Tympanic membrane (TM) perforations are common, with current treatments for chronic perforations involving surgery, using various graft materials, from autologous cartilage or fascia through to paper patch. Recent research developments in this field have begun applying the principles of tissue engineering, with appropriate scaffolds, cells, and bioactive molecules (BMs). This has revolutionized the therapeutic approach due to the availability of a wide range of materials with appropriate compatibility and mechanical properties to regenerate the membrane acoustics and may also represent a paradigm shift in the management of TM perforations in an outpatient setting without surgery. However, many factors need to be considered in the fabrication of a bioengineered TM. This review discusses the issues associated with current treatment and examines TM wound healing relevant to the construction of a bioengineered TM. It also describes the tissue-engineering approach to TM regeneration by summarizing currently used scaffolds, BMs, and cells in TM wound healing. Finally, it considers the design of scaffolds, delivery of BMs, and cell engraftment toward potential clinical application.

Pulmonary infections by Sporothrix spp. manifest radiologically as cavitary or non-cavitary disease depending on whether the infection is primary pulmonary or multifocal sporotrichosis. Despite current guidelines, the optimal management for pulmonary sporotrichosis remains unclear. In order to clarify this, we present two cases of pulmonary sporotrichosis, as well as the results of a comprehensive literature review of treatment outcomes based on clinico-radiological presentation patterns of the disease. A literature search of all case reports in English language over the last 50 years (1960-2010) was conducted. Data on patient characteristics, risk factors, clinico-radiological patterns, treatment modalities and outcomes were collected and analyzed. A total of 86 cases were identified, i.e., 64 (74.4%) primary pulmonary and 22 (25.6%) multifocal sporotrichosis. Radiologically, primary pulmonary disease was commonly characterized by cavity formation which was lacking in multifocal infections (P = 0.0001). Immunosuppressant use was more common in multifocal sporotrichosis (P = 0.0001), while hemoptysis was more common in primary pulmonary form (P = 0.01). No other differences in patient characteristics or risk factors were noted. Extra-pulmonary multifocal sporotrichosis most commonly involved skin (81.8%) and joints (45.4%). For patients with cavitary primary pulmonary sporotrichosis, outcomes from medical therapy alone were inferior to surgical intervention (P = 0.02). However, for both primary pulmonary and multifocal sporotrichosis with non-cavitary disease, medical therapy alone provided good outcomes. Only 12 (16.7%) cases were treated with itraconazole. Treatment of pulmonary sporotrichosis should be guided by the clinico-radiological patterns of presentation. Medical therapy alone is likely sufficient for non-cavitary disease while early surgery should be considered for cavitary primary pulmonary sporotrichosis. The experience in treating cavitary disease with itraconazole alone is limited and further data are required.

Tympanic membrane (TM) perforations lead to significant hearing loss and result in possible infection of the middle ear. Myringoplasty is commonly performed to repair chronic perforations. Although various grafts and materials have been used to promote TM regeneration, all have associated limitations. The aim of this study was to evaluate the efficacy and feasibility of two graft materials, silk fibroin scaffold (SFS) and porcine-derived acellular collagen type I/III scaffold (ACS), compared with two commonly used graft materials (paper patch and Gelfoam) for the promotion of TM regeneration. These scaffolds were implanted using on-lay myringoplasty in an acute TM perforation rat model. Surface morphology of the scaffolds was observed with scanning electron microscopy. The morphology of the TM was assessed at various time points postimplantation using otoscopy, light and electron microscopy, and functional outcomes by auditory brainstem responses. We found that SFS and ACS significantly accelerated the TM perforation closure, obtained optimal TM thickness, and resulted in better trilaminar morphology with well-organized collagen fibers and early restoration of hearing. However, paper patch and Gelfoam lost their scaffold function in the early stages and showed an inflammatory response, which may have contributed to delayed healing. This study indicates that compared with paper patch and Gelfoam, SFS and ACS are more effective in promoting an early TM regeneration and an improved hearing, suggesting that these scaffolds may be potential substitutes for clinical use.