Translational development of a 3D bioactive nerve conduit for peripheral nerve repair, through application of topographical cues and stem cell support

通过应用地形线索和干细胞支持，转化开发用于周围神经修复的 3D 生物活性神经导管

• 批准号: MR/L017741/1
• 负责人: Suzanne Thomson
• 金额: $ 26.15万
• 依托单位: University of Glasgow
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2014
• 资助国家: 英国
• 起止时间: 2014 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FL017741%2F1
• 关键词: Translational; development; 3D; bioactive; nerve

Using Biotechnology to Improve the Outcome Following Devastating Nerve Injuries Major nerve injuries can occur during birth, from accidental trauma, or as the result of cancer treatments. Unfortunately they are common (1-2 people in every 1000 each year), mainly affect young patients, and cause permanent disability. Many patients never return to gainful employment and all suffer long and painful recovery times. These injuries rank alongside cerebral palsy and spinal injury in terms of disability, and the effect on the lives of patients and their families. This in turn translates as a significant economic cost to society, both through medical interventions and loss of active members of workforce population. Furthermore, nerve repair limits what can be achieved with face or hand transplantation, and prevents useful transplantation of voiceboxes or legs, as the rate of healing is much slower and less successful than that of other types of tissue (e.g. skin/bone).Reconstructive microsurgeons can repair damaged nerves, but even under the best circumstances many nerve fibres fail to cross the site of surgical repair or grow back to give function. If the damaged segment of the nerve is more than 1cm long, a sensory nerve must be borrowed from elsewhere in the body to bridge the gap, this causes scarring and permanent numbness at the donor site where this is taken from. Recovery is always very slow (~18 months), painful, and inadequate, since <50% of nerve cells actually regrow through traditional nerve repairs. It is vital that we discover what controls nerve healing and it is well recognised that we need to develop new technologies to improve surgical outcomes for these patients. Promising work is underway at the University of Glasgow and it's collaborating laboratories on this important topic.Recent scientific advances in laboratory petri-dishes demonstrate that nerves heal better if the contour (topography) of the surface on they're growing on has tiny grooves to guide them - that knowledge has been applied to make tiny patterned tubes to use to direct the growth of repaired nerves. The tubes could also be used to deliver other useful treatments that will help the nerve fibres to grow better - for example a lot of research has been done by our laboratories and others, to show that stem cells taken from patient's fat (removed by liposuction), or safe drug treatments will also improve biological conditions for nerve healing. This project will combine these developments into a 3-D tube (conduit), that will be used to repair damaged nerves. The research will be undertaken at the world class research facilities in the Centre for Cell Engineering, University of Glasgow, and our partner laboratory in Sweden with detailed input from international experts (surgeons and scientists) in the field of nerve repair. By combining guidance cues, stem cells and drug treatments we believe we can enhance nerve healing, and improve quality of life for patients in the future. Clinical applications of this exciting biotechnology are widespread and include nerve injury following civilian/military trauma, cancer treatments, birth injury, and face, limb, or voicebox transplants.

使用生物技术改善毁灭性神经损伤后的结局主要神经损伤可能发生在分娩期间、意外创伤或癌症治疗的结果。不幸的是，它们很常见(每年每1000人中有1-2人)，主要影响年轻患者，并导致永久性残疾。许多患者再也没有回到有收入的工作岗位，所有人都经历了漫长而痛苦的康复时间。就伤残程度及其对患者及其家人生活的影响而言，这些损伤与脑瘫和脊柱损伤并列。这反过来又会通过医疗干预和劳动力人口中活跃成员的流失，转化为社会的重大经济成本。此外，神经修复限制了面部或手移植所能达到的效果，并阻止了有用的声箱或腿部移植，因为愈合速度比其他类型的组织(如皮肤/骨骼)慢得多，也不太成功。重建显微外科医生可以修复受损的神经，但即使在最好的情况下，许多神经纤维也无法穿过手术修复的部位或重新生长以发挥功能。如果受损神经的长度超过1厘米，必须从身体其他部位借用感觉神经来弥合缺口，这会在供体部位造成疤痕和永久性麻木。恢复总是非常缓慢(约18个月)、痛苦和不充分，因为50%的神经细胞实际上是通过传统的神经修复重新生长的。我们发现控制神经愈合的因素是至关重要的，人们普遍认为我们需要开发新技术来改善这些患者的手术结果。格拉斯哥大学及其合作实验室正在就这一重要课题开展有希望的工作。实验室培养皿的最新科学进展表明，如果神经生长在表面的轮廓(地形)上有微小的凹槽来引导它们，神经就会愈合得更好--这一知识已经被用来制造微小的有图案的管，用来指导修复后的神经的生长。这些管子还可以用来提供其他有用的治疗方法，帮助神经纤维更好地生长-例如，我们的实验室和其他人已经做了大量研究，表明从患者脂肪中提取的干细胞(通过抽脂去除)或安全的药物治疗也将改善神经愈合的生物条件。这个项目将把这些发展结合到一个3D管(导管)中，用于修复受损的神经。这项研究将在格拉斯哥大学细胞工程中心的世界级研究设施和我们在瑞典的合作实验室进行，神经修复领域的国际专家(外科医生和科学家)将提供详细的意见。通过将指导线索、干细胞和药物治疗相结合，我们相信我们可以促进神经愈合，并改善患者未来的生活质量。这一令人兴奋的生物技术的临床应用非常广泛，包括平民/军事创伤后的神经损伤、癌症治疗、分娩损伤以及面部、肢体或语音盒移植。

项目成果

Developing 3D interfaces to aid nerve repair

开发 3D 界面以帮助神经修复

• DOI: 10.3389/conf.fbioe.2016.01.02605
• 发表时间: 2016
• 期刊: Frontiers in Bioengineering and Biotechnology
• 影响因子: 5.7
• 作者: Suzanne T

The introduction of plastic and reconstructive surgery to the University of Glasgow undergraduate medical core curriculum.

将整形与重建外科引入格拉斯哥大学本科医学核心课程。

• DOI: 10.1136/postgradmedj-2019-137046
• 发表时间: 2020
• 期刊: Postgraduate medical journal
• 影响因子: 5.1
• 作者: Higgins G

Commentary to accompany the paper: The quality of systematic reviews addressing peripheral nerve repair and reconstruction.

该论文的评论：关于周围神经修复和重建的系统评价的质量。

• DOI: 10.1016/j.bjps.2018.11.012
• 发表时间: 2019
• 期刊: JPRAS
• 作者: Thomson S

Anatomically accurate 3D modelling and printing in a case of obstetric brachial plexus injury.

产科臂丛神经损伤病例的解剖学精确 3D 建模和打印。

• DOI: 10.1016/j.jpra.2020.02.003
• 发表时间: 2020
• 期刊: JPRAS open
• 影响因子: 1.4
• 作者: Higgins GC

Microtopographical cues promote peripheral nerve regeneration via transient mTORC2 activation.

• DOI: 10.1016/j.actbio.2017.07.031
• 发表时间: 2017-09-15
• 期刊: Acta biomaterialia
• 影响因子: 9.7
• 作者: Thomson SE;Charalambous C;Smith CA;Tsimbouri PM;Déjardin T;Kingham PJ;Hart AM;Riehle MO
• 通讯作者: Riehle MO