Tissue-Engineered Larynx: Future Applications in Laryngeal Cancer

PURPOSE OF REVIEW: This article reviews the latest developments in tissue engineering for the larynx with a specific focus on the treatment of laryngeal cancer. RECENT FINDINGS: Challenges in tissue engineering a total larynx can be divided into scaffold design, methods of re-mucosalization, and how to restore laryngeal function. The literature described a range of methods to deliver a laryngeal scaffold including examples of synthetic, biomimetic, and biological scaffolds. Methods to regenerate laryngeal mucosa can be divided into examples that use a biological dressing and those that engineer a new mucosal layer de novo. Studies aiming to restore laryngeal function have been reported, but to date, the optimum method for achieving this as part of a total laryngeal transplant is yet to be determined. SUMMARY: There is great potential for tissue engineering to improve the treatments available for laryngeal cancer within the next 10 years. A number of challenges exist however and advances in restoring function must keep pace with developments in scaffold design

3D bioprinting for tissue engineering: Stem cells in hydrogels

Surgical limitations require alternative methods of repairing and replacing diseased and damaged tissue. Regenerative medicine is a growing area of research with engineered tissues already being used successfully in patients. However, the demand for such tissues greatly outweighs the supply and a fast and accurate method of production is still required. 3D bioprinting offers precision control as well as the ability to incorporate biological cues and cells directly into the material as it is being fabricated. Having precise control over scaffold morphology and chemistry is a significant step towards controlling cellular behaviour, particularly where undifferentiated cells, i.e., stem cells, are used. This level of control in the early stages of tissue development is crucial in building more complex systems that morphologically and functionally mimic in vivo tissue. Here we review 3D printing hydrogel materials for tissue engineering purposes and the incorporation of cells within them. Hydrogels are ideal materials for cell culture. They are structurally similar to native extracellular matrix, have a high nutrient retention capacity, allow cells to migrate and can be formed under mild conditions. The techniques used to produce these materials, as well as their benefits and limitations, are outlined

Tissue Engineered Airways: A Prospects Article

An ideal tracheal scaffold must withstand luminal collapse yet be flexible, have a sufficient degree of porosity to permit vascular and cellular ingrowth, but also be airtight and must facilitate growth of functional airway epithelium to avoid infection and aid in mucocilliary clearance. Finally, the scaffold must also be biocompatible to avoid implant rejection. Over the last 40 years, efforts to design and manufacture the airway have been undertaken worldwide but success has been limited and far apart. As a result, tracheal resection with primary repair remains the Gold Standard of care for patients presenting with airway disorders and malignancies. However, the maximum resectable length of the trachea is restricted to 30% of the total length in children or 50% in adults. Attempts to provide autologous grafts for human application have also been disappointing for a host of different reasons, including lack of implant integration, insufficient donor organs and poor mechanical strength resulting in an unmet clinical need. The two main approaches researchers have taken to address this issue have been the development of synthetic scaffolds and the use of decellularised organs. To date, a number of different decellularisation techniques and a variety of materials, including polyglycolic acid (PGA) and nanocomposite polymers have been explored. The findings thus far have shown great promise, however there remain a significant number of caveats accompanying each approach. That being said, the possibilities presented by these two approaches could be combined to produce a highly successful, clinically viable hybrid scaffold. This article aims to highlight advances in airway tissue engineering and provide an overview of areas to explore and utilise in accomplishing the aim of a developing an ideal tracheal prosthesis

The Host Immune Response to Tissue-Engineered Organs: Current Problems and Future Directions

As the global health burden of chronic disease increases, end-stage organ failure has become a costly and intractable problem. De novo organ creation is one of the long-term goals of the medical community. One of the promising avenues is that of tissue engineering: the use of biomaterials to create cells, structures, or even whole organs. Tissue engineering has emerged from its nascent stage, with several proof-of-principle trials performed across various tissue types. As tissue engineering moves from the realm of case trials to broader clinical study, three major questions have emerged: (1) Can the production of biological scaffolds be scaled up accordingly to meet current and future demands without generating an unfavorable immune response? (2) Are biological scaffolds plus or minus the inclusion of cells replaced by scar tissue or native functional tissue? (3) Can tissue-engineered organs be grown in children and adolescents given the different immune profiles of children? In this review, we highlight current research in the immunological response to tissue-engineered biomaterials, cells, and whole organs and address the answers to these questions

Optimized isolation and expansion of human airway epithelial basal cells from endobronchial biopsy samples

Autologous airway epithelial cells have been used in clinical tissue-engineered airway transplantation procedures with a view to assisting mucosal regeneration and restoring mucociliary escalator function. However, limited time is available for epithelial cell expansion due to the urgent nature of these interventions and slow epithelial regeneration has been observed in patients. Human airway epithelial cells can be expanded from small biopsies or brushings taken during bronchoscopy procedures but the optimal mode of tissue acquisition from patients has not been investigated. Here, we compare endobronchial brushing and endobronchial biopsy samples in terms of their cell number and their ability to initiate basal epithelial stem cell cultures. We found that direct co-culture of samples with 3T3-J2 feeder cells in culture medium containing a Rho-associated protein kinase (ROCK) inhibitor, Y-27632, led to the selective expansion of greater numbers of basal epithelial stem cells during the critical early stages of culture than traditional techniques. Additionally, we established the benefit of initiating cell cultures from cell suspensions, either using brushing samples or through enzymatic digestion of biopsies, over explant culture. Primary epithelial cell cultures were initiated from endobronchial biopsy samples that had been cryopreserved prior to the initiation of cell cultures, suggesting that cryopreservation could eliminate the requirement for close proximity between the clinical facility in which biopsy samples are taken and the specialist laboratory in which epithelial cells are cultured. Overall, our results suggest ways to expedite epithelial cell preparation in future airway cell therapy or bioengineered airway transplantation procedures

