Three-Dimensional-Printed GelMA-KerMA Composite Patches as an Innovative Platform for Potential Tissue Engineering of Tympanic Membrane Perforations

Author:

Bedir Tuba12,Baykara Dilruba12,Yildirim Ridvan12ORCID,Calikoglu Koyuncu Ayse Ceren12,Sahin Ali3ORCID,Kaya Elif4ORCID,Tinaz Gulgun Bosgelmez4ORCID,Insel Mert Akin5ORCID,Topuzogulları Murat6ORCID,Gunduz Oguzhan127,Ustundag Cem Bulent67,Narayan Roger8ORCID

Affiliation:

1. Center for Nanotechnology and Biomaterials Application and Research (NBUAM), Marmara University, Istanbul 34722, Turkey

2. Department of Metallurgical and Materials Engineering, Faculty of Technology, Marmara University, Istanbul 34722, Turkey

3. Department of Biochemistry, Faculty of Medicine, Marmara University, Istanbul 34722, Turkey

4. Department of Basic Pharmaceutical Sciences, Faculty of Pharmacy, Marmara University, Istanbul 34668, Turkey

5. Department of Chemical Engineering, Faculty of Chemical and Metallurgical Engineering, Yildiz Technical University, Istanbul 34210, Turkey

6. Department of Bioengineering, Faculty of Chemical and Metallurgical Engineering, Yildiz Technical University, Istanbul 34210, Turkey

7. Health Biotechnology Joint Research and Application Center of Excellence, Istanbul 34220, Turkey

8. Joint Department of Biomedical Engineering, University of North Carolina, Chapel Hill, NC 27599, USA

Abstract

Tympanic membrane (TM) perforations, primarily induced by middle ear infections, the introduction of foreign objects into the ear, and acoustic trauma, lead to hearing abnormalities and ear infections. We describe the design and fabrication of a novel composite patch containing photocrosslinkable gelatin methacryloyl (GelMA) and keratin methacryloyl (KerMA) hydrogels. GelMA-KerMA patches containing conical microneedles in their design were developed using the digital light processing (DLP) 3D printing approach. Following this, the patches were biofunctionalized by applying a coaxial coating with PVA nanoparticles loaded with gentamicin (GEN) and fibroblast growth factor (FGF-2) with the Electrohydrodynamic Atomization (EHDA) method. The developed nanoparticle-coated 3D-printed patches were evaluated in terms of their chemical, morphological, mechanical, swelling, and degradation behavior. In addition, the GEN and FGF-2 release profiles, antimicrobial properties, and biocompatibility of the patches were examined in vitro. The morphological assessment verified the successful fabrication and nanoparticle coating of the 3D-printed GelMA-KerMA patches. The outcomes of antibacterial tests demonstrated that GEN@PVA/GelMA-KerMA patches exhibited substantial antibacterial efficacy against Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli. Furthermore, cell culture studies revealed that GelMA-KerMA patches were biocompatible with human adipose-derived mesenchymal stem cells (hADMSC) and supported cell attachment and proliferation without any cytotoxicity. These findings indicated that biofunctional 3D-printed GelMA-KerMA patches have the potential to be a promising therapeutic approach for addressing TM perforations.

Funder

Turkish Scientific and Technical Research Council (TUBITAK) 1001 Project—Tympatch

Marmara University Scientific Research Committee

Publisher

MDPI AG

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