title: Regeneration of chronic tympanic membrane perforation using 3D collagen with topical umbilical cord serum.
abstract: Chronic tympanic membrane (TM) perforation is one of the most common otology complications. Current surgical management of TM perforation includes myringoplasty and tympanoplasty. The purpose of this study was to evaluate the efficacy and feasibility of three dimensional (3D) porous collagen scaffolds with topically applied human umbilical cord serum (UCS) for the regeneration of chronic TM perforation in guinea pigs. To achieve this goal, we fabricated porous 3D collagen scaffolds (avg. strut diameter of 236 ± 51 μm, avg. pore size of 382 ± 67 μm, and a porosity of 96%) by using a 3 axis robot dispensing and low temperature plate systems. Guinea pigs were used in a model of chronic TM perforation. In the experimental group (n=10), 3D collagen scaffold was placed on the perforation and topically applied of UCS every other day for a period of 8 days. The control group ears (n=10) were treated with paper discs and phosphate buffered saline (PBS) only using the same regimen. 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. 43% of the control group, and this difference was statistically significant (p=0.034). The ABR threshold at all frequencies of the experimental group was significantly 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 is very small and they are not statistically significant below 1 kHz (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 absence of fibrous layer like a dimeric TM.
authors.affiliation: Department of Otolaryngology, Chonnam National University Medical School, Gwangju, South Korea; Research Center for Resistant Cells, Chosun Medical School, Gwangju, South Korea.
authors.forename: Chul Ho
authors.initials: CH
authors.lastname: Jang
authors.forename: Yong Beom
authors.initials: YB
authors.lastname: Cho
authors.forename: MyungGu
authors.initials: M
authors.lastname: Yeo
authors.forename: Hyeongjin
authors.initials: H
authors.lastname: Lee
authors.forename: Eun Jung
authors.initials: EJ
authors.lastname: Min
authors.forename: Byung Hhwa
authors.initials: BH
authors.lastname: Lee
authors.forename: Geun Hyung
authors.initials: GH
authors.lastname: Kim
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D002470:Cell Survival / Q000187:drug effects; D003094:Collagen / Q000378:metabolism* / Q000494:pharmacology*; D005240:Feasibility Studies; D005786:Gene Expression Regulation / Q000187:drug effects; D006168:Guinea Pigs; D006309:Hearing / Q000187:drug effects; D006801:Humans; D016062:Porosity; D020127:Recovery of Function / Q000187:drug effects; D012038:Regeneration / Q000187:drug effects*; D044967:Serum / Q000378:metabolism*; D013696:Temperature; D054457:Tissue Scaffolds; D014432:Tympanic Membrane / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D018058:Tympanic Membrane Perforation / Q000503:physiopathology*; D014470:Umbilical Cord / Q000098:blood supply*; D014732:Vibration
chemical_list: D003094:Collagen
keywords: 3D collagen scaffold; Tissue regeneration; Tympanic membrane; Umbilical cord serum