Older adults experiences of rehabilitation in acute health care

Rehabilitation is a key component of nursing and allied healthcare professionals’ roles in most health and social care settings. This paper reports on stage 2 of an action research project to ascertain older adult's experience of rehabilitation. Twenty postdischarge interviews were conducted and the interview transcripts were analysed using thematic content analysis. All older adults discharged from an acute older acute rehabilitation ward to their own homes in the community were eligible to participate. The only exclusion criterion was older adults who were thought to be unable to give consent to participate by the nurse in charge and the researcher. Whilst 92 older adults were eligible to participate in this research study, only 20 were interviewed. The findings from this study suggest that older adults valued communication with health professionals but were aware of their time constraints that hindered communication. This study suggests that both nurses and allied health professionals are not actively providing rehabilitative services to promote health and well-being, which contradicts the focus of active ageing. Furthermore, there was evidence of unmet needs on discharge, and older adults unable to recall the professions that were involved in their interventions and the rationale for therapy input. It is suggested that further research is needed to explore the effectiveness of allied health rehabilitation in the acute setting. This study highlights the need for further research into older adults’ perceptions of the rehabilitation process in the acute setting

Autologous Cell Seeding in Tracheal Tissue Engineering

Purpose of Review: There is no consensus on the best technology to be employed for tracheal replacement. One particularly promising approach is based upon tissue engineering and involves applying autologous cells to transplantable scaffolds. Here, we present the reported pre-clinical and clinical data exploring the various options for achieving such seeding. Recent Findings: Various cell combinations, delivery strategies, and outcome measures are described. Mesenchymal stem cells (MSCs) are the most widely employed cell type in tracheal bioengineering. Airway epithelial cell luminal seeding is also widely employed, alone or in combination with other cell types. Combinations have thus far shown the greatest promise. Chondrocytes may improve mechanical outcomes in pre-clinical models, but have not been clinically tested. Rapid or pre-vascularization of scaffolds is an important consideration. Overall, there are few published objective measures of post-seeding cell viability, survival, or overall efficacy. Summary: There is no clear consensus on the optimal cell-scaffold combination and mechanisms for seeding. Systematic in vivo work is required to assess differences between tracheal grafts seeded with combinations of clinically deliverable cell types using objective outcome measures, including those for functionality and host immune response

Feasibility of vocal fold abduction and adduction assessment using cine-MRI

OBJECTIVE: Determine feasibility of vocal fold (VF) abduction and adduction assessment by cine magnetic resonance imaging (cine-MRI) METHODS: Cine-MRI of the VF was performed on five healthy and nine unilateral VF paralysis (UVFP) participants using an axial gradient echo acquisition with temporal resolution of 0.7 s. VFs were continuously imaged with cine-MRI during a 10-s period of quiet respiration and phonation. Scanning was repeated twice within an individual session and then once again at a 1-week interval. Asymmetry of VF position during phonation (VF phonation asymmetry, VFPa) and respiration (VF respiration asymmetry, VFRa) was determined. Percentage reduction in total glottal area between respiration and phonation (VF abduction potential, VFAP) was derived to measure overall mobility. An un-paired t-test was used to compare differences between groups. Intra-session, inter-session and inter-reader repeatability of the quantitative metrics was evaluated using intraclass correlation coefficient (ICC). RESULTS: VF position asymmetry (VFPa and VFRa) was greater (p=0.012; p=0.001) and overall mobility (VFAP) was lower (p=0.008) in UVFP patients compared with healthy participants. ICC of repeatability of all metrics was good, ranged from 0.82 to 0.95 except for the inter-session VFPa (0.44). CONCLUSION: Cine-MRI is feasible for assessing VF abduction and adduction. Derived quantitative metrics have good repeatability. KEY POINTS: • Cine-MRI is used to assess vocal folds (VFs) mobility: abduction and adduction. • New quantitative metrics are derived from VF position and abduction potential. • Cine-MRI able to depict the difference between normal and abnormal VF mobility. • Cine-MRI derived quantitative metrics have good repeatability

Laryngological presentations and patient-reported outcome measures in Ehlers-Danlos syndrome

OBJECTIVE: This study aimed to characterise the laryngological presentations of Ehlers–Danlos syndrome and conduct a preliminary exploration of patient-reported outcome measures. METHODS: This paper describes a retrospective case series of patients with Ehlers–Danlos syndrome seen by the senior author between 2005 and 2019. A literature review was conducted to summarise the existing findings. RESULTS: Twenty-one patients met the inclusion criteria. All reported symptoms were grouped; this showed that swallowing, voice and hyolaryngeal skeletal complex problems were commonest. Patient-reported outcome measures were available for eight patients, which showed large variations in: the Reflux Severity Index (median = 25.5; range = 0–33), Eating Assessment Tool score (median = 21.5; range = 0–35) and Voice Handicap Index (median = 21.5; range = 0–104). Twelve studies met our literature review inclusion criteria, involving at least 91 patients with laryngological presentations of Ehlers–Danlos syndrome. CONCLUSION: Ehlers–Danlos syndrome patients experience musculoskeletal issues, which in the throat manifest as hyolaryngeal skeletal complex problems. Future studies with larger patient numbers are required to validate laryngological patient-reported outcome measure tools in Ehlers–Danlos syndrome