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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).

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.

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.