Application of mesenchymal stem cell for tympanic membrane regeneration by tissue engineering approach

Regeneration is a biological process of cell renewal that takes place in damaged tissues or organs. It is naturally stimulated by the release of different growth factors, cytokines, surface molecules, and stem cells at the wounded sites. The tympanic membrane (TM) is an essential component of the hearing process in the auditory system, which can amplify and transmit sound vibrations through a chain of mobile ossicles. Middle ear infection, external sound pressure, insertion of sharp objects into the ear, and severe trauma are the main causes of TM perforations (TMPs), which could result in deficient hearing function. So far, otolaryngologists have employed surgical procedures (myringoplasty or tympanoplasty) to close the perforated eardrum. Because of limitations such as side effects, discomfort, and high cost to patients, there is a need for better alternatives to surgical procedures. Tissue engineering is a promising tool that can overcome the operational risk and restore, maintain, and improve the function of the TM using a range of biocompatible scaffolds, commercially available growth factors, and stem cells. Currently, multipotent mesenchymal stem cells (MSCs) are a good therapeutic option for the treatment of TMPs because of their self-renewing, and autocrine and paracrine activities. As there are fewer risks of isolation in the use of MSCs for the treatment of TMPs, they are more advantageous for tissue regeneration. The delivery of either MSCs alone or a combination of MSCs with biomaterials and growth factors (GFs) at the ruptured TM sites may enhance the activation of epithelial stem cell markers and increase the migration and proliferation of keratinocytes resulting in faster closure of TMPs. This review focuses on the current strategies used to treat TMPs and the importance of MSCs in TM regeneration. Particularly, we have discussed the synergistic effect of MSCs and scaffolds or GFs or scaffolds/GFs in TM regeneration. Finally, with the advancement of tissue engineering technologies such as 3D and 4D bioprinting, MSCs can be used to design patient-specific scaffolds, which may contain physical and chemical guidance cues to improve the extent and rate of targeted tissue regeneration.