TM wound healing contrasts with cutaneous wound healing in that keratinocytes are the first cells to close the wound and not the last. A keratin scaffold may not be important in the healing process. The malleus plays a crucial role in the healing of the TM and is the site of significant mitotic activity during the healing process. Migration across layers of the TM appears to account for the closure of the perforation.

Preimplantation embryos generate intercellular junctions during differentiation of the trophectoderm epithelium and the formation of the blastocyst. These membrane complexes comprise gap junctions, adherens junctions, tight junctions, and desmosomes, each performing fundamental roles in cellular communication, adhesion, and differentiation. The mouse embryo has been used as a model for the biogenesis of cell junctions. Their construction is achieved by temporally regulated gene expression programs. Mechanisms of junction membrane assembly include the timing of transcription, translation, and post-translational modifications of specific junctional proteins. Human embryos exhibit similar expression programs, and defects in these programs may contribute to reduced embryo viability.

Developments in the treatment of chronic tympanic membrane perforation have been hindered by the lack of an ideal animal model. It is not appropriate to test such treatments on acute perforations as the majority of these heal spontaneously. An ideal animal model would be one that most closely resembles the human clinical situation. It should be inexpensive, readily available, and easy to create. There have been a number of attempts to create a chronic tympanic membrane perforation model with limited success. All published attempts at chronic tympanic membrane perforations have been reviewed and the limitations of each model are discussed. A number of areas for research exist for further developing a chronic tympanic membrane perforation model. These areas include a perforation model in the presence of bacteria and eustachian tube dysfunction. Understanding the molecular and genetic mechanisms of chronic otitis media and potential treatments will also be useful.

Human tympanic membrane cells (hTMCs), harvested from tympanic membrane (TM) explants, were grown in culture and then seeded on membranes prepared from silkworm (Bombyx mori) silk fibroin (BMSF) and on tissue-culture plastic membranes (PET). Fibroin was isolated from silk cast into membranes with a thickness of 10-15 microm. The hTMCs were cultured on both materials for 15 days in a serum-containing culture medium. The cells grown on both substrata were subjected to nuclear staining (DAPI) and counted. Further, the cultures were immunostained for a number of protein markers related to the epithelial/keratinocyte phenotype and cell adhesion complexes. The BMSF membranes supported levels of hTMC growth higher than that observed on the PET membranes. The immunofluorochemical analysis indicated unequivocally that BMSF is a more suitable substratum than PET with respect to the growth patterns, proliferation, and cell-cell contact and adhesion. BMSF appear as a promising substratum in the tissue-engineered constructs for the replacement of TM in case of nonhealing perforations.