Creation of Laryngeal Grafts from Primary Human Cells and Decellularized Laryngeal Scaffolds

Current reconstruction methods of the laryngotracheal segment fail to replace the complex functions of the human larynx. Bioengineering approaches to reconstruction have been limited by the complex tissue compartmentation of the larynx. We attempted to overcome this limitation by bio-engineering laryngeal grafts from decellularized canine laryngeal scaffolds recellularized with human primary cells under one uniform culture medium condition. First, we generated laryngeal scaffolds with preserved glycosaminoglycan content and biomechanical properties by detergent perfusion-decellularization over nine days. We proofed biocompatibility by absence of a CD3 lymphocyte response to subcutaneously implanted scaffolds in immune-competent rats. We then developed a uniform culture medium that strengthened the endothelial barrier over 5 days after an initial growth phase. Simultaneously, this culture medium supported airway epithelial cell and skeletal myoblast growth while maintaining their full differentiation and maturation potential. We then applied the uniform culture medium composition to whole laryngeal scaffolds seeded with endothelial cells from both carotid arteries and external jugular veins and generated re-endothelialized arterial and venous vascular beds. Under the same culture medium condition, we bio-engineered epithelial monolayers onto laryngeal mucosa and repopulated intrinsic laryngeal muscle. We were then able to demonstrate early muscle formation in heterotopic transplantations in immuno-deficient mice. The model supported the formation of three humanized laryngeal tissue compartments under one uniform culture condition, possibly a key factor in developing, complex, multicellular, ready-to-transplant tissue grafts

Investigating the cost-effectiveness of videotelephone based support for newly diagnosed paediatric oncology patients and their families: design of a randomised controlled trial

BACKGROUND: Providing ongoing family centred support is an integral part of childhood cancer care. For families living in regional and remote areas, opportunities to receive specialist support are limited by the availability of health care professionals and accessibility, which is often reduced due to distance, time, cost and transport. The primary aim of this work is to investigate the cost-effectiveness of videotelephony to support regional and remote families returning home for the first time with a child newly diagnosed with cancer METHODS/DESIGN: We will recruit 162 paediatric oncology patients and their families to a single centre randomised controlled trial. Patients from regional and remote areas, classified by Accessibility/Remoteness Index of Australia (ARIA+) greater than 0.2, will be randomised to a videotelephone support intervention or a usual support control group. Metropolitan families (ARIA+ ≤ 0.2) will be recruited as an additional usual support control group. Families allocated to the videotelephone support intervention will have access to usual support plus education, communication, counselling and monitoring with specialist multidisciplinary team members via a videotelephone service for a 12-week period following first discharge home. Families in the usual support control group will receive standard care i.e., specialist multidisciplinary team members provide support either face-to-face during inpatient stays, outpatient clinic visits or home visits, or via telephone for families who live far away from the hospital. The primary outcome measure is parental health related quality of life as measured using the Medical Outcome Survey (MOS) Short Form SF-12 measured at baseline, 4 weeks, 8 weeks and 12 weeks. The secondary outcome measures are: parental informational and emotional support; parental perceived stress, parent reported patient quality of life and parent reported sibling quality of life, parental satisfaction with care, cost of providing improved support, health care utilisation and financial burden for families. DISCUSSION: This investigation will establish the feasibility, acceptability and cost-effectiveness of using videotelephony to improve the clinical and psychosocial support provided to regional and remote paediatric oncology patients and their families

Topical use of MMC in the upper aerodigestive tract: a review on the side effects

Not much is known about the side effects of mitomycin C (MMC), an anti-fibrogenetic agent, in the upper aerodigestive tract. However, its use in ophthalmology is widely known and without quantitatively important side effects. A literature review was performed for side effects of MMC in the upper aerodigestive tract. Forty-six articles, describing the use of MMC to prevent scarring, were retracted from PubMed. Thirty-two are human studies. MMC is used in different concentrations (0.1–10 mg/ml) with different application times (2–5 min) and frequencies (up to 4 times). Five hundred and thirty-eight patients were included in those publications, of whom 19 developed side effects (3.53%). No side effects developed in studies, where post-application irrigation with saline was reported. The longest mean follow-up period is 75.5 months. Direct relations between the reported side effects and MMC seem absent in most studies. Serious complications seem to occur when MMC is used in high concentrations. Unfortunately, sometimes crucial information is lacking. One patient was described who supposedly developed laryngeal carcinoma after repeated treatment of hyperkeratosis and anterior commissure webbing. Animal studies show that excessive fibrin production can lead to acute airway obstruction. In conclusion, topical application of MMC on a wound with consecutive irrigation with saline can be performed safely to prevent scar formation in circular structures of the upper aerodigestive tract. Long-term yearly control of the application site seems advisable