Optimisation of scaffold matrix for epithelial regeneration on tissue engineered airway implants.

持续创伤或需要对喉部和气管（喉或气管）进行手术的患者可能会形成不可逆的疤痕，导致严重的呼吸困难，可能危及生命。虽然传统的治疗方法能够减少疤痕并改善呼吸，但它可能会使患者无法说话或吞咽。此外，在一部分患者中，重建失败，导致严重的呼吸困难和/或需要通过手术在颈部放置永久性呼吸管。呼吸管需要患者每天雾化并需要日常维护，这对患者的生活质量会产生重大影响。此外，气管造口管可能会导致心理和社会问题。新的实验室技术的使用使得在实验室中设计新器官并将其移植到患者体内以取代受损区域成为可能。我们的团队已经证明了这项技术的可行性，通过在成人和儿童身上移植世界上第一个干细胞生长的气管来取代不可逆的狭窄。尽管取得了临床成功，但在这项技术转化为日常临床实践之前，仍存在许多障碍，即迫切需要提高移植物内部细胞的再生能力，以防止瘢痕形成，并帮助治疗咳嗽、说话和吞咽。细胞最好在蛋白质支架上生长，蛋白质支架就像地图一样指导细胞附着和分裂的位置。我的项目打算从肺中提取细胞，并将它们生长在许多不同类型的支架上，以确定哪种是最好的。这些新知识将在实验室中应用于再生更坚固的内层。通过制造一种新的内衬，可以作为干细胞气管或喉部移植的一部分，我们希望大大提高这类手术的安全性和效果，从而为英国数百名绝望的患者带来新的希望。这个项目将在伦敦大学学院（UCL）进行。伦敦大学学院是世界上最重要的生物医学研究中心之一，英国最新的研究评估活动（RAE 2008）的结果证实了这一点：2008年RAE显示，我们的研究人员进行了世界领先的研究，使伦敦大学学院跻身世界顶尖大学之列。特别是，我将作为一个已建立的多学科团队的一员工作，该团队的任务是为患病或受损的头颈部组织提供新颖的治疗方法，这将使我能够利用世界上任何其他地方都无法比拟的一系列专业知识和资源。

Patients who have sustained trauma or required surgery to the voice box and windpipe (larynx or trachea) can develop irreversible scarring leading to severe breathing difficulties that can be life threatening. Whilst conventional treatments are able to reduce scarring and improve breathing it can leave a patient unable to talk or swallow. Furthermore, in a subset of patients reconstruction fails, resulting in severe breathing difficulties and/or the need for a permanent breathing tube to be surgically placed within the neck. Breathing tubes require the patient to nebulise daily and need daily maintenance which can significantly impact on a patient's quality of life. In addition, tracheostomy tubes can be very stigmatising leading to psychological and social problems. The use of new laboratory techniques has made it possible to engineer new organs within the laboratory and transplant them into sufferers to replace the damaged area. Our group has demonstrated the viability of this technology by transplanting the world's first stem-cell grown windpipe in both an adult and a child to replace an irreversible stricture. Despite the clinical success, a number of hurdles exist before this technology can be translated to every day clinical practice, namely there is a pressing need to improve the regeneration of the cells that line the inside of the graft to prevent scarring and help with cough, speech and swallowing. Cells are best grown on protein scaffolds that act as a map to direct the cells where to attach and divide. My project intends to take cells from the lung and grow them on a number of different types of scaffold in order to determine which is the best. This new knowledge will then be applied to regenerate a more robust inner lining within the laboratory. By producing a new lining that can be used as part of a stem cell based windpipe or voice box transplant we hope to greatly improve the safety and outcome of this type of surgery and thus provide new hope to hundreds of desperate sufferers across the UK. This project will take place at University College London (UCL). UCL is amongst the world's premier centres for biomedical research, as confirmed by the results of the UK's latest research assessment exercise (RAE 2008): the numbers of our researchers shown in RAE 2008 to be carrying out world-leading research places UCL among the top universities in the world. In particularly, I will work as part of an established multidisciplinary team already tasked with providing novel therapies for diseased or damaged head and neck tissue which will allow me to draw on a range of expertise and resources unrivalled in any other part of the world.