Micro Injection Molding of Drug-Loaded Round Window Niche Implants for an Animal Model Using 3D-Printed Molds
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...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-05-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/15/6/1584 |
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| author | Robert Mau Thomas Eickner Gábor Jüttner Ziwen Gao Chunjiang Wei Nicklas Fiedler Volkmar Senz Thomas Lenarz Niels Grabow Verena Scheper Hermann Seitz |
| author_facet | Robert Mau Thomas Eickner Gábor Jüttner Ziwen Gao Chunjiang Wei Nicklas Fiedler Volkmar Senz Thomas Lenarz Niels Grabow Verena Scheper Hermann Seitz |
| author_sort | Robert Mau |
| collection | DOAJ |
| description | 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<sub>mold</sub> = 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<sub>G</sub> = 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. |
| first_indexed | 2024-03-11T02:03:09Z |
| format | Article |
| id | doaj.art-5be2ca9a943b493db94e194655b5b954 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-11T02:03:09Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-5be2ca9a943b493db94e194655b5b9542023-11-18T12:03:31ZengMDPI AGPharmaceutics1999-49232023-05-01156158410.3390/pharmaceutics15061584Micro Injection Molding of Drug-Loaded Round Window Niche Implants for an Animal Model Using 3D-Printed MoldsRobert Mau0Thomas Eickner1Gábor Jüttner2Ziwen Gao3Chunjiang Wei4Nicklas Fiedler5Volkmar Senz6Thomas Lenarz7Niels Grabow8Verena Scheper9Hermann Seitz10Microfluidics, Faculty of Mechanical Engineering and Marine Technology, University of Rostock, Justus-von-Liebig Weg 6, 18059 Rostock, GermanyInstitute for Biomedical Engineering, University Medical Center Rostock, Friedrich-Barnewitz-Straße 4, 18119 Rostock, GermanyKunststoff-Zentrum in Leipzig gGmbH (KUZ), Erich-Zeigner-Allee 44, 04229 Leipzig, GermanyLower Saxony Center for Biomedical Engineering, Implant Research and Development (NIFE), Department of Otorhinolaryngology, Head and Neck Surgery, Hannover Medical School, Stadtfelddamm 34, 30625 Hannover, GermanyLower Saxony Center for Biomedical Engineering, Implant Research and Development (NIFE), Department of Otorhinolaryngology, Head and Neck Surgery, Hannover Medical School, Stadtfelddamm 34, 30625 Hannover, GermanyInstitute for Biomedical Engineering, University Medical Center Rostock, Friedrich-Barnewitz-Straße 4, 18119 Rostock, GermanyInstitute for Biomedical Engineering, University Medical Center Rostock, Friedrich-Barnewitz-Straße 4, 18119 Rostock, GermanyLower Saxony Center for Biomedical Engineering, Implant Research and Development (NIFE), Department of Otorhinolaryngology, Head and Neck Surgery, Hannover Medical School, Stadtfelddamm 34, 30625 Hannover, GermanyInstitute for Biomedical Engineering, University Medical Center Rostock, Friedrich-Barnewitz-Straße 4, 18119 Rostock, GermanyLower Saxony Center for Biomedical Engineering, Implant Research and Development (NIFE), Department of Otorhinolaryngology, Head and Neck Surgery, Hannover Medical School, Stadtfelddamm 34, 30625 Hannover, GermanyMicrofluidics, Faculty of Mechanical Engineering and Marine Technology, University of Rostock, Justus-von-Liebig Weg 6, 18059 Rostock, GermanyA 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<sub>mold</sub> = 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<sub>G</sub> = 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.https://www.mdpi.com/1999-4923/15/6/1584micro injection molding3D printingrapid toolingdigital light processingimplantdrug delivery system |
| spellingShingle | Robert Mau Thomas Eickner Gábor Jüttner Ziwen Gao Chunjiang Wei Nicklas Fiedler Volkmar Senz Thomas Lenarz Niels Grabow Verena Scheper Hermann Seitz Micro Injection Molding of Drug-Loaded Round Window Niche Implants for an Animal Model Using 3D-Printed Molds Pharmaceutics micro injection molding 3D printing rapid tooling digital light processing implant drug delivery system |
| title | Micro Injection Molding of Drug-Loaded Round Window Niche Implants for an Animal Model Using 3D-Printed Molds |
| title_full | Micro Injection Molding of Drug-Loaded Round Window Niche Implants for an Animal Model Using 3D-Printed Molds |
| title_fullStr | Micro Injection Molding of Drug-Loaded Round Window Niche Implants for an Animal Model Using 3D-Printed Molds |
| title_full_unstemmed | Micro Injection Molding of Drug-Loaded Round Window Niche Implants for an Animal Model Using 3D-Printed Molds |
| title_short | Micro Injection Molding of Drug-Loaded Round Window Niche Implants for an Animal Model Using 3D-Printed Molds |
| title_sort | micro injection molding of drug loaded round window niche implants for an animal model using 3d printed molds |
| topic | micro injection molding 3D printing rapid tooling digital light processing implant drug delivery system |
| url | https://www.mdpi.com/1999-4923/15/6/1584 |
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