Repair of Tympanic Membrane Perforations with Customized, Bioprinted Ear Grafts Using Chinchilla Models.

MedStar author(s):
Citation: Tissue engineering. Part A.. 24(5-6):527-535, 2018 03.PMID: 28726587Institution: MedStar Health Research InstituteForm of publication: Journal ArticleMedline article type(s): Journal ArticleSubject headings: *Bioprinting | *Gelatin/ch [Chemistry] | *Implants, Experimental | *Tympanic Membrane Perforation/th [Therapy] | *Tympanic Membrane/me [Metabolism] | Animals | Disease Models, Animal | Female | Mice | NIH 3T3 Cells | Tympanic Membrane Perforation/me [Metabolism] | Tympanic Membrane Perforation/pa [Pathology] | Tympanic Membrane/pa [Pathology]Year: 2018ISSN:
  • 1937-3341
Name of journal: Tissue engineering. Part AAbstract: The goal of this work is to develop an innovative method that combines bioprinting and endoscopic imaging to repair tympanic membrane perforations (TMPs). TMPs are a serious health issue because they can lead to both conductive hearing loss and repeated otitis media. TMPs occur in 3 to 5% of cases after ear tube placement as well as in cases of acute otitis media (the second most common infection in pediatrics), chronic otitis media with or without cholesteatoma, or as a result of barotrauma to the ear. About 55,000 tympanoplasties, the surgery performed to reconstruct TMPs, are performed every year and the commonly used cartilage grafting technique has a success rate between 43% to 100%. This wide variability in successful tympanoplasty indicates that the current approach relies heavily on the skill of the surgeon to carve the shield graft into the shape of the TMP, which can be extremely difficult because of the perforation's irregular shape. To this end, we hypothesized that patient specific acellular grafts can be bioprinted to repair TMPs. In vitro data demonstrated our approach resulted in excellent wound healing responses (e.g. cell invasion and proliferations) using our bioprinted gelatin methacrylate constructs. Based on these results, we then bioprinted customized acellular grafts to treat TMP based on endoscopic imaging of the perforation and demonstrated improved TMP healing in a chinchilla study. These ear graft techniques could transform clinical practice by eliminating the need for hand-carved grafts. To our knowledge, this is the first proof-of-concept of using bioprinting and endoscopic imaging to fabricate customized grafts to treat tissue perforations. This technology could be transferred to other medical pathologies and be employed to rapidly scan internal organs such as intestines for microperforations, brain covering (Dura mater) for determination of sites of potential Cerebrospinal Fluid (CSF) leaks, and vascular systems to determine arterial wall damage prior to aneurysm rupture in strokes.All authors: Cleary K, Fisher JP, Fuson A, Gandhi N, Jenkins A, Kuo CY, Monfaredi R, Reilly B, Romero M, Santoro M, Wilson EFiscal year: FY2018Digital Object Identifier: Date added to catalog: 2017-07-24
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Journal Article MedStar Authors Catalog Article 28726587 Available 28726587

The goal of this work is to develop an innovative method that combines bioprinting and endoscopic imaging to repair tympanic membrane perforations (TMPs). TMPs are a serious health issue because they can lead to both conductive hearing loss and repeated otitis media. TMPs occur in 3 to 5% of cases after ear tube placement as well as in cases of acute otitis media (the second most common infection in pediatrics), chronic otitis media with or without cholesteatoma, or as a result of barotrauma to the ear. About 55,000 tympanoplasties, the surgery performed to reconstruct TMPs, are performed every year and the commonly used cartilage grafting technique has a success rate between 43% to 100%. This wide variability in successful tympanoplasty indicates that the current approach relies heavily on the skill of the surgeon to carve the shield graft into the shape of the TMP, which can be extremely difficult because of the perforation's irregular shape. To this end, we hypothesized that patient specific acellular grafts can be bioprinted to repair TMPs. In vitro data demonstrated our approach resulted in excellent wound healing responses (e.g. cell invasion and proliferations) using our bioprinted gelatin methacrylate constructs. Based on these results, we then bioprinted customized acellular grafts to treat TMP based on endoscopic imaging of the perforation and demonstrated improved TMP healing in a chinchilla study. These ear graft techniques could transform clinical practice by eliminating the need for hand-carved grafts. To our knowledge, this is the first proof-of-concept of using bioprinting and endoscopic imaging to fabricate customized grafts to treat tissue perforations. This technology could be transferred to other medical pathologies and be employed to rapidly scan internal organs such as intestines for microperforations, brain covering (Dura mater) for determination of sites of potential Cerebrospinal Fluid (CSF) leaks, and vascular systems to determine arterial wall damage prior to aneurysm rupture in strokes.

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