MechAscan - A novel online mechanical assessment tool for manufacturing engineered tissues in regenerative medicine and drug discovery.

由于预期寿命的延长，世界各地60岁以上人口的比例比任何其他年龄段的人增长得都快。人口老龄化可以被视为公共卫生政策和社会经济发展的一个成功故事，但它对医学和英国国民健康保险制度提出了挑战，以最大限度地提高老年人的健康和功能能力。再生医学是这种更长寿和健康生活方式的潜在解决方案，它提供了基于细胞的治疗方法，可以取代受损或患病的组织。不断增长的替代组织带来了令人兴奋的新解决方案，现在需要新的制造方法和工艺才能将其移植到临床上。生物反应器是一种机械装置，它为工程组织提供受控的生长环境，并模拟细胞和组织在体内经历的物理力量。在培养过程中和植入到患者体内之前，监测组织植入物的成熟度，对于确定最佳制造标准和临床成功非常重要。组织工程植入物必须表现出的关键特性包括强度和耐久性。为了从成像中推断材料的特性，需要新的非破坏性的三维成像技术，这种技术可以在制造现场和临床上有效地提供准确的结果。在这份提案中，我们的合作伙伴将成像技术光学相干弹性成像与流体静压生物反应器相结合，创建了一种新型成像解决方案MechAscan，该解决方案可以对工程化组织植入物进行实时机械表征和同步物理刺激。与目前可用的传统机械测试方法和弹性成像技术相比，MechAscan将提供明显的优势，后者需要机械载荷与样品直接接触，并且具有破坏性。此外，MechAscan可用于在无菌生长环境中的培养中生长时对机械性能进行实时监控。我们的目标是开发一种新的技术平台，能够在无菌生长环境中实时和无损地监测组织工程产品，以避免在制造过程中构建变异，并允许将具有已知特性的再生医学构建转化为临床。为了促进该技术的应用并将其转化为临床，我们建议以一种结合了生物反应器技术、生物材料科学、物理和数学的跨学科方法来全面测试和验证MechAscan技术。

The proportion of people around the world aged over 60 years is growing faster than any other age group, as a result of longer life expectancy. This population ageing can be seen as a success story for public health policies and for socioeconomic development, but it places a challenge on medicine and, within the UK, the NHS to maximize the health and functional capacity of older people. Regenerative Medicine is one potential solution for this longer life and healthy lifestyle, providing cell based therapies which can replace damaged or diseased tissues. Growing replacement tissues is bringing exciting novel solutions which now require new manufacturing methods and processes to enable the translation to the clinic. Bioreactors are mechanical devices that provide controlled growth environments for engineered tissues and mimic the physical forces cells and tissues experience in the body. Monitoring the maturation of tissue implants during culture, and prior to implantation into the patient, is important for defining optimum manufacturing criteria and for their clinical success. Key properties that tissue engineered implants must display include strength and durability. To infer material properties from imaging, new non-destructive, three-dimensional imaging techniques are needed, that can be used to provide accurate results efficiently at both the manufacturing site and the clinic. In this proposal, our partners have linked the imaging technique, optical coherence elastography, with a hydrostatic pressure bioreactor to create a novel imaging solution, MechAscan, which allows real-time mechanical characterisation and simultaneous physical stimulation of engineered tissue implants. MechAscan will provide a clear advantage over currently available traditional mechanical testing approaches and elastography techniques, which require direct contact of the mechanical load with the sample and are destructive. Additionally, MechAscan can be used for real-time monitoring of mechanical properties as the construct is grown in culture in a sterile growth environment. Our aim is to develop a novel technology platform allowing real-time and non-destructive monitoring of tissue engineered products in a sterile growth environment to avoid construct to construct variation during manufacturing and allow the translation of regenerative medicine constructs with known properties into the clinic. To facilitate uptake in use of the technology and translation to the clinic, we propose to fully test and validate the MechAscan technology in an interdisciplinary approach combining bioreactor technology, biomaterials science, physics and mathematics.