A Healing Method of Tympanic Membrane Perforations Using Three-Dimensional Porous Chitosan Scaffolds

Abstract

Both surgical tympanoplasty and paper patch grafts are frequently procedured to heal tympanic membrane (TM) perforation or chronic otitis media, despite their many disadvantages. In this study, we report a new healing method of TM perforation by using three-dimensional (3D) porous chitosan scaffolds (3D chitosan scaffolds) as an alternative method to surgical treatment or paper patch graft. Various 3D chitosan scaffolds were prepared; and the structural characteristics, mechanical property, in vitro biocompatibility, and healing effects of the 3D chitosan scaffolds as an artificial TM in in vivo animal studies were investigated. A 3D chitosan scaffold of 5 wt.% chitosan concentration showed good proliferation of TM cells in an in vitro study, as well as suitable structural characteristics and mechanical property, as compared with either 1% or 3% chitosan. In in vivo animal studies, 3D chitosan scaffold were able to migrate through the pores and surfaces of TM cells, thus leading to more effective TM regeneration than paper patch technique. Histological observations demonstrated that the regenerated TM with the 3D chitosan scaffold consisted of three (epidermal, connective tissue, and mucosal) layers and were thicker than normal TMs. The 3D chitosan scaffold technique may be an optimal healing method used in lieu of surgical tympanoplasty in certain cases to heal perforated TMs.

Regeneration of chronic tympanic membrane perforation using 3D collagen with topical umbilical cord serum

“…In general, the 3D scaffolds should play the role of the extracellular matrix (ECM); as a result, they need various biological and physical properties to obtain successful tissue regeneration [25,26]. In the TM regeneration, 3D scaffold has been rarely used, only Kim et al [10] used 3D chitosan scaffolds for the first time. The 3D chistosan scaffolds showed good TM cell viability in vitro with acceleration TM regeneration in vivo.…”

“…However, it is difficult to treat a chronic TM perforation due to decreased regenerative activity of the TM at the margin of the perforation. In an effort to overcome this drawback, the use of the novel adjuvant scaffolds such as collagen [5], calcium alginate [6], silk [7], and chitosan [8][9][10][11] have been tried as patch. However, only bioscaffold showed a limited rate of healing in a chronic TM perforation study, similar to the rate of the paper patch technique.…”

Bacterial Cellulose Nanofibrillar Patch as a Wound Healing Platform of Tympanic Membrane Perforation

“…The tympanic membrane (TM) is composed of 3 tissue layers, including the epidermal, connective, and mucosal layers, and TM regeneration is representative of the typical wound healing procedure 15, 16. Traumatic TM perforation, caused by physical external factors or insults to the middle ear, is a very common clinical problem worldwide, which may present with conductive healing loss and chronic perforations 16–19. In such cases, the TM is typically regenerated spontaneously.…”

“…Additionally, TM perforations that are large are combined with chronic otorrhea or inflammation cannot undergo spontaneous TM regeneration 16. The paper patch graft technique has been frequently used to heal traumatic TM perforations in outpatient department clinics to overcome the limitations of spontaneous TM regeneration; the paper patch guides the growth and migration of TM cells to the patch from the borders of the perforation, which can lead to TM regeneration more quickly than in spontaneous TM regeneration 16–19. However, the paper patch has several disadvantages, such as nonbiocompatibility, nontransparency, and nonflexibility, as well as ease of detachment and nonresistance to infection 16.…”

Tissue Engineering of the Tympanic Membrane

“…55 Chitosan confers antibacterial properties and has been shown to promote wound healing of skin, bone, and liver, 56 and threedimensional chitosan was found to integrate into the regenerated TM when placed using inlay myringoplasty. 57 On the other hand, alginate, a natural organic polymer derived from seaweed, has improved ease of handling when crosslinked with calcium. Calcium alginate grafts act as a scaffold for medial and lateral growth of mucosal and keratinized epithelium.…”