Individualized, Additively Manufactured Drug-Releasing External Ear Canal Implant for Prevention of Postoperative Restenosis: Development, In Vitro Testing, and Proof of Concept in an Individual Curative Trial
Postoperative restenosis in patients with external ear canal (EEC) atresia or stenosis is a common complication following canaloplasty. Our aim in this study was to explore the feasibility of using a three dimensionally (3D)-printed, patient-individualized, drug ((dexamethasone (DEX)), and ciproflox...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-06-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/14/6/1242 |
| _version_ | 1797483280542466048 |
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| author | Farnaz Matin-Mann Ziwen Gao Jana Schwieger Martin Ulbricht Vanessa Domsta Stefan Senekowitsch Werner Weitschies Anne Seidlitz Katharina Doll Meike Stiesch Thomas Lenarz Verena Scheper |
| author_facet | Farnaz Matin-Mann Ziwen Gao Jana Schwieger Martin Ulbricht Vanessa Domsta Stefan Senekowitsch Werner Weitschies Anne Seidlitz Katharina Doll Meike Stiesch Thomas Lenarz Verena Scheper |
| author_sort | Farnaz Matin-Mann |
| collection | DOAJ |
| description | Postoperative restenosis in patients with external ear canal (EEC) atresia or stenosis is a common complication following canaloplasty. Our aim in this study was to explore the feasibility of using a three dimensionally (3D)-printed, patient-individualized, drug ((dexamethasone (DEX)), and ciprofloxacin (cipro))-releasing external ear canal implant (EECI) as a postoperative stent after canaloplasty. We designed and pre-clinically tested this novel implant for drug release (by high-performance liquid chromatography), biocompatibility (by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay), bio-efficacy (by the TNF-α (tumor necrosis factor-alpha)-reduction test (DEX) and inhibition zone test (for cipro)), and microbial contamination (formation of turbidity or sediments in culture medium). The EECI was implanted for the first time to one patient with a history of congenital EEC atresia and state after three canaloplasties due to EEC restenosis. The preclinical tests revealed no cytotoxic effect of the used materials; an antibacterial effect was verified against the bacteria <i>Staphylococcus aureus</i> and <i>Pseudomonas aeruginosa</i>, and the tested UV-irradiated EECI showed no microbiological contamination. Based on the test results, the combination of silicone with 1% DEX and 0.3% cipro was chosen to treat the patient. The EECI was implantable into the EEC; the postoperative follow-up visits revealed no otogenic symptoms or infections and the EECI was explanted three months postoperatively. Even at 12 months postoperatively, the EEC showed good epithelialization and patency. Here, we report the first ever clinical application of an individualized, drug-releasing, mechanically flexible implant and suggest that our novel EECI represents a safe and effective method for postoperatively stenting the reconstructed EEC. |
| first_indexed | 2024-03-09T22:45:41Z |
| format | Article |
| id | doaj.art-a23ea856672b4fa4b1f865d988de10b1 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-09T22:45:41Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-a23ea856672b4fa4b1f865d988de10b12023-11-23T18:30:33ZengMDPI AGPharmaceutics1999-49232022-06-01146124210.3390/pharmaceutics14061242Individualized, Additively Manufactured Drug-Releasing External Ear Canal Implant for Prevention of Postoperative Restenosis: Development, In Vitro Testing, and Proof of Concept in an Individual Curative TrialFarnaz Matin-Mann0Ziwen Gao1Jana Schwieger2Martin Ulbricht3Vanessa Domsta4Stefan Senekowitsch5Werner Weitschies6Anne Seidlitz7Katharina Doll8Meike Stiesch9Thomas Lenarz10Verena Scheper11Department of Otorhinolaryngology, Head and Neck Surgery, Lower Saxony Center for Biomedical Engineering, Implant Research and Development (NIFE), Hannover Medical School, Stadtfelddamm 34, 30625 Hannover, GermanyDepartment of Otorhinolaryngology, Head and Neck Surgery, Lower Saxony Center for Biomedical Engineering, Implant Research and Development (NIFE), Hannover Medical School, Stadtfelddamm 34, 30625 Hannover, GermanyDepartment of Otorhinolaryngology, Head and Neck Surgery, Lower Saxony Center for Biomedical Engineering, Implant Research and Development (NIFE), Hannover Medical School, Stadtfelddamm 34, 30625 Hannover, GermanyCenter of Drug Absorption and Transport, Department of Biopharmacy and Pharmaceutical Technology, Institute of Pharmacy, University of Greifswald, 17489 Greifswald, GermanyCenter of Drug Absorption and Transport, Department of Biopharmacy and Pharmaceutical Technology, Institute of Pharmacy, University of Greifswald, 17489 Greifswald, GermanyCenter of Drug Absorption and Transport, Department of Biopharmacy and Pharmaceutical Technology, Institute of Pharmacy, University of Greifswald, 17489 Greifswald, GermanyCenter of Drug Absorption and Transport, Department of Biopharmacy and Pharmaceutical Technology, Institute of