Preclinical assessment of clinically streamlined, 3D-printed, biocompatible single- and two-stage tissue scaffolds for ear reconstruction.

Julia R Brennan, Ashley Cornett, Brian Chang, Sarah J Crotts, Zahra Nourmohammadi, Isabelle Lombaert, Scott J Hollister, David A Zopf
Author Information
  1. Julia R Brennan: Department of Otolaryngology-Head and Neck Surgery, University of Michigan, Ann Arbor, Michigan, USA.
  2. Ashley Cornett: Department of Biologic and Materials Sciences & Prosthodontics, School of Dentistry, University of Michigan, Ann Arbor, Michigan, USA.
  3. Brian Chang: Department of Pediatrics, UCLA Mattel Children's Hospital, Los Angeles, California, USA. ORCID
  4. Sarah J Crotts: Center for 3D Medical Fabrication, Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, Georgia, USA.
  5. Zahra Nourmohammadi: Department of Otolaryngology-Head and Neck Surgery, University of Michigan, Ann Arbor, Michigan, USA.
  6. Isabelle Lombaert: Department of Biologic and Materials Sciences & Prosthodontics, School of Dentistry, University of Michigan, Ann Arbor, Michigan, USA.
  7. Scott J Hollister: Center for 3D Medical Fabrication, Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, Georgia, USA.
  8. David A Zopf: Department of Otolaryngology-Head and Neck Surgery, University of Michigan, Ann Arbor, Michigan, USA.

Abstract

Auricular reconstruction is a technically demanding procedure requiring significant surgical expertise, as the current gold standard involves hand carving of the costal cartilage into an auricular framework and re-implantation of the tissue. 3D-printing presents a powerful tool that can reduce technical demands associated with the procedure. Our group compared clinical, radiological, histological, and biomechanical outcomes in single- and two-stage 3D-printed auricular tissue scaffolds in an athymic rodent model. Briefly, an external anatomic envelope of a human auricle was created using DICOM computed tomography (CT) images and modified in design to create a two-stage, lock-in-key base and elevating platform. Single- and two-stage scaffolds were 3D-printed by laser sintering poly-L-caprolactone (PCL) then implanted subcutaneously in five athymic rats each. Rats were monitored for ulcer formation, site infection, and scaffold distortion weekly, and scaffolds were explanted at 8 weeks with analysis using microCT and histologic staining. Nonlinear finite element analysis was performed to determine areas of high strain in relation to ulcer formation. Scaffolds demonstrated precise anatomic appearance and maintenance of integrity of both anterior and posterior auricular surfaces and scaffold projection, with no statistically significant differences in complications noted between the single- and two-staged implantation. While minor superficial ulcers occurred most commonly at the lateral and superior helix coincident with finite element predictions of high skin strains, evidence of robust tissue ingrowth and angiogenesis was visible grossly and histologically. This promising preclinical small animal model supports future initiatives for making clinically viable options for an ear tissue scaffold.

Keywords

References

  1. J Biomech Eng. 2005 Oct;127(5):838-48 [PMID: 16248314]
  2. Laryngoscope. 2004 May;114(5):867-70 [PMID: 15126746]
  3. Plast Reconstr Surg. 1995 May;95(6):961-8 [PMID: 7732143]
  4. Plast Reconstr Surg. 1993 Aug;92(2):187-201 [PMID: 8337267]
  5. J Plast Reconstr Aesthet Surg. 2015 Aug;68(8):1085-94 [PMID: 26026221]
  6. Cleft Palate Craniofac J. 1992 Nov;29(6):578-84; discussion 570 [PMID: 1450200]
  7. Tissue Eng Part C Methods. 2017 Mar;23(3):136-145 [PMID: 28093047]
  8. J Biomech Eng. 2012 Jan;134(1):011005 [PMID: 22482660]
  9. Laryngoscope. 2015 Aug;125(8):E262-8 [PMID: 25891012]
  10. Tissue Eng Part B Rev. 2012 Feb;18(1):51-61 [PMID: 21827281]
  11. Int J Pediatr Otorhinolaryngol. 2018 Nov;114:170-174 [PMID: 30262359]
  12. Nat Mater. 2005 Jul;4(7):518-24 [PMID: 16003400]
  13. N Engl J Med. 2013 May 23;368(21):2043-5 [PMID: 23697530]
  14. Laryngoscope. 2019 Aug;129(8):1763-1771 [PMID: 30794335]
  15. Mol Biotechnol. 2018 Jul;60(7):506-532 [PMID: 29761314]
  16. Acta Biomater. 2011 Feb;7(2):505-14 [PMID: 20807597]
  17. Tissue Eng Part A. 2011 Jul;17(13-14):1831-9 [PMID: 21395465]
  18. Plast Reconstr Surg. 2009 Jul;124(1 Suppl):14e-26e [PMID: 19568136]
  19. JAMA Facial Plast Surg. 2014 Jul-Aug;16(4):240-4 [PMID: 24763669]
  20. Orthod Craniofac Res. 2005 Aug;8(3):162-73 [PMID: 16022718]
  21. Otolaryngol Head Neck Surg. 2015 Jan;152(1):57-62 [PMID: 25281749]
  22. Facial Plast Surg. 2012 Jun;28(3):333-9 [PMID: 22723235]
  23. Annu Rev Biomed Eng. 2017 Jun 21;19:279-299 [PMID: 28633565]

Grants

  1. R01 DE027034/NIDCR NIH HHS
  2. T32 DC005356/NIH HHS
  3. TL1 TR002242/NCATS NIH HHS
  4. T32 DC005356/NIDCD NIH HHS

MeSH Term

Animals
Chondrocytes
Ear Cartilage
Printing, Three-Dimensional
Rats
Rats, Nude
Plastic Surgery Procedures
Tissue Engineering
Tissue Scaffolds

Word Cloud

Created with Highcharts 10.0.0tissueauriculartwo-stagescaffoldsreconstructionsingle-3D-printedscaffoldanalysisfiniteelementproceduresignificant3D-printingathymicmodelanatomicusingulcerformationhighclinicallyearAuriculartechnicallydemandingrequiringsurgicalexpertisecurrentgoldstandardinvolveshandcarvingcostalcartilageframeworkre-implantationpresentspowerfultoolcanreducetechnicaldemandsassociatedgroupcomparedclinicalradiologicalhistologicalbiomechanicaloutcomesrodentBrieflyexternalenvelopehumanauriclecreatedDICOMcomputedtomographyCTimagesmodifieddesigncreatelock-in-keybaseelevatingplatformSingle-lasersinteringpoly-L-caprolactonePCLimplantedsubcutaneouslyfiveratsRatsmonitoredsiteinfectiondistortionweeklyexplanted8 weeksmicroCThistologicstainingNonlinearperformeddetermineareasstrainrelationScaffoldsdemonstratedpreciseappearancemaintenanceintegrityanteriorposteriorsurfacesprojectionstatisticallydifferencescomplicationsnotedtwo-stagedimplantationminorsuperficialulcersoccurredcommonlylateralsuperiorhelixcoincidentpredictionsskinstrainsevidencerobustingrowthangiogenesisvisiblegrosslyhistologicallypromisingpreclinicalsmallanimalsupportsfutureinitiativesmakingviableoptionsPreclinicalassessmentstreamlinedbiocompatiblebioscaffoldsnonlinear

Similar Articles

Cited By