Engineering skeletal muscle using a humanoid bioreactor platform

使用人形生物反应器平台工程骨骼肌

• 批准号: 2886432
• 金额: --
• 依托单位: University of Oxford
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2886432
• 关键词: Engineering; skeletal; muscle; using; humanoid

Skeletal muscle is the largest organ system in the body by mass and is necessary to generate forces for movement and locomotion. Unlike tendons and ligaments, muscle tissue can easily regenerate itself when subjected to minor injuries. However, irreversible loss of muscle tissue affects thousands of patients per year in the UK alone and can be caused by severe conditions such as myopathy, large trauma (e.g. blast injuries) and removal of cancer tissue. Muscle injuries and diseases are becoming more frequent as our population is aging, which causes an increasing societal and economic burden. As current repair strategies are not satisfactory, the awareness of the need for new repair approached is increasing in academia, in industry and also for end users. Tissue engineering is a promising repair strategy for skeletal muscle. This approach involves the use of biomaterials, cells and bioreactor systems, the combination of which allow control of cell culture conditions to provide physical stimulation to the cell-biomaterial constructs to engineer muscle in vitro. Both mechanical and electrical stimulation are relevant to muscle tissue engineering and have been shown to improve the improve cell proliferation and differentiation.Our research group has extensive experience of biomaterial development and testing, including use of decellularized biological tissues, hydrogels and electrospun materials. We have also recently developed a unique bioreactor system that uses a musculoskeletal humanoid robotic arm to mimic the motion and forces observed at the human shoulder joint and actuate cell-biomaterial constructs (EPSRC-funded Humanoid Bioreactor project, EP/S003509/1). Musculoskeletal humanoids can replicate the inner structures, such as muscles, tendons or bones, and the biomechanics of the human body using strings actuated by electric motors. To develop the humanoid bioreactor platform, we combined these robots with soft, flexible bioreactor chambers that host the cell-biomaterial constructs and maintain them alive for long periods of time. While our efforts have so far been focused on tendon tissue engineering for rotator cuff repair applications, the same platform can be applied to engineer skeletal muscle.This PhD project will focus on applying the humanoid bioreactor system to skeletal muscle tissue engineering. The aim is to determine the importance of physiologically-relevant mechanical stimulation and electrical stimulation for muscle tissue engineering. This will contribute to generating better quality muscle grafts. If such an approach is successful, it will provide a reliable and unlimited source of muscle autografts which would translate into safer and more cost-effective patient care.To achieve this goal, a scaffold able to support skeletal muscle tissue growth will need to be developed, either through muscle decellularization or hydrogel approaches. The existing soft chamber of the humanoid bioreactor, currently employed for tendon tissue engineering, will be adapted to host the novel muscle scaffold, allowing both its mechanical and electrical stimulation. The impact of such stimulations on the colonization of the scaffold by skeletal muscle cells will be investigated. The functionality of the engineered muscles will then need to be evaluated. This highly multidisciplinary project involves various aspects of bioengineering, biology, bioelectronics and biomechanics. Although the end application proposed here is to support the regeneration of large muscle defects, other areas in science could benefit from this project. The development of scaffold or biomaterials using this more physiological platform will be of significant interest to other researchers in the field of tissue engineering, as the strategy could be applied to other tissues. Additionally, this project will contribute to the development of bio-actuators, which would benefit developments in bio-robotics and soft robotics.

骨骼肌是人体中质量最大的器官系统，是产生运动和运动所必需的力量。与肌腱和韧带不同，肌肉组织在受到轻微损伤时可以很容易地自我再生。然而，仅在英国，每年就有数以千计的患者受到不可逆转的肌肉组织丢失的影响，而且可能是由严重的情况引起的，如肌病、大型创伤(例如冲击伤)和切除癌症组织。随着我们人口的老龄化，肌肉损伤和疾病变得更加频繁，这导致了越来越多的社会和经济负担。由于目前的维修策略并不令人满意，学术界、工业界和最终用户越来越意识到需要进行新的维修。组织工程学是一种很有前途的骨骼肌修复策略。这种方法涉及使用生物材料、细胞和生物反应器系统，它们的组合允许控制细胞培养条件，为细胞-生物材料结构提供物理刺激，以在体外工程肌肉。机械刺激和电刺激都与肌肉组织工程有关，并已被证明可以改善细胞的增殖和分化。我们的研究小组在生物材料开发和测试方面拥有丰富的经验，包括使用脱细胞生物组织、水凝胶和电纺材料。我们最近还开发了一种独特的生物反应器系统，它使用肌肉骨骼类人机械臂来模拟在人类肩关节观察到的运动和力，并驱动细胞-生物材料结构(EPSRC资助的类人生物反应器项目，EP/S003509/1)。肌肉骨骼类人可以利用电动马达驱动的弦来复制人体的内部结构，如肌肉、肌腱或骨骼，以及人体的生物力学。为了开发类人生物反应器平台，我们将这些机器人与柔软、灵活的生物反应器腔结合在一起，这些生物反应器腔容纳细胞-生物材料结构，并使它们长期存活。到目前为止，我们的努力主要集中在肌腱组织工程用于肩袖修复的应用上，同样的平台也可以应用于骨骼肌工程。这个博士项目将专注于将类人生物反应器系统应用于骨骼肌组织工程。目的是确定生理相关的机械刺激和电刺激对肌肉组织工程的重要性。这将有助于产生质量更好的肌肉移植物。如果这种方法成功，它将提供可靠和无限的自体肌肉移植来源，将转化为更安全和更具成本效益的患者护理。为了实现这一目标，需要开发一种能够支持骨骼肌组织生长的支架，无论是通过肌肉脱细胞还是通过水凝胶方法。目前用于肌腱组织工程的类人生物反应器现有的软室将被改造成容纳新型肌肉支架，允许其机械和电刺激。这种刺激对骨骼肌细胞在支架上定植的影响将被调查。然后需要对工程肌肉的功能进行评估。这个高度多学科的项目涉及生物工程、生物学、生物电子学和生物力学的各个方面。虽然这里提出的最终应用是支持大型肌肉缺陷的再生，但科学上的其他领域也可以从这个项目中受益。利用这种更具生理性的平台开发支架或生物材料将引起组织工程领域其他研究人员的浓厚兴趣，因为该策略可以应用于其他组织。此外，该项目将有助于生物执行器的开发，这将有助于生物机器人和软机器人的发展。