Pharmacy, University of Greifswald, 17489 Greifswald, GermanyCenter of Drug Absorption and Transport, Department of Biopharmacy and Pharmaceutical Technology, Institute of Pharmacy, University of Greifswald, 17489 Greifswald, GermanyClinic for Dental Prosthetics and Biomedical Materials Science, Hanover Medical School, 30625 Hannover, GermanyClinic for Dental Prosthetics and Biomedical Materials Science, Hanover Medical School, 30625 Hannover, GermanyDepartment of Otorhinolaryngology, Head and Neck Surgery, Lower Saxony Center for Biomedical Engineering, Implant Research and Development (NIFE), Hannover Medical School, Stadtfelddamm 34, 30625 Hannover, GermanyDepartment of Otorhinolaryngology, Head and Neck Surgery, Lower Saxony Center for Biomedical Engineering, Implant Research and Development (NIFE), Hannover Medical School, Stadtfelddamm 34, 30625 Hannover, GermanyPostoperative restenosis in patients with external ear canal (EEC) atresia or stenosis is a common complication following canaloplasty. Our aim in this study was to explore the feasibility of using a three dimensionally (3D)-printed, patient-individualized, drug ((dexamethasone (DEX)), and ciprofloxacin (cipro))-releasing external ear canal implant (EECI) as a postoperative stent after canaloplasty. We designed and pre-clinically tested this novel implant for drug release (by high-performance liquid chromatography), biocompatibility (by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay), bio-efficacy (by the TNF-α (tumor necrosis factor-alpha)-reduction test (DEX) and inhibition zone test (for cipro)), and microbial contamination (formation of turbidity or sediments in culture medium). The EECI was implanted for the first time to one patient with a history of congenital EEC atresia and state after three canaloplasties due to EEC restenosis. The preclinical tests revealed no cytotoxic effect of the used materials; an antibacterial effect was verified against the bacteria <i>Staphylococcus aureus</i> and <i>Pseudomonas aeruginosa</i>, and the tested UV-irradiated EECI showed no microbiological contamination. Based on the test results, the combination of silicone with 1% DEX and 0.3% cipro was chosen to treat the patient. The EECI was implantable into the EEC; the postoperative follow-up visits revealed no otogenic symptoms or infections and the EECI was explanted three months postoperatively. Even at 12 months postoperatively, the EEC showed good epithelialization and patency. Here, we report the first ever clinical application of an individualized, drug-releasing, mechanically flexible implant and suggest that our novel EECI represents a safe and effective method for postoperatively stenting the reconstructed EEC.https://www.mdpi.com/1999-4923/14/6/1242ear canal stenosispersonalized implantdrug-eluting implantadditive manufacturingpreoperative workflowexternal auditory canal |
| spellingShingle | Farnaz Matin-Mann Ziwen Gao Jana Schwieger Martin Ulbricht Vanessa Domsta Stefan Senekowitsch Werner Weitschies Anne Seidlitz Katharina Doll Meike Stiesch Thomas Lenarz Verena Scheper Individualized, Additively Manufactured Drug-Releasing External Ear Canal Implant for Prevention of Postoperative Restenosis: Development, In Vitro Testing, and Proof of Concept in an Individual Curative Trial Pharmaceutics ear canal stenosis personalized implant drug-eluting implant additive manufacturing preoperative workflow external auditory canal |
| title | Individualized, Additively Manufactured Drug-Releasing External Ear Canal Implant for Prevention of Postoperative Restenosis: Development, In Vitro Testing, and Proof of Concept in an Individual Curative Trial |
| title_full | Individualized, Additively Manufactured Drug-Releasing External Ear Canal Implant for Prevention of Postoperative Restenosis: Development, In Vitro Testing, and Proof of Concept in an Individual Curative Trial |
| title_fullStr | Individualized, Additively Manufactured Drug-Releasing External Ear Canal Implant for Prevention of Postoperative Restenosis: Development, In Vitro Testing, and Proof of Concept in an Individual Curative Trial |
| title_full_unstemmed | Individualized, Additively Manufactured Drug-Releasing External Ear Canal Implant for Prevention of Postoperative Restenosis: Development, In Vitro Testing, and Proof of Concept in an Individual Curative Trial |
| title_short | Individualized, Additively Manufactured Drug-Releasing External Ear Canal Implant for Prevention of Postoperative Restenosis: Development, In Vitro Testing, and Proof of Concept in an Individual Curative Trial |
| title_sort | individualized additively manufactured drug releasing external ear canal implant for prevention of postoperative restenosis development in vitro testing and proof of concept in an individual curative trial |
| topic | ear canal stenosis personalized implant drug-eluting implant additive manufacturing preoperative workflow external auditory canal |
| url | https://www.mdpi.com/1999-4923/14/6/1242 |
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