mixed with commercially available CHX gel to form an injectable paste that polymerizes within 7 hours into a stable depot. HPLC release studies demonstrated sustained CHX release for over 35 days, significantly reducing initial burst effects. In vitro cytocompatibility tests revealed expected concentrationdependent CHX cytotoxicity, but good biocompatibility of the cross-linker. This injectable, degradable depot system offers a promising alternative for localized antimicrobial therapy in periodontology and endodontics, eliminating the need for secondary removal.

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.

To study the effects of metal ions on cells and tissues caused by wear and corrosion of implants in vitro, a system is required that releases metal ions in a controlled and sustained manner. As small concentrations can have an impact on biological systems, a correspondingly slow release over a defined period of time is required. A method for the manufacturing of polymeric poly(L-lactic acid) (PLLA) films with incorporated cobalt microparticles by dip coating is reported. Two analytical methods are established to demonstrate the detection and quantification of cobalt particles. Thermogravimetric analysis allows the quantification of cobalt particles. Scanning electron microscope images can be used to determine the distribution and number of particles of different size ranges.

Poly(ethylene glycol) diacrylate (PEGDA) is a common polymer in the field of biomedical engineering and can be used for the production of drug delivery systems (DDS). The main advantages of PEGDA are biocompatibility and the ability to alter the physical and chemical properties, thereby ensuring individualized drug release behaviour. The processing of PEGDA via inkjet printing is relevant for the production of DDS. This can be challenging due to the high viscosity of pure PEGDA. In this work, PEGDA, with a molecular weight of 250 g/mol (PEGDA250), was inkjet printed using a Nanoplotter 2.1 with a piezoelectric heatable NanoTip HV-J-H printhead (GeSiM mbH, Radeberg, Germany) at different voltages and temperatures. Droplet generation was analysed in terms of droplet volume and angle deviations. PEGDA250 can be inkjet printed reproducibly in a voltage range of 60 V - 80 V at room temperature (20 °C) or heated up to 38 °C. The average volume of heated (38 °C) PEGDA250 droplets was approximately 110 pl - 150 pl higher than the droplet volume of PEGDA250 in the unheated state. The average angle deviations of main and satellite droplets were mostly < 3°. Increasing voltage or excessive heating of more than 38 °C caused greater instabilities in the droplet generation as well as larger satellite droplets which can affect the accuracy negatively. The studies have shown that PEGDA250 can be processed via inkjet printing and thus can be used as a drug carrier for DDS without the need for mixing with a solvent.

Background There exists an unfulfilled requirement for effective cochlear pharmacotherapy. Controlled local drug delivery could lead to effective bioavailability. The round window niche (RWN), a cavity in the middle ear, is connected to the cochlea via a membrane through which drug can diffuse. We are developing individualized drug-eluting RWN implants (RNIs). To test their effectiveness in guinea pigs, a commonly used model in cochlear pharmacology studies, it is first necessary to develop guinea pig RNIs (GP-RNI).Methods Since guinea pigs do not have a RWN such as it is present in humans and to reduce the variables in in vivo studies, a one-size-fits-all GP-RNI model was designed using 12 data sets of Dunkin-Hartley guinea pigs. The model was 3D-printed using silicone. The accuracy and precision of printing, distribution of the sample ingredient dexamethasone (DEX), biocompatibility, bio-efficacy, implantability and drug release were tested in vitro. The GP-RNI efficacy was validated in cochlear implant-traumatized guinea pigs in vivo.Results The 3D-printed GP-RNI was precise, accurate and fitted in all tested guinea pig RWNs. DEX was homogeneously included in the silicone. The GP-RNI containing 1% DEX was biocompatible, bio-effective and showed a two-phase and sustained DEX release in vitro, while it reduced fibrous tissue growth around the cochlear implant in vivo.Conclusions We developed a GP-RNI that can be used for precise inner ear drug delivery in guinea pigs, providing a reliable platform for testing the RNI’s safety and efficacy, with potential implications for future clinical translation.

Antifibrotic treatment during glaucoma surgery leads to an improved outcome for patients. Drug delivery systems for placement under the subconjuctiva after surgery made of cyclodextrins and crosslinked with Epichlorohydin were loaded with Josamycin and tested in vivo. After subconjunctival application in three New Zealand White rabbits, blood samples were taken by the means of Mitra devices at defined time points. Determination of blood levels of Josamycin was performed using liquid chromatography mass spectrometry. Detection of Josamycin was achieved during 48 h suggesting a sustained release over the course of this study.

Glaucoma is the leading cause of blindness worldwide. However, its surgical treatment, in particular via trabeculectomy, can be complicated by fibrosis. In current clinical practice, application of the drug, Mitomycin C, prevents or delays fibrosis, but can lead to additional side effects, such as bleb leakage and hypotony. Previous in silico drug screening and in vitro testing has identified the known antibiotic, josamycin, as a possible alternative antifibrotic medication with potentially fewer side effects. However, a suitable ocular delivery mechanism for the hydrophobic drug to the surgical site does not yet exist. Therefore, the focus of this paper is the development of an implantable drug delivery system for sustained delivery of josamycin after glaucoma surgery based on crosslinked γ-cyclodextrin. γ-Cyclodextrin is a commonly used solubilizer which was shown to complex with josamycin, drastically increasing the drug’s solubility in aqueous solutions. A simple γ-cyclodextrin crosslinking method produced biocompatible hydrogels well-suited for implantation. The crosslinked γ − cyclodextrin retained the ability to form complexes with josamycin, resulting in a 4-fold higher drug loading efficiency when compared to linear dextran hydrogels, and prolonged drug release over 4 days.

