title: Mesenchymal stem cell-laden hybrid scaffold for regenerating subacute tympanic membrane perforation.
abstract: Tympanic membrane (TM) perforation is one of the most common otology complications. To date, there has not been reported TM regeneration using bioprinted scaffold. The purpose of this study was to evaluate the efficacy and feasibility of bioprinted polycaprolactone/collagen/alginate-mesenchymal stem cell (PCAMSC) scaffolds for the regeneration of subacute TM perforation. Sprague-Dawley rats were used in an animal model of subacute TM perforation. In the experimental group (n=7), bioprinted 3D PCAMSC scaffold was placed on the perforation. The control group (n=7) were treated with polycaprolactone/collagen/alginate (PCA) scaffold. Healing time, acoustic-mechanical properties, and morphological analysis were performed by otoendoscopy, auditory brainstem response (ABR), single-point laser doppler vibrometer (LDV), optical coherence tomography (OCT), and light microscopic evaluation. The closure of the TM perforation was achieved in 100% of the experimental group vs. 72% of the control group, and this difference was statistically significant (p<0.05). The ABR threshold at all frequencies of the experimental group was recovered to the normal level compared to the control group. TM vibration velocity in the experimental group recovered similar to the normal control level. The difference are very small and they are not statistically significant below 1kHz (p=0.074). By OCT and light microscopic examination, regenerated TM of the experimental group showed thickened fibrous and mucosal layer. In contrast, the control group showed well regenerated but less thickened than experimental group. From these results, the cell-laden PCAMSC scaffold offers a significant advantage in the TM regeneration in a rat subacute TM perforation model. It may offer attractive opportunities in the conservative clinical treatment.
authors.affiliation: Department of Otolaryngology, Chonnam National University Medical School, Gwangju, South Korea. Electronic address: chulsavio@hanmail.net.
authors.forename: Chul Ho
authors.initials: CH
authors.lastname: Jang
authors.affiliation: Department of Biomechatronic Engineering, College of Biotechnology and Bioengineering, Sungkyunkwan University, Suwon, South Korea.
authors.forename: SeungHyun
authors.initials: S
authors.lastname: Ahn
authors.affiliation: School of Information and Communications, Gwangju Institute of Science and Technology, Gwangju, South Korea.
authors.forename: Jae Whi
authors.initials: JW
authors.lastname: Lee
authors.affiliation: School of Information and Communications, Gwangju Institute of Science and Technology, Gwangju, South Korea.
authors.forename: Byeong Ha
authors.initials: BH
authors.lastname: Lee
authors.affiliation: Department of Biomechatronic Engineering, College of Biotechnology and Bioengineering, Sungkyunkwan University, Suwon, South Korea.
authors.forename: Hyeongjin
authors.initials: H
authors.lastname: Lee
authors.affiliation: Department of Biomechatronic Engineering, College of Biotechnology and Bioengineering, Sungkyunkwan University, Suwon, South Korea. Electronic address: gkimbme@skku.edu.
authors.forename: GeunHyung
authors.initials: G
authors.lastname: Kim
mesh_terms: D000464:Alginates / Q000737:chemistry; D000818:Animals; D001299:Audiometry; D003094:Collagen / Q000737:chemistry; D004195:Disease Models, Animal; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism; D018613:Microscopy, Confocal; D011091:Polyesters / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D012038:Regeneration; D013718:Tensile Strength; D054457:Tissue Scaffolds / Q000737:chemistry*; D041623:Tomography, Optical Coherence; D018058:Tympanic Membrane Perforation / Q000000981:diagnostic imaging / Q000503:physiopathology / Q000628:therapy*
chemical_list: D000464:Alginates; D006603:Hexuronic Acids; D011091:Polyesters; C016240:polycaprolactone; D020723:Glucuronic Acid; D003094:Collagen
keywords: MSCs-laden structure; Scaffold; Tympanic membrane