Development and clinical translation of tubular constructs for tracheal tissue engineering: a review

Effective restoration of extensive tracheal damage arising from cancer, stenosis, infection or congenital abnormalities remains an unmet clinical need in respiratory medicine. The trachea is a 10–11 cm long fibrocartilaginous tube of the lower respiratory tract, with 16–20 tracheal cartilages anterolaterally and a dynamic trachealis muscle posteriorly. Tracheal resection is commonly offered to patients suffering from short-length tracheal defects, but replacement is required when the trauma exceeds 50% of total length of the trachea in adults and 30% in children. Recently, tissue engineering (TE) has shown promise to fabricate biocompatible tissue-engineered tracheal implants for tracheal replacement and regeneration. However, its widespread use is hampered by inadequate re-epithelialisation, poor mechanical properties, insufficient revascularisation and unsatisfactory durability, leading to little success in the clinical use of tissue-engineered tracheal implants to date. Here, we describe in detail the historical attempts and the lessons learned for tracheal TE approaches by contextualising the clinical needs and essential requirements for a functional tracheal graft. TE manufacturing approaches explored to date and the clinical translation of both TE and non-TE strategies for tracheal regeneration are summarised to fully understand the big picture of tracheal TE and its impact on clinical treatment of extensive tracheal defects.

The Histology of the Trachea in Dogs

The trachea was collected from apparently normal six adult dogs of spitz breed aged between 2-4 years of age from the post-mortem of the Veterinary Pathology department. The aim of the study was to observe the histological details of the trachea in the spitz breed of dogs. The tracheal wall consisted of the mucosa, submucosa, hyaline cartilage, and adventitia. Tracheal mucosa was lined by a pseudostratified ciliated columnar epithelium with mucous secreting goblet cell and basal cells. Lamina propria was made up of loose connective tissue and contained some alveolar mucous glands. Muscularis mucosa was a thin layer with smooth muscle fibers arranged in a dispersed manner. The submucosa contained loose connective tissue with numerous mucous secreting tubule – acinar submucosal gland and was found related to the perichondrium of cartilaginous rings. The dense fibroelastic tissue was found between the cartilaginous rings. The cartilaginous rings were flattened in cross-section. Thin tunica adventitia of loose connective tissue and covered the cartilaginous rings. Trachealis muscle was found.

Laryngotracheal Separation Following Blunt Neck Injury

Blunt laryngotracheal injuries are rare. The signs and symptoms of blunt laryngotracheal trauma are not always specific to the extent or type of injury. A high index of suspicion should exist in any injury that may be associated with airway trauma. We report a 30-years man who had progressive shortness of breath following blunt neck injury. He had massive emphysema whereby an emergency tracheostomy with multiple fasciotomy was performed. During emergency tracheostomy, it was noted that he had anterior cricotracheal separation which was communicated posteriorly by mucosa and trachealis muscle. Bangladesh J Otorhinolaryngol; October 2016; 22(2): 114-118

Low Profile Airway Stent

Tracheobronchomalacia (TBM) is a condition where the trachealis muscle is too weak to withstand the pressure difference between the outer and inner walls of the trachea. This causes the airway to narrow or collapse. Patients with TBM may have symptoms including coughing, wheezing, and/or difficulty in breathing. There are current treatments available but each one has their own limitations and complications. Such complications of current commercially available airway stents are migration, breakage, and mucus build-up. The team has developed a unique airway stent that potentially has fewer complications called the Low Profile Airway Stent. It is a thin, metal zig-zag shaped wire that will be anchored parallel to the trachealis muscle to prevent trachea narrowing and collapsing. The Low Profile Airway Stent will not fully cover the cilia in the trachea which reduces mucus build-up. The stent will also be anchored to the walls of the trachea which will prevent migration. The team is still in the process of developing an anchoring method and delivery device for the stent.

Mucus secretion from individual submucosal glands of the ferret trachea

Mucus secretion from individual tracheal glands in adult ferrets was studied with time-lapse optical imaging of mucus droplets under an oil layer. Density of functional glands (determined by responses to 1 μM carbachol) was 1.5 ± 0.3 per mm2 ( n = 6). Secretion rates (in pl·min−1·gland−1) were as follows: 4.1 ± 0.7 basal (unstimulated; n = 27, 669 glands), 338 ± 70 to 10 μM forskolin ( n = 8, 90 glands), 234 ± 13 to 1 μM VIP ( n = 6, 57 glands), 183 ± 92 to 10 μM isoproterenol ( n = 3, 33 glands), 978 ± 145 to 1 μM carbachol ( n = 11, 131 glands), and 1,348 ± 325 to 10 μM phenylephrine ( n = 7, 74 glands). The potency (EC50, in μM) and efficacy ( Vmax, in pl·min−1·gland−1) were 7.6 (EC50) and 338 ± 16 ( Vmax) to forskolin, 1.0 (EC50) and 479 ± 19 ( Vmax) to VIP, 0.6 (EC50) and 1,817 ± 268 ( Vmax) to carbachol, and 3.7 (EC50) and 1,801 ± 95 ( Vmax) to phenylephrine. Although carbachol and phenylephrine were equally effective secretagogues, only carbachol caused contractions of the trachealis muscle. Synergy was demonstrated between 300 nM isoproterenol and 100 nM carbachol, which, when combined, produced a secretion rate almost fourfold greater than predicted from their additive effect. The dependence of fluid secretion on Cl− and HCO3− varied depending on the mode of stimulation. Secretion stimulated by VIP or forskolin was reduced by ∼60% by blocking either anion, while carbachol-stimulated secretion was blocked 68% by bumetanide and only 32% by HEPES replacement of HCO3−. These results provide parametric data for comparison with fluid secretion from glands in ferrets lacking CFTR.