Hydrogels are extensively used in the biomedical field due to their highly valued properties, biocompatibility and antimicrobial activity and resistance to rheological stress. However, determining an efficient sterilization protocol that does not compromise the functional properties of hydrogels is one of the challenges researchers face when developing a material for a medical application. In this work, conventional sterilization methods (steam-, radiation- and gas sterilization) were investigated regarding the influence on the degree of swelling, mechanical performance and chemical effects on the poly 3-sulfopropyl acrylate potassium (pAESO3) hydrogel, which is a promising representative for biomedical engineering applications. In summary, no significant changes in the gel properties were observed after sterilization, showing the potential of the selected hydrogel for biomedical applications.

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.

Ultrafine membranes produced via electrospinning exhibit multidirectional strength and elasticity. In contrast to compact polymer films or coatings, they also have an exceptional surface-to-volume ratio, which makes them attractive carrier structures for many biomedical applications, also with regard to the release of bioactive substances. Within the scope of an orientation study we investigated the mechanical properties of biodegradable nanofibrous carrier materials using tensile specimens made of nanoparticle loaded polydioxanone (PDO), polylactide (PLA), polyglycolide (PGA) and polybutylene succinate (PBS). Mass loss and tensile strength as well as pH changes during incubation at 37°C in an unbuffered isotonic saline solution with 10% ethanol were examined within defined time periods up to 33 days. Initial tests with several antibacterial additives, especially TiO2 and Ag nanoparticles and octenidine were performed.

Inkjet printing is a versatile tool for the precise positioning of droplets that is used in many application areas such as 3D printing, biotechnology or pharmacy. This work focused on comparing the inkjet printability of different drug solutions of celecoxib (CLX), a non-steroidal anti-inflammatory drug, to produce drug depots in medical implants. CLX was dissolved in dimethyl sulfoxide (DMSO), poly(ethylene glycol) diacrylate (PEGDA) and a mixture of DMSO and PEGDA in a ratio of 1:1. The pure solvents and the drug solutions were inkjet printed using a Nanoplotter 2.1 with the NanoTip J printhead (GeSiM mbH, Radeberg, Germany). The voltage was varied from 60 V to 150 V using a step size of 5 V. Droplet volume and the trajectory of the droplets were investigated. For DMSO, DMSO-CLX, DMSO-PEGDA and DMSOPEGDA- CLX, reproducible droplet formation occurred with a droplet volume of approximately 300 pl - 500 pl and not more than one satellite droplet in a voltage range between 60 V to 80 V. Inkjet printing of PEGDA and PEGDA-CLX was not reproducible in the range of 60 V to 150 V. DMSO, DMSOPEGDA, DMSO-CLX and DMSO-PEGDA-CLX showed a high inkjet printability. In contrast, inkjet printability of PEGDA and PEGDA-CLX was very limited.

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.

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).

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, Tmold = 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 (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 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.

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.

Hydrogels are 3D polymeric networks, which exhibit properties such as softness, viscoelasticity and their ability to absorb large amounts of water. These characteristics make them exceptionally suitable in biomedicine as e.g. tissue scaffolds, drug delivery systems, wound dressings or contact lenses. One of these hydrogels is the biocompatible, hydrophilic and photopolymerizable poly(ethylene glycol) diacrylate (PEGDA). It is used in different biomedical applications due to its tunable mechanical characteristics. In our study, the mechanical properties of different PEGDA hydrogel compositions with variyng molecular masses and contents of water/methanol, were investigated. Different compositions containing 20 m%, 30 m% or 40 m% of PEGDA4K(4,000 g/mol), PEGDA10K(10,000 g/mol) or PEGDA20K(20,000 g/mol) in ultrapure water/methanol (1:2) were produced. Dumbbell-shaped samples were prepared in molds via photopolymerization in a UV chamber. Lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP) was used as photoinitiator (0.5% w/w). The mechanical testing was performed using a uniaxial testing system. The obtained results showed averagely 78% higher tensile strength (σmax) values for 30 m% and 40 m% samples in comparison with 20 m% samples for all of the tested polymers. PEGDA20K30 m% samples showed the highest σmax among all of the samples with 12.8 MPa. All of the PEGDA20K samples exhibited the highest elongation at break (εB) values (up to 958%), whereas the lowest values were found for PEGDA4K(up to 105%). The obtained stress-strain curves for most of the samples were typical for deformable, amorphous polymers with a deformation upon reaching a critical stress point. The PEGDA materials showed variable mechanical characteristics according to changing molecular mass or polymer concentration. These promising results showed that it should be possible to compose scaffolds with desired mechanical stability according to the needed application.