Overview of Tracheal Tissue Engineering: Clinical Need Drives the Laboratory Approach

Abstract

Breathing is a natural function that most of us do not even think about, but for those who suffer from disease or damage of the trachea, the obstruction of breathing can mean severe restrictions to quality of life or may even be fatal. Replacement and reconstruction of the trachea is one of the most difficult procedures in otolaryngology/head and neck surgery, and also one of the most vital. Previous reviews have focused primarily on clinical perspectives or instead on engineering strategies. However, the current review endeavors to bridge this gap by evaluating engineering approaches in a practical clinical context. For example, although contemporary approaches often include in vitro bioreactor pre-culture, or sub-cutaneous in vivo conditioning, the limitations they present in terms of regulatory approval, cost, additional surgery, and/or risk of infection challenge engineers to develop the next generation of biodegradable/resorbable biomaterials that can be directly implanted in situ. Essentially, the functionality of the replacement is the most important requirement. It must be the correct shape and size, achieve an airtight fit, resist collapse as it is replaced by new tissue, and be non-immunogenic. As we look to the future, there will be no one-size-fits-all solution.

Engineering Functional Epithelium for Regenerative Medicine and In Vitro Organ Models: A Review

“…84 In some cases, such defects can be resolved by end to end anastomosis if the length of the defect is less than 5 cm. 85 However, when the size of the defect is larger than this limit, the implants or the tissue engineered structures become a necessity. To this end, allografts and a wide range of biomaterials have been used for replacing tracheal defects.…”

“…87 The methods used in trachea tissue engineering are (1) utilization of decellularized matrices using allogenic trachea or other tubular organs (e.g., the human aorta, which has been successfully implanted for replacement of bronchus), 89 (2) scaffold systems based on polymers with preseeding of chondrocytes and epithelial cells, (3) implant systems that are designed to induce epithelialization in vivo, (4) hybrid systems that use implants with autologous grafts, and (5) fully developed tracheal replacement matured in vitro with bioreactors. The recent developments in full trachea replacements have been reviewed elsewhere, 85 so the discussion here will be restricted to the epithelial layer.…”

Nanomaterials for cartilage tissue engineering

“…The classical tissue engineering approach is to seed isolated cells onto scaffolds and to cultivate the cell / scaffold constructs in a bioreactor ( Figure 3) and / or in the presence of stimulatory factors. Thus far, engineered cartilage constructs have unsatisfactory mechanical properties and collagen contents much less than native tissue [40,41]. For example, the flexural modulus of engineered nasal constructs is typically less than half of that of the native nasal cartilage [40].…”

“…Giardini-Rosa et al [53] developed a new method of engineering auricular cartilage constructs with structure similar to the native tissue, consisting of the cartilage zone with a single perichondrial layer on top. The lumens of trachea are lined with epithelial cells, and the lack of epithelial lining has been linked to tracheal stenosis in tissue-engineered trachea [41]. The co-culture of perichondrial and epithelial cells with chondrocytes may improve the functionality of engineered auricular and tracheal tissues.…”

Airway tissue engineering for congenital laryngotracheal disease

“…For the airway, these decellularised scaffolds offer a significant advantage over other materials in that they are closely biomimetic, retaining both macro-and microscopic architecture. Increasing evidence suggests that functional cues are also retained in the form of small molecular proteins within both tracheal and lung matrix promoting differentiation of engrafted cells [24,30,31].…”