Developing a humanoid bioreactor for tendon tissue engineering

肌腱疾病和其他肌肉骨骼疾病一样，随着我们人口的老龄化，代表着越来越大的社会和经济负担。它们通常会导致流泪，导致疼痛和残疾。手术修复的速度越来越快，但患者的结果并不乐观，40%的肩关节修复失败是由于组织愈合不良。主要组织丢失的患者康复的机会特别小。一种有前景的修复策略是使用工程化肌腱移植物。组织工程学涉及开发生物反应器，利用患者的细胞、支架和机械刺激在体外产生肌腱组织。然而，需要更先进的生物反应器来提供功能性肌腱移植物。目前的生物反应器大多提供单轴循环载荷，而有证据表明，它们应该提供与生理上发现的类似的多轴应力。在这种背景下，肌肉骨骼类人机器人具有施加现实压力的潜力。这些机器人复制人体的内部结构，如肌肉、肌腱和骨骼。近年来，它们已经取得了重大进展，现在可以考虑将它们用于尚未探索的医学应用。本研究项目的目的是探索利用肌肉骨骼类人机器人作为肌肉骨骼组织工程，特别是肌腱工程的平台的潜力。总体假设是，类人机器人将能够提供生理机械刺激，因此，它们将导致工程化肌腱比目前拉伸生物反应器生产的肌腱更具功能性。为了证明这一点，我们建议：(1)设计一种与肌肉骨骼类人相适应的灵活的生物反应器小室，(2)使现有的类人肩适应肌腱工程应用，(3)基于肩部康复练习确定类人生物反应器的加载方式，(4)利用新系统生产肌腱结构，并展示与现有生物反应器相比的改进。将使用计算建模和运动分析来支持我们的工作。这一开创性的项目是朝着功能性和个性化移植物迈出的一步，以改善患者的预后并降低社会成本。

Tendon diseases, like other musculoskeletal disorders, represent a growing social and economic burden as our population is aging. They often result in tears, causing pain and disability. Surgical repairs are performed at an increasing rate but patient's outcomes are not promising, with 40% of repairs failing at the shoulder joint due to poor tissue healing. Patients with major tissue loss have particularly little chances of recovering. A promising repair strategy is the use of engineered tendon grafts. Tissue engineering involves the development of bioreactors that generate tendon tissue in vitro using the patient's cells, scaffolds and mechanical stimulation. However, more advanced bioreactors are needed to provide functional tendon grafts. Current bioreactors mostly provide uniaxial cyclic loadings, while evidence suggests that they should provide multiaxial stresses, similar to those found physiologically. In this context, musculoskeletal humanoid robots have the potential to apply realistic stresses. These robots replicate the inner structures of the human body such as muscles, tendons and bones. They have seen major developments in recent years, making it now possible to consider their use for unexplored applications in medicine. The aim of this research project is to investigate the potential of using musculoskeletal humanoid robots as a platform for musculoskeletal tissue engineering and in particular for tendon engineering. The overall hypothesis is that humanoid robots will enable the provision of physiological mechanical stimulation and that, as a result, they will lead to engineered tendons that are more functional than those produced with current stretch bioreactors. To demonstrate this, we are proposing to: (1) design a flexible bioreactor chamber compatible with musculoskeletal humanoids, (2) adapt an existing humanoid shoulder for our tendon engineering applications, (3) define the loading regimes of the humanoid bioreactor based on shoulder rehabilitation exercises, (4) produce tendon constructs with the novel system and demonstrate improvements compared to current bioreactors. Computational modelling and motion analysis will be used to support our work. This pioneering project is a step towards functional and personalised grafts to improve patient outcomes and reduce costs to the society.